Obstetrics

Nearly 4 years after a woman ended an unwanted pregnancy with abortion pills obtained at a Phoenix clinic, she finds herself mired in an ongoing lawsuit over that decision.

A judge allowed the woman’s ex-husband to establish an estate for the embryo, which had been aborted in its seventh week of development. The ex-husband filed a wrongful death lawsuit against the clinic and its doctors in 2020, alleging that physicians failed to obtain proper informed consent from the woman as required by Arizona law.

Across the United States, people have sued for negligence in the death of a fetus or embryo in cases where a pregnant person has been killed in a car crash or a pregnancy was lost because of alleged wrongdoing by a physician. But a court action claiming the wrongful death of an aborted embryo or fetus is a more novel strategy, legal experts said.

The experts said this rare tactic could become more common, as anti-abortion groups have signaled their desire to further limit reproductive rights following the U.S. Supreme Court’s decision in Dobbs v. Jackson Women’s Health Organization, which overturned Roe v. Wade. The Arizona lawsuit and others that may follow could also be an attempt to discourage and intimidate providers and harass plaintiffs’ former romantic partners, experts said.

Lucinda Finley, a law professor at the University at Buffalo who specializes in tort law and reproductive rights, said the Arizona case is a “harbinger of things to come” and called it “troubling for the future.”

Ms. Finley said she expects state lawmakers and anti-abortion groups to use “unprecedented strategies” to try to prevent people from traveling to obtain abortions or block them from obtaining information on where to seek one.

Perhaps the most extreme example is in Texas, where the Texas Heartbeat Act, signed into law in May 2021 and upheld by the U.S. Supreme Court in December, allows private citizens to sue a person who performs or aids in an abortion.

“It’s much bigger than these wrongful death suits,” Ms. Finley said.

Civia Tamarkin, president of the National Council of Jewish Women Arizona, which advocates for reproductive rights, said the Arizona lawsuit is part of a larger agenda that anti-abortion advocates are working toward.

“It’s a lawsuit that appears to be a trial balloon to see how far the attorney and the plaintiff can push the limits of the law, the limits of reason, the limits of science and medicine,” Ms. Tamarkin said.

In July 2018, the ex-husband, Mario Villegas, accompanied his then-wife to three medical appointments – a consultation, the abortion, and a follow-up. The woman, who ProPublica is not identifying for privacy reasons, said in a deposition in the wrongful death suit that at the time of the procedure the two were already talking about obtaining a divorce, which was finalized later that year.

“We were not happy together at all,” she said.

Mr. Villegas, a former Marine from Globe, Ariz., a mining town east of Phoenix, had been married twice before and has other children. He has since moved out of state.

In a form his then-wife filled out at the clinic, she said she was seeking an abortion because she was not ready to be a parent and her relationship with Mr. Villegas was unstable, according to court records. She also checked a box affirming that “I am comfortable with my decision to terminate this pregnancy.” The woman declined to speak on the record with ProPublica out of fear for her safety.

The following year, in 2019, Mr. Villegas learned about an Alabama man who hadn’t wanted his ex-girlfriend to have an abortion and sued the Alabama Women’s Center for Reproductive Alternatives in Huntsville on behalf of an embryo that was aborted at six weeks.

To sue on behalf of the embryo, the would-be father, Ryan Magers, went to probate court where he asked a judge to appoint him as the personal representative of the estate. In probate court, a judge may appoint someone to represent the estate of a person who has died without a will. That representative then has the authority to distribute the estate’s assets to beneficiaries.

When Mr. Magers filed to open an estate for the embryo, his attorney cited various Alabama court rulings involving pregnant people and a 2018 amendment to the Alabama Constitution recognizing the “sanctity of unborn life and the rights of unborn children.”

A probate judge appointed Mr. Magers representative of the estate, giving him legal standing to sue for damages in the wrongful death claim. The case, believed to be the first instance in which an aborted embryo was given legal rights, made national headlines.

It’s unclear how many states allow an estate to be opened on behalf of an embryo or fetus. Some states, like Arizona, don’t explicitly define what counts as a deceased person in their probate code, leaving it to a judge to decide. In a handful of states, laws define embryos and fetuses as a person at conception, which could allow for an estate, but it’s rare.

An Alabama circuit court judge eventually dismissed Mr. Magers’ wrongful death lawsuit, stating that the claims were “precluded by State and Federal laws.”

Mr. Villegas contacted Mr. Magers’ attorney, Brent Helms, about pursuing a similar action in Arizona and was referred to J. Stanley Martineau, an Arizona attorney who had flown to Alabama to talk to Mr. Helms about Mr. Magers’ case.

In August 2020, Mr. Villegas filed a petition to be appointed personal representative of the estate of “Baby Villegas.” His ex-wife opposed the action and contacted a legal advocacy organization focused on reproductive justice, which helped her obtain a lawyer.

In court filings, Mr. Villegas said he prefers to think of “Baby Villegas” as a girl, although the sex of the embryo was never determined, and his lawyer argued that there isn’t an Arizona case that explicitly defines a deceased person, “so the issue appears to be an open one in Arizona.”

In a 2021 motion arguing for dismissal, the ex-wife’s attorney, Louis Silverman, argued that Arizona’s probate code doesn’t authorize the appointment of a personal representative for an embryo, and that granting Mr. Villegas’ request would violate a woman’s constitutional right to decide whether to carry a pregnancy to term.

“U.S. Supreme Court precedent has long protected the constitutional right of a woman to obtain an abortion, including that the decision whether to do so belongs to the woman alone – even where her partner, spouse, or ex-spouse disagrees with that decision,” Mr. Silverman said last year.

Gila County Superior Court Judge Bryan B. Chambers said in an order denying the motion that his decision allows Mr. Villegas to make the argument that the embryo is a person in a wrongful death lawsuit, but that he has not reached that conclusion at this stage. Mr. Villegas was later appointed the personal representative of the estate.

As states determine what is legal in the wake of Dobbs and legislators propose new abortion laws, anti-abortion groups such as the National Right to Life Committee see civil suits as a way to enforce abortion bans and have released model legislation they hope sympathetic legislators will duplicate in statehouses nationwide.

“In addition to criminal penalties and medical license revocation, civil remedies will be critical to ensure that unborn lives are protected from illegal abortions,” the group wrote in a June 15 letter to its state affiliates that included the model legislation.

James Bopp Jr., general counsel for the committee, said in an interview with ProPublica that such actions will be necessary because some “radical Democrat” prosecutors have signaled they won’t enforce criminal abortion bans. Last month, 90 prosecutors from across the country indicated that they would not prosecute those who seek abortions.

“The civil remedies follow what the criminal law makes unlawful,” he said. “And that’s what we’re doing.”

The National Right to Life Committee’s model legislation, which advocates prohibiting abortion except to prevent the death of the pregnant person, recommends that states permit civil actions against people or entities that violate abortion laws “to prevent future violations.” It also suggests that people who have had or have sought to have an illegal abortion, as well as the expectant father and the parents of a pregnant minor, be allowed to pursue wrongful death actions.

Under the legislation, an action for wrongful death of an “unborn child” would be treated like that of a child who died after being born.

In one regard, Arizona has already implemented a piece of this model legislation as the state’s lawmakers have chipped away at access to abortion and enacted a myriad of regulations on doctors who provide the procedure.

The state’s “informed consent” statute for abortion, first signed into law by then-Gov. Jan Brewer in 2009, mandated an in-person counseling session and a 24-hour waiting period before an abortion. It allows a pregnant person, their husband or a maternal grandparent of a minor to sue if a physician does not properly obtain the pregnant person’s informed consent, and to receive damages for psychological, emotional and physical injuries, statutory damages and attorney fees.

The informed consent laws, which have changed over time, mandate that the patient be told about the “probable anatomical and physiological characteristics” of the embryo or fetus and the “immediate and long-term medical risks” associated with abortion, as well as alternatives to the procedure. Some abortion-rights groups and medical professionals have criticized informed consent processes, arguing the materials can be misleading and personify the embryo or fetus. A 2018 review of numerous studies concluded that having an abortion does not increase a person’s risk of infertility in their next pregnancy, nor is it linked to a higher risk of breast cancer or preterm birth, among other issues.

The wrongful death suit comes at a time of extraordinary confusion over abortion law in Arizona.

Until Roe v. Wade was handed down in 1973, establishing a constitutional right to abortion, a law dating to before statehood had banned the procedure. In March, Gov. Doug Ducey, a Republican who has called Arizona “the most pro-life state in the country,” signed into law a bill outlawing abortions after 15 weeks, and said that law would supersede the pre-statehood ban if Roe were overturned. But now that Roe has been overturned, Arizona Attorney General Mark Brnovich, another Republican, said he intends to enforce the pre-statehood ban, which outlawed abortion except to preserve the life of the person seeking the procedure. On July 14, he filed a motion to lift an injunction on the law, which would make it enforceable.

Adding to the muddle, a U.S. district court judge on July 11 blocked part of a 2021 Arizona law that would classify fertilized eggs, embryos and fetuses as people starting at conception, ruling that the attorney general cannot use the so-called personhood law against abortion providers. Following the Supreme Court decision in Dobbs, eight of the state’s nine abortion providers – all located in three Arizona counties – halted abortion services, but following the emergency injunction some are again offering them.

In the wrongful death claim, Mr. Martineau argued that the woman’s consent was invalidated because the doctors didn’t follow the informed consent statute. Although the woman signed four consent documents, the suit claims that “evidence shows that in her rush to maximize profits,” the clinic’s owner, Dr. Gabrielle Goodrick, “cut corners.” Mr. Martineau alleged that Dr. Goodrick and another doctor didn’t inform the woman of the loss of “maternal-fetal” attachment, about the alternatives to abortion or that if not for the abortion, the embryo would likely have been “delivered to term,” among other violations.

Tom Slutes, Dr. Goodrick’s lawyer, called the lawsuit “ridiculous.”

“They didn’t cut any corners,” he said, adding that the woman “clearly knew what was going to happen and definitely, strongly” wanted the abortion. Regardless of the information the woman received, she wouldn’t have changed her mind, Mr. Slutes said. Mr. Slutes referenced the deposition, where the woman said she “felt completely informed.”

Mr. Martineau said in an interview that Mr. Villegas isn’t motivated by collecting money from the lawsuit.

“He has no desire to harass” his ex-wife, Mr. Martineau said. “All he wants to do is make sure it doesn’t happen to another father.”

In a deposition, Mr. Villegas’ ex-wife said that he was emotionally abusive during their marriage, which lasted nearly 5 years. At first, she said, Mr. Villegas seemed like the “greatest guy I’ve ever met in my life,” taking her to California for a week as a birthday gift. But as the marriage progressed, she said, there were times he wouldn’t allow her to get a job or leave the house unless she was with him.

The woman alleged that Mr. Villegas made fake social media profiles, hacked into her social media accounts and threatened to “blackmail” her if she left him during his failed campaign to be a justice of the peace in Gila County, outside of Phoenix.

Mr. Villegas denied the allegations about his relationship but declined to comment further for this story, Mr. Martineau said.

Carliss Chatman, an associate law professor at Washington and Lee University in Virginia, said certain civil remedies can also be a mechanism for men to continue to abuse their former partners through the court system.

“What happens if the father who is suing on behalf of the fetus is your rapist or your abuser? It’s another way to torture a woman,” Ms. Chatman said.

Ms. Chatman added that these legal actions can be a deterrent for physicians in states where abortion is banned after a certain gestational period, because the threat of civil suits makes it harder for doctors to get insurance.

The lawsuit has added to the stresses on Dr. Goodrick, who has been performing abortions in Arizona since the mid-1990s, and her practice. She said that, since the lawsuit was filed, the annual cost of her medical malpractice insurance has risen from $32,000 to $67,000.

Before providers in Arizona halted abortions following the Supreme Court decision, people would begin lining up outside Dr. Goodrick’s clinic at 6 a.m., sometimes with lawn chairs in hand, like “a concert line,” Dr. Goodrick said.

“Every year there’s something and we never know what it’s going to be,” Dr. Goodrick said recently at her Phoenix clinic. “I’m kind of desensitized to it all.”



Nicole Santa Cruz is a reporter covering issues of inequality in the Southwest.

This story was originally published on ProPublica. ProPublica is a nonprofit newsroom that investigates abuses of power. Sign up to receive their biggest stories as soon as they’re published.

Nearly 4 years after a woman ended an unwanted pregnancy with abortion pills obtained at a Phoenix clinic, she finds herself mired in an ongoing lawsuit over that decision.

A judge allowed the woman’s ex-husband to establish an estate for the embryo, which had been aborted in its seventh week of development. The ex-husband filed a wrongful death lawsuit against the clinic and its doctors in 2020, alleging that physicians failed to obtain proper informed consent from the woman as required by Arizona law.

Across the United States, people have sued for negligence in the death of a fetus or embryo in cases where a pregnant person has been killed in a car crash or a pregnancy was lost because of alleged wrongdoing by a physician. But a court action claiming the wrongful death of an aborted embryo or fetus is a more novel strategy, legal experts said.

The experts said this rare tactic could become more common, as anti-abortion groups have signaled their desire to further limit reproductive rights following the U.S. Supreme Court’s decision in Dobbs v. Jackson Women’s Health Organization, which overturned Roe v. Wade. The Arizona lawsuit and others that may follow could also be an attempt to discourage and intimidate providers and harass plaintiffs’ former romantic partners, experts said.

Lucinda Finley, a law professor at the University at Buffalo who specializes in tort law and reproductive rights, said the Arizona case is a “harbinger of things to come” and called it “troubling for the future.”

Ms. Finley said she expects state lawmakers and anti-abortion groups to use “unprecedented strategies” to try to prevent people from traveling to obtain abortions or block them from obtaining information on where to seek one.

Perhaps the most extreme example is in Texas, where the Texas Heartbeat Act, signed into law in May 2021 and upheld by the U.S. Supreme Court in December, allows private citizens to sue a person who performs or aids in an abortion.

“It’s much bigger than these wrongful death suits,” Ms. Finley said.

Civia Tamarkin, president of the National Council of Jewish Women Arizona, which advocates for reproductive rights, said the Arizona lawsuit is part of a larger agenda that anti-abortion advocates are working toward.

“It’s a lawsuit that appears to be a trial balloon to see how far the attorney and the plaintiff can push the limits of the law, the limits of reason, the limits of science and medicine,” Ms. Tamarkin said.

In July 2018, the ex-husband, Mario Villegas, accompanied his then-wife to three medical appointments – a consultation, the abortion, and a follow-up. The woman, who ProPublica is not identifying for privacy reasons, said in a deposition in the wrongful death suit that at the time of the procedure the two were already talking about obtaining a divorce, which was finalized later that year.

“We were not happy together at all,” she said.

Mr. Villegas, a former Marine from Globe, Ariz., a mining town east of Phoenix, had been married twice before and has other children. He has since moved out of state.

In a form his then-wife filled out at the clinic, she said she was seeking an abortion because she was not ready to be a parent and her relationship with Mr. Villegas was unstable, according to court records. She also checked a box affirming that “I am comfortable with my decision to terminate this pregnancy.” The woman declined to speak on the record with ProPublica out of fear for her safety.

The following year, in 2019, Mr. Villegas learned about an Alabama man who hadn’t wanted his ex-girlfriend to have an abortion and sued the Alabama Women’s Center for Reproductive Alternatives in Huntsville on behalf of an embryo that was aborted at six weeks.

To sue on behalf of the embryo, the would-be father, Ryan Magers, went to probate court where he asked a judge to appoint him as the personal representative of the estate. In probate court, a judge may appoint someone to represent the estate of a person who has died without a will. That representative then has the authority to distribute the estate’s assets to beneficiaries.

When Mr. Magers filed to open an estate for the embryo, his attorney cited various Alabama court rulings involving pregnant people and a 2018 amendment to the Alabama Constitution recognizing the “sanctity of unborn life and the rights of unborn children.”

A probate judge appointed Mr. Magers representative of the estate, giving him legal standing to sue for damages in the wrongful death claim. The case, believed to be the first instance in which an aborted embryo was given legal rights, made national headlines.

It’s unclear how many states allow an estate to be opened on behalf of an embryo or fetus. Some states, like Arizona, don’t explicitly define what counts as a deceased person in their probate code, leaving it to a judge to decide. In a handful of states, laws define embryos and fetuses as a person at conception, which could allow for an estate, but it’s rare.

An Alabama circuit court judge eventually dismissed Mr. Magers’ wrongful death lawsuit, stating that the claims were “precluded by State and Federal laws.”

Mr. Villegas contacted Mr. Magers’ attorney, Brent Helms, about pursuing a similar action in Arizona and was referred to J. Stanley Martineau, an Arizona attorney who had flown to Alabama to talk to Mr. Helms about Mr. Magers’ case.

In August 2020, Mr. Villegas filed a petition to be appointed personal representative of the estate of “Baby Villegas.” His ex-wife opposed the action and contacted a legal advocacy organization focused on reproductive justice, which helped her obtain a lawyer.

In court filings, Mr. Villegas said he prefers to think of “Baby Villegas” as a girl, although the sex of the embryo was never determined, and his lawyer argued that there isn’t an Arizona case that explicitly defines a deceased person, “so the issue appears to be an open one in Arizona.”

In a 2021 motion arguing for dismissal, the ex-wife’s attorney, Louis Silverman, argued that Arizona’s probate code doesn’t authorize the appointment of a personal representative for an embryo, and that granting Mr. Villegas’ request would violate a woman’s constitutional right to decide whether to carry a pregnancy to term.

“U.S. Supreme Court precedent has long protected the constitutional right of a woman to obtain an abortion, including that the decision whether to do so belongs to the woman alone – even where her partner, spouse, or ex-spouse disagrees with that decision,” Mr. Silverman said last year.

Gila County Superior Court Judge Bryan B. Chambers said in an order denying the motion that his decision allows Mr. Villegas to make the argument that the embryo is a person in a wrongful death lawsuit, but that he has not reached that conclusion at this stage. Mr. Villegas was later appointed the personal representative of the estate.

As states determine what is legal in the wake of Dobbs and legislators propose new abortion laws, anti-abortion groups such as the National Right to Life Committee see civil suits as a way to enforce abortion bans and have released model legislation they hope sympathetic legislators will duplicate in statehouses nationwide.

“In addition to criminal penalties and medical license revocation, civil remedies will be critical to ensure that unborn lives are protected from illegal abortions,” the group wrote in a June 15 letter to its state affiliates that included the model legislation.

James Bopp Jr., general counsel for the committee, said in an interview with ProPublica that such actions will be necessary because some “radical Democrat” prosecutors have signaled they won’t enforce criminal abortion bans. Last month, 90 prosecutors from across the country indicated that they would not prosecute those who seek abortions.

“The civil remedies follow what the criminal law makes unlawful,” he said. “And that’s what we’re doing.”

The National Right to Life Committee’s model legislation, which advocates prohibiting abortion except to prevent the death of the pregnant person, recommends that states permit civil actions against people or entities that violate abortion laws “to prevent future violations.” It also suggests that people who have had or have sought to have an illegal abortion, as well as the expectant father and the parents of a pregnant minor, be allowed to pursue wrongful death actions.

Under the legislation, an action for wrongful death of an “unborn child” would be treated like that of a child who died after being born.

In one regard, Arizona has already implemented a piece of this model legislation as the state’s lawmakers have chipped away at access to abortion and enacted a myriad of regulations on doctors who provide the procedure.

The state’s “informed consent” statute for abortion, first signed into law by then-Gov. Jan Brewer in 2009, mandated an in-person counseling session and a 24-hour waiting period before an abortion. It allows a pregnant person, their husband or a maternal grandparent of a minor to sue if a physician does not properly obtain the pregnant person’s informed consent, and to receive damages for psychological, emotional and physical injuries, statutory damages and attorney fees.

The informed consent laws, which have changed over time, mandate that the patient be told about the “probable anatomical and physiological characteristics” of the embryo or fetus and the “immediate and long-term medical risks” associated with abortion, as well as alternatives to the procedure. Some abortion-rights groups and medical professionals have criticized informed consent processes, arguing the materials can be misleading and personify the embryo or fetus. A 2018 review of numerous studies concluded that having an abortion does not increase a person’s risk of infertility in their next pregnancy, nor is it linked to a higher risk of breast cancer or preterm birth, among other issues.

The wrongful death suit comes at a time of extraordinary confusion over abortion law in Arizona.

Until Roe v. Wade was handed down in 1973, establishing a constitutional right to abortion, a law dating to before statehood had banned the procedure. In March, Gov. Doug Ducey, a Republican who has called Arizona “the most pro-life state in the country,” signed into law a bill outlawing abortions after 15 weeks, and said that law would supersede the pre-statehood ban if Roe were overturned. But now that Roe has been overturned, Arizona Attorney General Mark Brnovich, another Republican, said he intends to enforce the pre-statehood ban, which outlawed abortion except to preserve the life of the person seeking the procedure. On July 14, he filed a motion to lift an injunction on the law, which would make it enforceable.

Adding to the muddle, a U.S. district court judge on July 11 blocked part of a 2021 Arizona law that would classify fertilized eggs, embryos and fetuses as people starting at conception, ruling that the attorney general cannot use the so-called personhood law against abortion providers. Following the Supreme Court decision in Dobbs, eight of the state’s nine abortion providers – all located in three Arizona counties – halted abortion services, but following the emergency injunction some are again offering them.

In the wrongful death claim, Mr. Martineau argued that the woman’s consent was invalidated because the doctors didn’t follow the informed consent statute. Although the woman signed four consent documents, the suit claims that “evidence shows that in her rush to maximize profits,” the clinic’s owner, Dr. Gabrielle Goodrick, “cut corners.” Mr. Martineau alleged that Dr. Goodrick and another doctor didn’t inform the woman of the loss of “maternal-fetal” attachment, about the alternatives to abortion or that if not for the abortion, the embryo would likely have been “delivered to term,” among other violations.

Tom Slutes, Dr. Goodrick’s lawyer, called the lawsuit “ridiculous.”

“They didn’t cut any corners,” he said, adding that the woman “clearly knew what was going to happen and definitely, strongly” wanted the abortion. Regardless of the information the woman received, she wouldn’t have changed her mind, Mr. Slutes said. Mr. Slutes referenced the deposition, where the woman said she “felt completely informed.”

Mr. Martineau said in an interview that Mr. Villegas isn’t motivated by collecting money from the lawsuit.

“He has no desire to harass” his ex-wife, Mr. Martineau said. “All he wants to do is make sure it doesn’t happen to another father.”

In a deposition, Mr. Villegas’ ex-wife said that he was emotionally abusive during their marriage, which lasted nearly 5 years. At first, she said, Mr. Villegas seemed like the “greatest guy I’ve ever met in my life,” taking her to California for a week as a birthday gift. But as the marriage progressed, she said, there were times he wouldn’t allow her to get a job or leave the house unless she was with him.

The woman alleged that Mr. Villegas made fake social media profiles, hacked into her social media accounts and threatened to “blackmail” her if she left him during his failed campaign to be a justice of the peace in Gila County, outside of Phoenix.

Mr. Villegas denied the allegations about his relationship but declined to comment further for this story, Mr. Martineau said.

Carliss Chatman, an associate law professor at Washington and Lee University in Virginia, said certain civil remedies can also be a mechanism for men to continue to abuse their former partners through the court system.

“What happens if the father who is suing on behalf of the fetus is your rapist or your abuser? It’s another way to torture a woman,” Ms. Chatman said.

Ms. Chatman added that these legal actions can be a deterrent for physicians in states where abortion is banned after a certain gestational period, because the threat of civil suits makes it harder for doctors to get insurance.

The lawsuit has added to the stresses on Dr. Goodrick, who has been performing abortions in Arizona since the mid-1990s, and her practice. She said that, since the lawsuit was filed, the annual cost of her medical malpractice insurance has risen from $32,000 to $67,000.

Before providers in Arizona halted abortions following the Supreme Court decision, people would begin lining up outside Dr. Goodrick’s clinic at 6 a.m., sometimes with lawn chairs in hand, like “a concert line,” Dr. Goodrick said.

“Every year there’s something and we never know what it’s going to be,” Dr. Goodrick said recently at her Phoenix clinic. “I’m kind of desensitized to it all.”



Nicole Santa Cruz is a reporter covering issues of inequality in the Southwest.

This story was originally published on ProPublica. ProPublica is a nonprofit newsroom that investigates abuses of power. Sign up to receive their biggest stories as soon as they’re published.

Nearly 4 years after a woman ended an unwanted pregnancy with abortion pills obtained at a Phoenix clinic, she finds herself mired in an ongoing lawsuit over that decision.

A judge allowed the woman’s ex-husband to establish an estate for the embryo, which had been aborted in its seventh week of development. The ex-husband filed a wrongful death lawsuit against the clinic and its doctors in 2020, alleging that physicians failed to obtain proper informed consent from the woman as required by Arizona law.

Across the United States, people have sued for negligence in the death of a fetus or embryo in cases where a pregnant person has been killed in a car crash or a pregnancy was lost because of alleged wrongdoing by a physician. But a court action claiming the wrongful death of an aborted embryo or fetus is a more novel strategy, legal experts said.

The experts said this rare tactic could become more common, as anti-abortion groups have signaled their desire to further limit reproductive rights following the U.S. Supreme Court’s decision in Dobbs v. Jackson Women’s Health Organization, which overturned Roe v. Wade. The Arizona lawsuit and others that may follow could also be an attempt to discourage and intimidate providers and harass plaintiffs’ former romantic partners, experts said.

Lucinda Finley, a law professor at the University at Buffalo who specializes in tort law and reproductive rights, said the Arizona case is a “harbinger of things to come” and called it “troubling for the future.”

Ms. Finley said she expects state lawmakers and anti-abortion groups to use “unprecedented strategies” to try to prevent people from traveling to obtain abortions or block them from obtaining information on where to seek one.

Perhaps the most extreme example is in Texas, where the Texas Heartbeat Act, signed into law in May 2021 and upheld by the U.S. Supreme Court in December, allows private citizens to sue a person who performs or aids in an abortion.

“It’s much bigger than these wrongful death suits,” Ms. Finley said.

Civia Tamarkin, president of the National Council of Jewish Women Arizona, which advocates for reproductive rights, said the Arizona lawsuit is part of a larger agenda that anti-abortion advocates are working toward.

“It’s a lawsuit that appears to be a trial balloon to see how far the attorney and the plaintiff can push the limits of the law, the limits of reason, the limits of science and medicine,” Ms. Tamarkin said.

In July 2018, the ex-husband, Mario Villegas, accompanied his then-wife to three medical appointments – a consultation, the abortion, and a follow-up. The woman, who ProPublica is not identifying for privacy reasons, said in a deposition in the wrongful death suit that at the time of the procedure the two were already talking about obtaining a divorce, which was finalized later that year.

“We were not happy together at all,” she said.

Mr. Villegas, a former Marine from Globe, Ariz., a mining town east of Phoenix, had been married twice before and has other children. He has since moved out of state.

In a form his then-wife filled out at the clinic, she said she was seeking an abortion because she was not ready to be a parent and her relationship with Mr. Villegas was unstable, according to court records. She also checked a box affirming that “I am comfortable with my decision to terminate this pregnancy.” The woman declined to speak on the record with ProPublica out of fear for her safety.

The following year, in 2019, Mr. Villegas learned about an Alabama man who hadn’t wanted his ex-girlfriend to have an abortion and sued the Alabama Women’s Center for Reproductive Alternatives in Huntsville on behalf of an embryo that was aborted at six weeks.

To sue on behalf of the embryo, the would-be father, Ryan Magers, went to probate court where he asked a judge to appoint him as the personal representative of the estate. In probate court, a judge may appoint someone to represent the estate of a person who has died without a will. That representative then has the authority to distribute the estate’s assets to beneficiaries.

When Mr. Magers filed to open an estate for the embryo, his attorney cited various Alabama court rulings involving pregnant people and a 2018 amendment to the Alabama Constitution recognizing the “sanctity of unborn life and the rights of unborn children.”

A probate judge appointed Mr. Magers representative of the estate, giving him legal standing to sue for damages in the wrongful death claim. The case, believed to be the first instance in which an aborted embryo was given legal rights, made national headlines.

It’s unclear how many states allow an estate to be opened on behalf of an embryo or fetus. Some states, like Arizona, don’t explicitly define what counts as a deceased person in their probate code, leaving it to a judge to decide. In a handful of states, laws define embryos and fetuses as a person at conception, which could allow for an estate, but it’s rare.

An Alabama circuit court judge eventually dismissed Mr. Magers’ wrongful death lawsuit, stating that the claims were “precluded by State and Federal laws.”

Mr. Villegas contacted Mr. Magers’ attorney, Brent Helms, about pursuing a similar action in Arizona and was referred to J. Stanley Martineau, an Arizona attorney who had flown to Alabama to talk to Mr. Helms about Mr. Magers’ case.

In August 2020, Mr. Villegas filed a petition to be appointed personal representative of the estate of “Baby Villegas.” His ex-wife opposed the action and contacted a legal advocacy organization focused on reproductive justice, which helped her obtain a lawyer.

In court filings, Mr. Villegas said he prefers to think of “Baby Villegas” as a girl, although the sex of the embryo was never determined, and his lawyer argued that there isn’t an Arizona case that explicitly defines a deceased person, “so the issue appears to be an open one in Arizona.”

In a 2021 motion arguing for dismissal, the ex-wife’s attorney, Louis Silverman, argued that Arizona’s probate code doesn’t authorize the appointment of a personal representative for an embryo, and that granting Mr. Villegas’ request would violate a woman’s constitutional right to decide whether to carry a pregnancy to term.

“U.S. Supreme Court precedent has long protected the constitutional right of a woman to obtain an abortion, including that the decision whether to do so belongs to the woman alone – even where her partner, spouse, or ex-spouse disagrees with that decision,” Mr. Silverman said last year.

Gila County Superior Court Judge Bryan B. Chambers said in an order denying the motion that his decision allows Mr. Villegas to make the argument that the embryo is a person in a wrongful death lawsuit, but that he has not reached that conclusion at this stage. Mr. Villegas was later appointed the personal representative of the estate.

As states determine what is legal in the wake of Dobbs and legislators propose new abortion laws, anti-abortion groups such as the National Right to Life Committee see civil suits as a way to enforce abortion bans and have released model legislation they hope sympathetic legislators will duplicate in statehouses nationwide.

“In addition to criminal penalties and medical license revocation, civil remedies will be critical to ensure that unborn lives are protected from illegal abortions,” the group wrote in a June 15 letter to its state affiliates that included the model legislation.

James Bopp Jr., general counsel for the committee, said in an interview with ProPublica that such actions will be necessary because some “radical Democrat” prosecutors have signaled they won’t enforce criminal abortion bans. Last month, 90 prosecutors from across the country indicated that they would not prosecute those who seek abortions.

“The civil remedies follow what the criminal law makes unlawful,” he said. “And that’s what we’re doing.”

The National Right to Life Committee’s model legislation, which advocates prohibiting abortion except to prevent the death of the pregnant person, recommends that states permit civil actions against people or entities that violate abortion laws “to prevent future violations.” It also suggests that people who have had or have sought to have an illegal abortion, as well as the expectant father and the parents of a pregnant minor, be allowed to pursue wrongful death actions.

Under the legislation, an action for wrongful death of an “unborn child” would be treated like that of a child who died after being born.

In one regard, Arizona has already implemented a piece of this model legislation as the state’s lawmakers have chipped away at access to abortion and enacted a myriad of regulations on doctors who provide the procedure.

The state’s “informed consent” statute for abortion, first signed into law by then-Gov. Jan Brewer in 2009, mandated an in-person counseling session and a 24-hour waiting period before an abortion. It allows a pregnant person, their husband or a maternal grandparent of a minor to sue if a physician does not properly obtain the pregnant person’s informed consent, and to receive damages for psychological, emotional and physical injuries, statutory damages and attorney fees.

The informed consent laws, which have changed over time, mandate that the patient be told about the “probable anatomical and physiological characteristics” of the embryo or fetus and the “immediate and long-term medical risks” associated with abortion, as well as alternatives to the procedure. Some abortion-rights groups and medical professionals have criticized informed consent processes, arguing the materials can be misleading and personify the embryo or fetus. A 2018 review of numerous studies concluded that having an abortion does not increase a person’s risk of infertility in their next pregnancy, nor is it linked to a higher risk of breast cancer or preterm birth, among other issues.

The wrongful death suit comes at a time of extraordinary confusion over abortion law in Arizona.

Until Roe v. Wade was handed down in 1973, establishing a constitutional right to abortion, a law dating to before statehood had banned the procedure. In March, Gov. Doug Ducey, a Republican who has called Arizona “the most pro-life state in the country,” signed into law a bill outlawing abortions after 15 weeks, and said that law would supersede the pre-statehood ban if Roe were overturned. But now that Roe has been overturned, Arizona Attorney General Mark Brnovich, another Republican, said he intends to enforce the pre-statehood ban, which outlawed abortion except to preserve the life of the person seeking the procedure. On July 14, he filed a motion to lift an injunction on the law, which would make it enforceable.

Adding to the muddle, a U.S. district court judge on July 11 blocked part of a 2021 Arizona law that would classify fertilized eggs, embryos and fetuses as people starting at conception, ruling that the attorney general cannot use the so-called personhood law against abortion providers. Following the Supreme Court decision in Dobbs, eight of the state’s nine abortion providers – all located in three Arizona counties – halted abortion services, but following the emergency injunction some are again offering them.

In the wrongful death claim, Mr. Martineau argued that the woman’s consent was invalidated because the doctors didn’t follow the informed consent statute. Although the woman signed four consent documents, the suit claims that “evidence shows that in her rush to maximize profits,” the clinic’s owner, Dr. Gabrielle Goodrick, “cut corners.” Mr. Martineau alleged that Dr. Goodrick and another doctor didn’t inform the woman of the loss of “maternal-fetal” attachment, about the alternatives to abortion or that if not for the abortion, the embryo would likely have been “delivered to term,” among other violations.

Tom Slutes, Dr. Goodrick’s lawyer, called the lawsuit “ridiculous.”

“They didn’t cut any corners,” he said, adding that the woman “clearly knew what was going to happen and definitely, strongly” wanted the abortion. Regardless of the information the woman received, she wouldn’t have changed her mind, Mr. Slutes said. Mr. Slutes referenced the deposition, where the woman said she “felt completely informed.”

Mr. Martineau said in an interview that Mr. Villegas isn’t motivated by collecting money from the lawsuit.

“He has no desire to harass” his ex-wife, Mr. Martineau said. “All he wants to do is make sure it doesn’t happen to another father.”

In a deposition, Mr. Villegas’ ex-wife said that he was emotionally abusive during their marriage, which lasted nearly 5 years. At first, she said, Mr. Villegas seemed like the “greatest guy I’ve ever met in my life,” taking her to California for a week as a birthday gift. But as the marriage progressed, she said, there were times he wouldn’t allow her to get a job or leave the house unless she was with him.

The woman alleged that Mr. Villegas made fake social media profiles, hacked into her social media accounts and threatened to “blackmail” her if she left him during his failed campaign to be a justice of the peace in Gila County, outside of Phoenix.

Mr. Villegas denied the allegations about his relationship but declined to comment further for this story, Mr. Martineau said.

Carliss Chatman, an associate law professor at Washington and Lee University in Virginia, said certain civil remedies can also be a mechanism for men to continue to abuse their former partners through the court system.

“What happens if the father who is suing on behalf of the fetus is your rapist or your abuser? It’s another way to torture a woman,” Ms. Chatman said.

Ms. Chatman added that these legal actions can be a deterrent for physicians in states where abortion is banned after a certain gestational period, because the threat of civil suits makes it harder for doctors to get insurance.

The lawsuit has added to the stresses on Dr. Goodrick, who has been performing abortions in Arizona since the mid-1990s, and her practice. She said that, since the lawsuit was filed, the annual cost of her medical malpractice insurance has risen from $32,000 to $67,000.

Before providers in Arizona halted abortions following the Supreme Court decision, people would begin lining up outside Dr. Goodrick’s clinic at 6 a.m., sometimes with lawn chairs in hand, like “a concert line,” Dr. Goodrick said.

“Every year there’s something and we never know what it’s going to be,” Dr. Goodrick said recently at her Phoenix clinic. “I’m kind of desensitized to it all.”



Nicole Santa Cruz is a reporter covering issues of inequality in the Southwest.

This story was originally published on ProPublica. ProPublica is a nonprofit newsroom that investigates abuses of power. Sign up to receive their biggest stories as soon as they’re published.

MUSCATINE, IOWA – Bailee Tordai, who was 33 weeks into her pregnancy, barely made it to the prenatal checkup. Her clunky old Jeep couldn’t complete the 2-mile trip from her house to the University of Iowa’s outreach clinic in her southeastern Iowa hometown. It was a hot June day, and a wiring problem made the Jeep conk out in the street.

A passerby helped Ms.Tordai, 22, push her stricken vehicle off the road and into a parking lot. Then she called her stepdad for a ride to the clinic.

Jaclyn Roman, a nurse-midwife, walked into the exam room. “I heard your car broke down.”

“Yup. You want to buy it? Five bucks!” Ms. Tordai joked.

Her lack of reliable transportation won’t be a laughing matter in August, when her baby is due. She will need to arrange for someone to drive her about 40 miles northwest to the University of Iowa Hospitals and Clinics in Iowa City. She can’t give birth at Muscatine’s hospital because it shuttered its birthing unit in 2020.

Ms. Roman is part of an unusual effort to minimize the harm caused by such closures. She’s one of 11 certified nurse-midwives from the University of Iowa who travel regularly to Muscatine and Washington, another southeastern Iowa town where the local hospital closed its birthing unit. The university’s pilot project, which is supported by a federal grant, doesn’t aim to reopen shuttered birthing units. Instead, the midwife team helps ensure area women receive related services. Last year, it served more than 500 patients in Muscatine and Washington.

Muscatine is one of hundreds of rural areas in the United States where hospitals have dropped birthing services during the past 2 decades, often because they lack obstetricians and other specialized staff members.

Hospital industry leaders say birthing units also tend to lose money, largely because of low payments from Medicaid, the public health insurance program that covers more than 40% of births in the United States and an even greater share in many rural areas.

The loss of labor-and-delivery services hits especially hard for women who lack resources and time to travel for care.

Muscatine, which is on the Mississippi River, has more than 23,000 residents, making it a relatively large town by Iowa standards. But its hospital is one of 41 Iowa facilities that have closed their birthing units since 2000, according to the Iowa Department of Public Health. Most were in rural areas. Just one has reopened, and only 56 Iowa hospitals now have birthing units.

The nurse-midwife team’s work includes crucial prenatal checkups. Most pregnant people are supposed to have a dozen or more such appointments before giving birth. Health care providers use the checkups to track how a pregnancy is progressing and to watch for signs of high blood pressure and other problems that can lead to premature births, stillbirths, or even maternal deaths. The midwives also advise women on how to keep themselves and their babies healthy after birth.

Karen Jefferson, DM, director of midwifery practice for the American College of Nurse-Midwives, said the University of Iowa team’s approach is an innovative way to address needs in rural areas that have lost hospital birthing units. “How wonderful would it be to see a provider in your town, instead of driving 40 miles for your prenatal visits – especially toward the end of pregnancy, when you’re going every week,” said Dr. Jefferson, who lives in rural New York.

Midwives can provide many other types of care for women and for babies. In theory, they could even open rural birthing centers outside of hospitals, Dr. Jefferson said. But they would need to overcome concerns about financing and about the availability of surgeons to do emergency cesarean sections, which she said are rarely needed in low-risk births.

The University of Iowa midwives focus on low-risk pregnancies, referring patients with significant health issues to physician specialists in Iowa City. Often, those specialists can visit with the patients and the midwives via video conference in the small-town clinics.

The loss of a hospital obstetrics unit can make finding local maternity care harder for rural families.

Ms. Tordai can attest that if patients must travel far for prenatal appointments, they’re less likely to get to them all. If she had to go to Iowa City for each of hers, repeatedly taking 3 hours off from her job managing a pizza restaurant would be tough, she said. On that June day her Jeep broke down, she would have canceled her appointment.

Instead, she wound up on an exam table at the Muscatine clinic listening to her baby’s heartbeat on a monitor and watching as Ms. Roman measured her belly.

“Nice job being perfect,” the midwife told her during the checkup.

Ms. Roman asked Ms. Tordai to describe her baby’s movements. “Constant,” she replied with a smile.

Ms. Roman asked whether she planned to breastfeed. Ms. Tordai said she didn’t have much luck with her first daughter, Aspen, now 4.

“Have you thought about a breastfeeding class?” the midwife asked.

“I don’t have time for that,” Ms. Tordai replied. Ms. Roman continued to coax her, noting where a breastfeeding class is available online.

Near the end of the appointment, Ms. Tordai asked Ms. Roman whether she could schedule an induced birth at the University of Iowa hospital. The midwife told her that, in general, letting labor begin on its own is better than artificially starting it.

But there was the matter of unreliable transportation. Ms. Tordai explained that scheduling the birth would help her arrange to have her mother drive her to the hospital in Iowa City. Ms. Roman agreed that transportation is a legitimate reason and arranged for an induced labor on Aug. 10.

The University of Iowa midwife team started offering services in 2020 in a clinic about 2 miles from Trinity Muscatine hospital. The hospital is owned by UnityPoint Health, a large nonprofit hospital system that blamed a lack of available obstetricians for the closure of the Muscatine birthing unit. At the time, UnityPoint leaders said they hoped to reopen the unit if they could recruit new obstetricians to the area.

Kristy Phillipson, a UnityPoint Health spokesperson, told KHN in June that the company has continued to try to recruit physicians, including for the Muscatine hospital. Although it has not reopened the birthing unit, the company regularly sends an obstetrician and other staff members to provide prenatal care and related services, she said.

Most pregnant patients from the area who choose UnityPoint for their care wind up giving birth at the system’s hospital in Bettendorf, a 45-minute drive to the east.

The University of Iowa midwife team has no plans to open its own birthing centers, but it hopes to expand its rural clinic service to other underserved towns. To do so, the university would need to hire more nurse-midwives, which could be a challenge. According to the Iowa Board of Nursing, 120 licensed nurse-midwives live in the state of 3 million people.

The University of Iowa plans to address that by starting the state’s first nurse-midwife training program in 2023. The master’s degree program, which will emphasize rural service, will train registered nurses to become nurse-midwives. It eventually could graduate eight people per year, said Amber Goodrich, a University of Iowa midwife helping lead the effort.

Those graduates could fill gaps throughout rural areas, where even more hospitals may shutter their birthing units in the coming years.

“This crisis is going nowhere fast,” Ms. Goodrich said.

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

MUSCATINE, IOWA – Bailee Tordai, who was 33 weeks into her pregnancy, barely made it to the prenatal checkup. Her clunky old Jeep couldn’t complete the 2-mile trip from her house to the University of Iowa’s outreach clinic in her southeastern Iowa hometown. It was a hot June day, and a wiring problem made the Jeep conk out in the street.

A passerby helped Ms.Tordai, 22, push her stricken vehicle off the road and into a parking lot. Then she called her stepdad for a ride to the clinic.

Jaclyn Roman, a nurse-midwife, walked into the exam room. “I heard your car broke down.”

“Yup. You want to buy it? Five bucks!” Ms. Tordai joked.

Her lack of reliable transportation won’t be a laughing matter in August, when her baby is due. She will need to arrange for someone to drive her about 40 miles northwest to the University of Iowa Hospitals and Clinics in Iowa City. She can’t give birth at Muscatine’s hospital because it shuttered its birthing unit in 2020.

Ms. Roman is part of an unusual effort to minimize the harm caused by such closures. She’s one of 11 certified nurse-midwives from the University of Iowa who travel regularly to Muscatine and Washington, another southeastern Iowa town where the local hospital closed its birthing unit. The university’s pilot project, which is supported by a federal grant, doesn’t aim to reopen shuttered birthing units. Instead, the midwife team helps ensure area women receive related services. Last year, it served more than 500 patients in Muscatine and Washington.

Muscatine is one of hundreds of rural areas in the United States where hospitals have dropped birthing services during the past 2 decades, often because they lack obstetricians and other specialized staff members.

Hospital industry leaders say birthing units also tend to lose money, largely because of low payments from Medicaid, the public health insurance program that covers more than 40% of births in the United States and an even greater share in many rural areas.

The loss of labor-and-delivery services hits especially hard for women who lack resources and time to travel for care.

Muscatine, which is on the Mississippi River, has more than 23,000 residents, making it a relatively large town by Iowa standards. But its hospital is one of 41 Iowa facilities that have closed their birthing units since 2000, according to the Iowa Department of Public Health. Most were in rural areas. Just one has reopened, and only 56 Iowa hospitals now have birthing units.

The nurse-midwife team’s work includes crucial prenatal checkups. Most pregnant people are supposed to have a dozen or more such appointments before giving birth. Health care providers use the checkups to track how a pregnancy is progressing and to watch for signs of high blood pressure and other problems that can lead to premature births, stillbirths, or even maternal deaths. The midwives also advise women on how to keep themselves and their babies healthy after birth.

Karen Jefferson, DM, director of midwifery practice for the American College of Nurse-Midwives, said the University of Iowa team’s approach is an innovative way to address needs in rural areas that have lost hospital birthing units. “How wonderful would it be to see a provider in your town, instead of driving 40 miles for your prenatal visits – especially toward the end of pregnancy, when you’re going every week,” said Dr. Jefferson, who lives in rural New York.

Midwives can provide many other types of care for women and for babies. In theory, they could even open rural birthing centers outside of hospitals, Dr. Jefferson said. But they would need to overcome concerns about financing and about the availability of surgeons to do emergency cesarean sections, which she said are rarely needed in low-risk births.

The University of Iowa midwives focus on low-risk pregnancies, referring patients with significant health issues to physician specialists in Iowa City. Often, those specialists can visit with the patients and the midwives via video conference in the small-town clinics.

The loss of a hospital obstetrics unit can make finding local maternity care harder for rural families.

Ms. Tordai can attest that if patients must travel far for prenatal appointments, they’re less likely to get to them all. If she had to go to Iowa City for each of hers, repeatedly taking 3 hours off from her job managing a pizza restaurant would be tough, she said. On that June day her Jeep broke down, she would have canceled her appointment.

Instead, she wound up on an exam table at the Muscatine clinic listening to her baby’s heartbeat on a monitor and watching as Ms. Roman measured her belly.

“Nice job being perfect,” the midwife told her during the checkup.

Ms. Roman asked Ms. Tordai to describe her baby’s movements. “Constant,” she replied with a smile.

Ms. Roman asked whether she planned to breastfeed. Ms. Tordai said she didn’t have much luck with her first daughter, Aspen, now 4.

“Have you thought about a breastfeeding class?” the midwife asked.

“I don’t have time for that,” Ms. Tordai replied. Ms. Roman continued to coax her, noting where a breastfeeding class is available online.

Near the end of the appointment, Ms. Tordai asked Ms. Roman whether she could schedule an induced birth at the University of Iowa hospital. The midwife told her that, in general, letting labor begin on its own is better than artificially starting it.

But there was the matter of unreliable transportation. Ms. Tordai explained that scheduling the birth would help her arrange to have her mother drive her to the hospital in Iowa City. Ms. Roman agreed that transportation is a legitimate reason and arranged for an induced labor on Aug. 10.

The University of Iowa midwife team started offering services in 2020 in a clinic about 2 miles from Trinity Muscatine hospital. The hospital is owned by UnityPoint Health, a large nonprofit hospital system that blamed a lack of available obstetricians for the closure of the Muscatine birthing unit. At the time, UnityPoint leaders said they hoped to reopen the unit if they could recruit new obstetricians to the area.

Kristy Phillipson, a UnityPoint Health spokesperson, told KHN in June that the company has continued to try to recruit physicians, including for the Muscatine hospital. Although it has not reopened the birthing unit, the company regularly sends an obstetrician and other staff members to provide prenatal care and related services, she said.

Most pregnant patients from the area who choose UnityPoint for their care wind up giving birth at the system’s hospital in Bettendorf, a 45-minute drive to the east.

The University of Iowa midwife team has no plans to open its own birthing centers, but it hopes to expand its rural clinic service to other underserved towns. To do so, the university would need to hire more nurse-midwives, which could be a challenge. According to the Iowa Board of Nursing, 120 licensed nurse-midwives live in the state of 3 million people.

The University of Iowa plans to address that by starting the state’s first nurse-midwife training program in 2023. The master’s degree program, which will emphasize rural service, will train registered nurses to become nurse-midwives. It eventually could graduate eight people per year, said Amber Goodrich, a University of Iowa midwife helping lead the effort.

Those graduates could fill gaps throughout rural areas, where even more hospitals may shutter their birthing units in the coming years.

“This crisis is going nowhere fast,” Ms. Goodrich said.

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

MUSCATINE, IOWA – Bailee Tordai, who was 33 weeks into her pregnancy, barely made it to the prenatal checkup. Her clunky old Jeep couldn’t complete the 2-mile trip from her house to the University of Iowa’s outreach clinic in her southeastern Iowa hometown. It was a hot June day, and a wiring problem made the Jeep conk out in the street.

A passerby helped Ms.Tordai, 22, push her stricken vehicle off the road and into a parking lot. Then she called her stepdad for a ride to the clinic.

Jaclyn Roman, a nurse-midwife, walked into the exam room. “I heard your car broke down.”

“Yup. You want to buy it? Five bucks!” Ms. Tordai joked.

Her lack of reliable transportation won’t be a laughing matter in August, when her baby is due. She will need to arrange for someone to drive her about 40 miles northwest to the University of Iowa Hospitals and Clinics in Iowa City. She can’t give birth at Muscatine’s hospital because it shuttered its birthing unit in 2020.

Ms. Roman is part of an unusual effort to minimize the harm caused by such closures. She’s one of 11 certified nurse-midwives from the University of Iowa who travel regularly to Muscatine and Washington, another southeastern Iowa town where the local hospital closed its birthing unit. The university’s pilot project, which is supported by a federal grant, doesn’t aim to reopen shuttered birthing units. Instead, the midwife team helps ensure area women receive related services. Last year, it served more than 500 patients in Muscatine and Washington.

Muscatine is one of hundreds of rural areas in the United States where hospitals have dropped birthing services during the past 2 decades, often because they lack obstetricians and other specialized staff members.

Hospital industry leaders say birthing units also tend to lose money, largely because of low payments from Medicaid, the public health insurance program that covers more than 40% of births in the United States and an even greater share in many rural areas.

The loss of labor-and-delivery services hits especially hard for women who lack resources and time to travel for care.

Muscatine, which is on the Mississippi River, has more than 23,000 residents, making it a relatively large town by Iowa standards. But its hospital is one of 41 Iowa facilities that have closed their birthing units since 2000, according to the Iowa Department of Public Health. Most were in rural areas. Just one has reopened, and only 56 Iowa hospitals now have birthing units.

The nurse-midwife team’s work includes crucial prenatal checkups. Most pregnant people are supposed to have a dozen or more such appointments before giving birth. Health care providers use the checkups to track how a pregnancy is progressing and to watch for signs of high blood pressure and other problems that can lead to premature births, stillbirths, or even maternal deaths. The midwives also advise women on how to keep themselves and their babies healthy after birth.

Karen Jefferson, DM, director of midwifery practice for the American College of Nurse-Midwives, said the University of Iowa team’s approach is an innovative way to address needs in rural areas that have lost hospital birthing units. “How wonderful would it be to see a provider in your town, instead of driving 40 miles for your prenatal visits – especially toward the end of pregnancy, when you’re going every week,” said Dr. Jefferson, who lives in rural New York.

Midwives can provide many other types of care for women and for babies. In theory, they could even open rural birthing centers outside of hospitals, Dr. Jefferson said. But they would need to overcome concerns about financing and about the availability of surgeons to do emergency cesarean sections, which she said are rarely needed in low-risk births.

The University of Iowa midwives focus on low-risk pregnancies, referring patients with significant health issues to physician specialists in Iowa City. Often, those specialists can visit with the patients and the midwives via video conference in the small-town clinics.

The loss of a hospital obstetrics unit can make finding local maternity care harder for rural families.

Ms. Tordai can attest that if patients must travel far for prenatal appointments, they’re less likely to get to them all. If she had to go to Iowa City for each of hers, repeatedly taking 3 hours off from her job managing a pizza restaurant would be tough, she said. On that June day her Jeep broke down, she would have canceled her appointment.

Instead, she wound up on an exam table at the Muscatine clinic listening to her baby’s heartbeat on a monitor and watching as Ms. Roman measured her belly.

“Nice job being perfect,” the midwife told her during the checkup.

Ms. Roman asked Ms. Tordai to describe her baby’s movements. “Constant,” she replied with a smile.

Ms. Roman asked whether she planned to breastfeed. Ms. Tordai said she didn’t have much luck with her first daughter, Aspen, now 4.

“Have you thought about a breastfeeding class?” the midwife asked.

“I don’t have time for that,” Ms. Tordai replied. Ms. Roman continued to coax her, noting where a breastfeeding class is available online.

Near the end of the appointment, Ms. Tordai asked Ms. Roman whether she could schedule an induced birth at the University of Iowa hospital. The midwife told her that, in general, letting labor begin on its own is better than artificially starting it.

But there was the matter of unreliable transportation. Ms. Tordai explained that scheduling the birth would help her arrange to have her mother drive her to the hospital in Iowa City. Ms. Roman agreed that transportation is a legitimate reason and arranged for an induced labor on Aug. 10.

The University of Iowa midwife team started offering services in 2020 in a clinic about 2 miles from Trinity Muscatine hospital. The hospital is owned by UnityPoint Health, a large nonprofit hospital system that blamed a lack of available obstetricians for the closure of the Muscatine birthing unit. At the time, UnityPoint leaders said they hoped to reopen the unit if they could recruit new obstetricians to the area.

Kristy Phillipson, a UnityPoint Health spokesperson, told KHN in June that the company has continued to try to recruit physicians, including for the Muscatine hospital. Although it has not reopened the birthing unit, the company regularly sends an obstetrician and other staff members to provide prenatal care and related services, she said.

Most pregnant patients from the area who choose UnityPoint for their care wind up giving birth at the system’s hospital in Bettendorf, a 45-minute drive to the east.

The University of Iowa midwife team has no plans to open its own birthing centers, but it hopes to expand its rural clinic service to other underserved towns. To do so, the university would need to hire more nurse-midwives, which could be a challenge. According to the Iowa Board of Nursing, 120 licensed nurse-midwives live in the state of 3 million people.

The University of Iowa plans to address that by starting the state’s first nurse-midwife training program in 2023. The master’s degree program, which will emphasize rural service, will train registered nurses to become nurse-midwives. It eventually could graduate eight people per year, said Amber Goodrich, a University of Iowa midwife helping lead the effort.

Those graduates could fill gaps throughout rural areas, where even more hospitals may shutter their birthing units in the coming years.

“This crisis is going nowhere fast,” Ms. Goodrich said.

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

Summer heat is notorious for making the strain of pregnancy worse. But for many pregnant people, sweltering temperatures are much worse than a sweaty annoyance.

New research shows that the risk of miscarriage rises sharply as the mercury climbs. In late August, for example, the risk of losing a pregnancy is 44% higher than in February, according to the findings.

“One of our hypotheses is that heat may trigger miscarriage, which is something that we are now exploring further,” says Amelia Wesselink, PhD, an assistant professor of epidemiology at Boston University School of Public Health, who led the study team. “Our next step is to dig into drivers of this seasonal pattern.”

She and her colleagues analyzed seasonal differences and pregnancy outcomes for over 12,000 women. Spontaneous abortion rates peaked in late August, especially for those living in the southern and midwestern United States.

Spontaneous abortion was defined as miscarriage, chemical pregnancy (a very early miscarriage where the embryo stops growing), or blighted ovum (the embryo stops developing or never develops).

From 2013 to 2020, 12,197 women living in the United States and Canada were followed for up to 1 year using Pregnancy Study Online (PRESTO), an internet-based fertility study from the Boston University School of Public Health. Those in the study answered questions about their income, education, race/ethnicity, and lifestyle, as well as follow-up questions about their pregnancy and/or loss of pregnancy.

Most of the people studied were non-Hispanic White (86%) and had at least a college degree (79%). Almost half earned more than $100,000 annually (47%). Those seeking fertility treatments were excluded from the study.

Half of the women (6,104) said they conceived in the first 12 months of trying to get pregnant, and almost one in five (19.5%) of those who conceived miscarried.

The risk of miscarriage was 44% higher in late August than it was in late February, the month with the lowest rate of lost pregnancies. This trend was almost exclusively seen for pregnancies in their first 8 weeks. The risk of miscarriage increased 31% in late August for pregnancies at any stage.

The link between miscarriage and extreme heat was strongest in the South and Midwest, with peaks in late August and early September, respectively.

“We know so little about the causes of miscarriage that it’s difficult to tie seasonal variation in risk to any particular cause,” says David Savitz, PhD, a professor of epidemiology and obstetrics, gynecology & pediatrics at Brown University, Providence, R.I., who helped conduct the study. “Exposures vary by summer, including a lower risk of respiratory infection in the warm season, changes in diet and physical activity, and physical factors such as temperature and sunlight.”

But another expert warned that extreme heat may not be the only culprit in summer’s observed miscarriage rates.

“You need to be careful when linking summer months to miscarriage, as women may pursue more outdoor activities during summer,” says Saifuddin Ahmed PhD, a researcher at Johns Hopkins Bloomberg School of Public Health, Baltimore.

Although the paper suggested physical activity may play a role in miscarriage frequency, no analysis supported this claim, Dr. Ahmed says.

Also, participants in the study were mostly White and tended to be wealthier than the general population, so the findings may not apply to everyone, Dr. Wesselink says. Although the researchers saw some similarities between participants with income above $100,000 a year and those who earned less, socioeconomic status plays an important role in environmental exposures – including heat – so the results may not hold among lower-income populations, Dr. Wesselink says.

Dr. Wesselink and her colleagues published their findings in the journal Epidemiology.

A version of this article first appeared on WebMD.com.

Summer heat is notorious for making the strain of pregnancy worse. But for many pregnant people, sweltering temperatures are much worse than a sweaty annoyance.

New research shows that the risk of miscarriage rises sharply as the mercury climbs. In late August, for example, the risk of losing a pregnancy is 44% higher than in February, according to the findings.

“One of our hypotheses is that heat may trigger miscarriage, which is something that we are now exploring further,” says Amelia Wesselink, PhD, an assistant professor of epidemiology at Boston University School of Public Health, who led the study team. “Our next step is to dig into drivers of this seasonal pattern.”

She and her colleagues analyzed seasonal differences and pregnancy outcomes for over 12,000 women. Spontaneous abortion rates peaked in late August, especially for those living in the southern and midwestern United States.

Spontaneous abortion was defined as miscarriage, chemical pregnancy (a very early miscarriage where the embryo stops growing), or blighted ovum (the embryo stops developing or never develops).

From 2013 to 2020, 12,197 women living in the United States and Canada were followed for up to 1 year using Pregnancy Study Online (PRESTO), an internet-based fertility study from the Boston University School of Public Health. Those in the study answered questions about their income, education, race/ethnicity, and lifestyle, as well as follow-up questions about their pregnancy and/or loss of pregnancy.

Most of the people studied were non-Hispanic White (86%) and had at least a college degree (79%). Almost half earned more than $100,000 annually (47%). Those seeking fertility treatments were excluded from the study.

Half of the women (6,104) said they conceived in the first 12 months of trying to get pregnant, and almost one in five (19.5%) of those who conceived miscarried.

The risk of miscarriage was 44% higher in late August than it was in late February, the month with the lowest rate of lost pregnancies. This trend was almost exclusively seen for pregnancies in their first 8 weeks. The risk of miscarriage increased 31% in late August for pregnancies at any stage.

The link between miscarriage and extreme heat was strongest in the South and Midwest, with peaks in late August and early September, respectively.

“We know so little about the causes of miscarriage that it’s difficult to tie seasonal variation in risk to any particular cause,” says David Savitz, PhD, a professor of epidemiology and obstetrics, gynecology & pediatrics at Brown University, Providence, R.I., who helped conduct the study. “Exposures vary by summer, including a lower risk of respiratory infection in the warm season, changes in diet and physical activity, and physical factors such as temperature and sunlight.”

But another expert warned that extreme heat may not be the only culprit in summer’s observed miscarriage rates.

“You need to be careful when linking summer months to miscarriage, as women may pursue more outdoor activities during summer,” says Saifuddin Ahmed PhD, a researcher at Johns Hopkins Bloomberg School of Public Health, Baltimore.

Although the paper suggested physical activity may play a role in miscarriage frequency, no analysis supported this claim, Dr. Ahmed says.

Also, participants in the study were mostly White and tended to be wealthier than the general population, so the findings may not apply to everyone, Dr. Wesselink says. Although the researchers saw some similarities between participants with income above $100,000 a year and those who earned less, socioeconomic status plays an important role in environmental exposures – including heat – so the results may not hold among lower-income populations, Dr. Wesselink says.

Dr. Wesselink and her colleagues published their findings in the journal Epidemiology.

A version of this article first appeared on WebMD.com.

Summer heat is notorious for making the strain of pregnancy worse. But for many pregnant people, sweltering temperatures are much worse than a sweaty annoyance.

New research shows that the risk of miscarriage rises sharply as the mercury climbs. In late August, for example, the risk of losing a pregnancy is 44% higher than in February, according to the findings.

“One of our hypotheses is that heat may trigger miscarriage, which is something that we are now exploring further,” says Amelia Wesselink, PhD, an assistant professor of epidemiology at Boston University School of Public Health, who led the study team. “Our next step is to dig into drivers of this seasonal pattern.”

She and her colleagues analyzed seasonal differences and pregnancy outcomes for over 12,000 women. Spontaneous abortion rates peaked in late August, especially for those living in the southern and midwestern United States.

Spontaneous abortion was defined as miscarriage, chemical pregnancy (a very early miscarriage where the embryo stops growing), or blighted ovum (the embryo stops developing or never develops).

From 2013 to 2020, 12,197 women living in the United States and Canada were followed for up to 1 year using Pregnancy Study Online (PRESTO), an internet-based fertility study from the Boston University School of Public Health. Those in the study answered questions about their income, education, race/ethnicity, and lifestyle, as well as follow-up questions about their pregnancy and/or loss of pregnancy.

Most of the people studied were non-Hispanic White (86%) and had at least a college degree (79%). Almost half earned more than $100,000 annually (47%). Those seeking fertility treatments were excluded from the study.

Half of the women (6,104) said they conceived in the first 12 months of trying to get pregnant, and almost one in five (19.5%) of those who conceived miscarried.

The risk of miscarriage was 44% higher in late August than it was in late February, the month with the lowest rate of lost pregnancies. This trend was almost exclusively seen for pregnancies in their first 8 weeks. The risk of miscarriage increased 31% in late August for pregnancies at any stage.

The link between miscarriage and extreme heat was strongest in the South and Midwest, with peaks in late August and early September, respectively.

“We know so little about the causes of miscarriage that it’s difficult to tie seasonal variation in risk to any particular cause,” says David Savitz, PhD, a professor of epidemiology and obstetrics, gynecology & pediatrics at Brown University, Providence, R.I., who helped conduct the study. “Exposures vary by summer, including a lower risk of respiratory infection in the warm season, changes in diet and physical activity, and physical factors such as temperature and sunlight.”

But another expert warned that extreme heat may not be the only culprit in summer’s observed miscarriage rates.

“You need to be careful when linking summer months to miscarriage, as women may pursue more outdoor activities during summer,” says Saifuddin Ahmed PhD, a researcher at Johns Hopkins Bloomberg School of Public Health, Baltimore.

Although the paper suggested physical activity may play a role in miscarriage frequency, no analysis supported this claim, Dr. Ahmed says.

Also, participants in the study were mostly White and tended to be wealthier than the general population, so the findings may not apply to everyone, Dr. Wesselink says. Although the researchers saw some similarities between participants with income above $100,000 a year and those who earned less, socioeconomic status plays an important role in environmental exposures – including heat – so the results may not hold among lower-income populations, Dr. Wesselink says.

Dr. Wesselink and her colleagues published their findings in the journal Epidemiology.

A version of this article first appeared on WebMD.com.

Married for nearly 5 years, Jessica King, 34, and her wife, Sarah, agreed on some things right from the start. “We always knew kids were in the equation,” Jessica says.

Now, Jessica is nearly 20 weeks pregnant, thanks to in vitro fertilization, or IVF. They did “reciprocal” IVF, with Sarah’s egg mixed with donor sperm and the embryo transferred into Jessica. “We’re excited – and terrified,” Jessica says.

But that terror goes beyond the typical concerns of excess weight gain and long labors. They live in Missouri, one of 13 states with so-called trigger laws that went into effect after the Supreme Court overturned Roe v. Wade and the constitutional right to abortion, giving states the power to regulate it. States with trigger laws either banned abortion immediately or within a specified time frame after the ruling. In all, 26 states are expected to have abortion restrictions.

Missouri now allows abortion only for medical emergencies. If her upcoming ultrasound shows serious issues, Jessica says they could easily travel to another state and pay for an abortion. She realizes not everyone can.

However, the concern about trigger laws goes well beyond abortion. Many experts worry about the “spill-over” effects the abortion laws – both the existing ones and future proposals – may have on fertility care and treatments.
 

‘Personhood’ laws drive the concern

“The current trigger laws on the books are not impacting people’s access to IVF,” says Barbara Collura, president and CEO of RESOLVE, an advocacy group for those with fertility issues. “What we are concerned about is they will come back and make them stronger.”

The chief concern for reproductive rights advocates is so-called “personhood” legislation. According to the Guttmacher Institute, at least six bills about personhood have been introduced in five states, including Iowa, Oklahoma, South Carolina, Vermont, and West Virginia. One of the two Oklahoma bills has gone the farthest, passed by one chamber.

Since the Guttmacher report, Ohio introduced its own personhood legislation July 11, recognizing the personhood of an unborn person from conception.

Personhood legislation defines a fertilized egg or embryo as a legal human entity, says Sean Tipton, chief policy and advocacy officer for the Washington-based American Society of Reproductive Medicine, a nonprofit advocacy group.

“If the legal status of fertilized eggs or early embryos is codified, in vitro fertilization procedures may become legally risky for patients, physicians and staff,” Mr. Tipton wrote in late June in Contemporary OB/GYN Journal. The American Society for Reproductive Medicine has posted a report on state abortion trigger laws and their potential implications for reproductive medicine. Of the 13 with trigger laws in effect, the report found concern about the potential effect on IVF only with Utah’s.
 

‘Safe’ states?

Even in states without trigger laws or personhood bills, IVF patients say they are anxious about how the Supreme Court ruling may ultimately affect care. Thanks to IVF, Shelly Battista and her husband Robert are expecting twins in December, little sisters to their daughter Emilia, who is 2½.

They live in Illinois, where abortion is legal. “Even though we are safe now, I think the overturning of Roe has made it clear to all of us that none of our freedoms are safe, especially reproductive rights,” Ms. Shelly says.

About one in eight U.S. couples are infertile, according to RESOLVE, In 2019, 2% of all babies born in the United States, or about 78,000 infants, were conceived with the use of assisted reproductive technologies, according to the Centers for Disease Control and Prevention. The most common assisted reproductive technology is IVF, in which the sperm fertilizes the egg outside the body and an embryo is then transferred. The standard of practice is to transfer a single embryo, freezing others for future use.
 

Trigger state doctors weigh in

Some fertility doctors in those “trigger” states are keeping a close eye on proposed legislation and talking to legislators for interpretation of current and proposed laws.

Eli Reshef, MD, a reproductive endocrinologist and fertility specialist at Bennett Fertility Institute in Oklahoma City, notes that his state has “the strictest abortion law in the land.” The law prohibits all abortions with few exceptions, such as the removal of an ectopic pregnancy (when a fertilized egg implants outside the uterus, such as in the fallopian tubes).

While IVF will not be affected for now, he worries that the Oklahoma law allows a private citizen to sue a health care provider that they feel is performing abortion. The Oklahoma law leaves interpretation of abortion up to the general public, who may be unfamiliar with the language of the law, House Bill 4327.

Dean Moutos, MD, a reproductive endocrinologist and medical director of Arkansas Fertility and Gynecology in Little Rock, says his state’s current trigger law should not affect IVF. “When you read the bill, it says abortion means to terminate the pregnancy of a woman.” Still, he says, “we are concerned about what might happen in the future” and the possibility that some legislators may interpret that differently.
 

A minority approach

John David Gordon, MD, a reproductive endocrinologist and medical director of Southeastern Fertility Center for Fertility and Reproductive Surgery in Knoxville, Tenn., is also in a trigger state. However, it’s not likely any personhood laws would affect his practice.

That’s because his center, which he acknowledges is clearly in the minority, only performs natural-cycle IVF, which usually results in a single egg, or “mini-stim IVF,” which usually results in three to eight eggs in order to limit the number that may be potentially fertilized. Often, he says, patients choose to freeze unfertilized eggs (alone) to avoid creating an excessive number of embryos. He has a “no discard” program, with any viable embryos frozen or transferred. Abandoned embryos are donated to others.

“This may work for young women,” says Marcelle Cedars, MD, director of reproductive endocrinology at the University of California, San Francisco, and president of the American Society of Reproductive Medicine. However, she says, it will be very inefficient for older patients, since they have a higher percentage of abnormal eggs.

Overall, that approach will also drive up costs, especially for older women, Dr. Cedars says. An average cycle of IVF costs $12,400, and most Americans’ insurance plans don’t cover IVF, according to Mr. Tipton.
 

Top concerns for IVF

“Personhood” legislation has the potential to upend many common IVF practices, experts say.

Of greatest concern to fertility practices are potential restrictions on the freezing or discarding of embryos, Dr. Cedars says. “This could have a critical impact on practicing the safest, most evidence-based medicine,” she says.

Most children born in the United States as a result of IVF procedures are born from frozen embryos, according to the Society for Assisted Reproductive Technology, an organization for reproductive specialists.

“The practice of IVF really requires that we generate more embryos than will be used in a given [IVF] cycle,” agrees Kara Goldman, MD, associate professor of obstetrics and gynecology and medical director of the fertility preservation program at Northwestern University, Chicago. She performed the embryo transfer for the Battistas.

In nature, she says, it’s known that only a small number of eggs will be competent to generate a baby. “We see the same thing in IVF.” In a single cycle, 20 eggs may be retrieved, but many fewer typically reach successful fertilization and are able to be implanted.

When patients have completed their family, unused embryos are donated to research, donated for adoption, or destroyed. If embryo destruction is outlawed, Dr. Goldman says, it will have serious ramifications for the practice of IVF.

And if personhood legislation prohibits destroying any embryos, others wonder: Would a lab technician who accidentally dropped and destroyed an embryo be subject to charges? If laws prohibit destruction of embryos, others wonder if will families be forced to pay the embryo storage fees, generally $500-$1,000 a year, in perpetuity.

If an embryo is declared a person, it could also affect a practice called preimplantation genetic testing, or PGT. In PGT, cells are retrieved from an embryo and checked for genetic disorders such as sickle cell anemia and cystic fibrosis, with some parents choosing to discard embryos that are found to be affected.

Some potential parents choose this testing because they know they are carriers for genetic diseases that are serious and even incompatible with life, says Art Caplan, PhD, head of the division of medical ethics at New York University. They may choose to discard embryos that show evidence of the diseases.

Also under fire could be “selective reduction,” reducing multiple fetuses to a single or twin, to reduce risks to babies and mother.

Dr. Caplan predicts if states have many restrictions, some providers will adopt the attitude that “if no one reports, it did not happen.” And those prospective parents with the means, he says, will go to court and fight restrictions. “When they do it, they are saying, ‘You say you are pro-life; I’m trying to have a child. What are you doing getting in my way?’”
 

IVF families: Tough decisions, emotional times

The Battistas, of Illinois, have had an especially rough road. Shelly was diagnosed with a fast-growing breast cancer in 2020, when Emilia was just an infant. Warned that the chemotherapy she needed would suppress her ovaries, Shelly underwent egg retrieval before starting the cancer treatment.

She opted to have a double mastectomy and her ovaries removed after learning she carried the BRCA1 genetic mutation, boosting the risk of both breast and ovarian cancer.

Once she was cancer-free, she was cleared to start IVF. The first two embryo transfers failed. The third transfer, of a single embryo, was successful. But it split, a rare occurrence, producing two embryos. “It was a big shock, but in the best way,” she says about learning they were having twins. “Now we are over the moon.”

Five frozen embryos remain. At the start, the Battistas decided to discard unused embryos. She and Robert are discussing what to do next. If they decide they are done building their family after the twins’ birth, she wonders, “do we need to discard our [other] embryos before that becomes something that isn’t eligible [possible] for us any longer?” She doesn’t want to be rushed into that decision, however, especially with her medical history.

Jessica King and Sarah have 20 more embryos.

The couple had decided to donate unused embryos for research, when the time comes, and for different reasons. Her wife’s decision is based on her belief in science, while Jessica cites her faith. “As a Jew, it is part of our faith, that we should be doing everything we can to advance humanity,” she says.

In the midst of all the uncertainty, Jessica says, only half-jokingly, that she is tempted to claim the frozen embryos as dependents. “If you are truly going to claim these are precious human lives, you should be giving me all the benefits from having children,” she says.

Shelly knows that having one daughter, with two more on the way, affects her thinking about the court’s ruling. “My overall wish would be that Roe v. Wade is reinstated, and my daughters have the same rights and options that I have … or I did have until my current 36 years of life.”

A version of this article first appeared on WebMD.com.

Married for nearly 5 years, Jessica King, 34, and her wife, Sarah, agreed on some things right from the start. “We always knew kids were in the equation,” Jessica says.

Now, Jessica is nearly 20 weeks pregnant, thanks to in vitro fertilization, or IVF. They did “reciprocal” IVF, with Sarah’s egg mixed with donor sperm and the embryo transferred into Jessica. “We’re excited – and terrified,” Jessica says.

But that terror goes beyond the typical concerns of excess weight gain and long labors. They live in Missouri, one of 13 states with so-called trigger laws that went into effect after the Supreme Court overturned Roe v. Wade and the constitutional right to abortion, giving states the power to regulate it. States with trigger laws either banned abortion immediately or within a specified time frame after the ruling. In all, 26 states are expected to have abortion restrictions.

Missouri now allows abortion only for medical emergencies. If her upcoming ultrasound shows serious issues, Jessica says they could easily travel to another state and pay for an abortion. She realizes not everyone can.

However, the concern about trigger laws goes well beyond abortion. Many experts worry about the “spill-over” effects the abortion laws – both the existing ones and future proposals – may have on fertility care and treatments.
 

‘Personhood’ laws drive the concern

“The current trigger laws on the books are not impacting people’s access to IVF,” says Barbara Collura, president and CEO of RESOLVE, an advocacy group for those with fertility issues. “What we are concerned about is they will come back and make them stronger.”

The chief concern for reproductive rights advocates is so-called “personhood” legislation. According to the Guttmacher Institute, at least six bills about personhood have been introduced in five states, including Iowa, Oklahoma, South Carolina, Vermont, and West Virginia. One of the two Oklahoma bills has gone the farthest, passed by one chamber.

Since the Guttmacher report, Ohio introduced its own personhood legislation July 11, recognizing the personhood of an unborn person from conception.

Personhood legislation defines a fertilized egg or embryo as a legal human entity, says Sean Tipton, chief policy and advocacy officer for the Washington-based American Society of Reproductive Medicine, a nonprofit advocacy group.

“If the legal status of fertilized eggs or early embryos is codified, in vitro fertilization procedures may become legally risky for patients, physicians and staff,” Mr. Tipton wrote in late June in Contemporary OB/GYN Journal. The American Society for Reproductive Medicine has posted a report on state abortion trigger laws and their potential implications for reproductive medicine. Of the 13 with trigger laws in effect, the report found concern about the potential effect on IVF only with Utah’s.
 

‘Safe’ states?

Even in states without trigger laws or personhood bills, IVF patients say they are anxious about how the Supreme Court ruling may ultimately affect care. Thanks to IVF, Shelly Battista and her husband Robert are expecting twins in December, little sisters to their daughter Emilia, who is 2½.

They live in Illinois, where abortion is legal. “Even though we are safe now, I think the overturning of Roe has made it clear to all of us that none of our freedoms are safe, especially reproductive rights,” Ms. Shelly says.

About one in eight U.S. couples are infertile, according to RESOLVE, In 2019, 2% of all babies born in the United States, or about 78,000 infants, were conceived with the use of assisted reproductive technologies, according to the Centers for Disease Control and Prevention. The most common assisted reproductive technology is IVF, in which the sperm fertilizes the egg outside the body and an embryo is then transferred. The standard of practice is to transfer a single embryo, freezing others for future use.
 

Trigger state doctors weigh in

Some fertility doctors in those “trigger” states are keeping a close eye on proposed legislation and talking to legislators for interpretation of current and proposed laws.

Eli Reshef, MD, a reproductive endocrinologist and fertility specialist at Bennett Fertility Institute in Oklahoma City, notes that his state has “the strictest abortion law in the land.” The law prohibits all abortions with few exceptions, such as the removal of an ectopic pregnancy (when a fertilized egg implants outside the uterus, such as in the fallopian tubes).

While IVF will not be affected for now, he worries that the Oklahoma law allows a private citizen to sue a health care provider that they feel is performing abortion. The Oklahoma law leaves interpretation of abortion up to the general public, who may be unfamiliar with the language of the law, House Bill 4327.

Dean Moutos, MD, a reproductive endocrinologist and medical director of Arkansas Fertility and Gynecology in Little Rock, says his state’s current trigger law should not affect IVF. “When you read the bill, it says abortion means to terminate the pregnancy of a woman.” Still, he says, “we are concerned about what might happen in the future” and the possibility that some legislators may interpret that differently.
 

A minority approach

John David Gordon, MD, a reproductive endocrinologist and medical director of Southeastern Fertility Center for Fertility and Reproductive Surgery in Knoxville, Tenn., is also in a trigger state. However, it’s not likely any personhood laws would affect his practice.

That’s because his center, which he acknowledges is clearly in the minority, only performs natural-cycle IVF, which usually results in a single egg, or “mini-stim IVF,” which usually results in three to eight eggs in order to limit the number that may be potentially fertilized. Often, he says, patients choose to freeze unfertilized eggs (alone) to avoid creating an excessive number of embryos. He has a “no discard” program, with any viable embryos frozen or transferred. Abandoned embryos are donated to others.

“This may work for young women,” says Marcelle Cedars, MD, director of reproductive endocrinology at the University of California, San Francisco, and president of the American Society of Reproductive Medicine. However, she says, it will be very inefficient for older patients, since they have a higher percentage of abnormal eggs.

Overall, that approach will also drive up costs, especially for older women, Dr. Cedars says. An average cycle of IVF costs $12,400, and most Americans’ insurance plans don’t cover IVF, according to Mr. Tipton.
 

Top concerns for IVF

“Personhood” legislation has the potential to upend many common IVF practices, experts say.

Of greatest concern to fertility practices are potential restrictions on the freezing or discarding of embryos, Dr. Cedars says. “This could have a critical impact on practicing the safest, most evidence-based medicine,” she says.

Most children born in the United States as a result of IVF procedures are born from frozen embryos, according to the Society for Assisted Reproductive Technology, an organization for reproductive specialists.

“The practice of IVF really requires that we generate more embryos than will be used in a given [IVF] cycle,” agrees Kara Goldman, MD, associate professor of obstetrics and gynecology and medical director of the fertility preservation program at Northwestern University, Chicago. She performed the embryo transfer for the Battistas.

In nature, she says, it’s known that only a small number of eggs will be competent to generate a baby. “We see the same thing in IVF.” In a single cycle, 20 eggs may be retrieved, but many fewer typically reach successful fertilization and are able to be implanted.

When patients have completed their family, unused embryos are donated to research, donated for adoption, or destroyed. If embryo destruction is outlawed, Dr. Goldman says, it will have serious ramifications for the practice of IVF.

And if personhood legislation prohibits destroying any embryos, others wonder: Would a lab technician who accidentally dropped and destroyed an embryo be subject to charges? If laws prohibit destruction of embryos, others wonder if will families be forced to pay the embryo storage fees, generally $500-$1,000 a year, in perpetuity.

If an embryo is declared a person, it could also affect a practice called preimplantation genetic testing, or PGT. In PGT, cells are retrieved from an embryo and checked for genetic disorders such as sickle cell anemia and cystic fibrosis, with some parents choosing to discard embryos that are found to be affected.

Some potential parents choose this testing because they know they are carriers for genetic diseases that are serious and even incompatible with life, says Art Caplan, PhD, head of the division of medical ethics at New York University. They may choose to discard embryos that show evidence of the diseases.

Also under fire could be “selective reduction,” reducing multiple fetuses to a single or twin, to reduce risks to babies and mother.

Dr. Caplan predicts if states have many restrictions, some providers will adopt the attitude that “if no one reports, it did not happen.” And those prospective parents with the means, he says, will go to court and fight restrictions. “When they do it, they are saying, ‘You say you are pro-life; I’m trying to have a child. What are you doing getting in my way?’”
 

IVF families: Tough decisions, emotional times

The Battistas, of Illinois, have had an especially rough road. Shelly was diagnosed with a fast-growing breast cancer in 2020, when Emilia was just an infant. Warned that the chemotherapy she needed would suppress her ovaries, Shelly underwent egg retrieval before starting the cancer treatment.

She opted to have a double mastectomy and her ovaries removed after learning she carried the BRCA1 genetic mutation, boosting the risk of both breast and ovarian cancer.

Once she was cancer-free, she was cleared to start IVF. The first two embryo transfers failed. The third transfer, of a single embryo, was successful. But it split, a rare occurrence, producing two embryos. “It was a big shock, but in the best way,” she says about learning they were having twins. “Now we are over the moon.”

Five frozen embryos remain. At the start, the Battistas decided to discard unused embryos. She and Robert are discussing what to do next. If they decide they are done building their family after the twins’ birth, she wonders, “do we need to discard our [other] embryos before that becomes something that isn’t eligible [possible] for us any longer?” She doesn’t want to be rushed into that decision, however, especially with her medical history.

Jessica King and Sarah have 20 more embryos.

The couple had decided to donate unused embryos for research, when the time comes, and for different reasons. Her wife’s decision is based on her belief in science, while Jessica cites her faith. “As a Jew, it is part of our faith, that we should be doing everything we can to advance humanity,” she says.

In the midst of all the uncertainty, Jessica says, only half-jokingly, that she is tempted to claim the frozen embryos as dependents. “If you are truly going to claim these are precious human lives, you should be giving me all the benefits from having children,” she says.

Shelly knows that having one daughter, with two more on the way, affects her thinking about the court’s ruling. “My overall wish would be that Roe v. Wade is reinstated, and my daughters have the same rights and options that I have … or I did have until my current 36 years of life.”

A version of this article first appeared on WebMD.com.

Married for nearly 5 years, Jessica King, 34, and her wife, Sarah, agreed on some things right from the start. “We always knew kids were in the equation,” Jessica says.

Now, Jessica is nearly 20 weeks pregnant, thanks to in vitro fertilization, or IVF. They did “reciprocal” IVF, with Sarah’s egg mixed with donor sperm and the embryo transferred into Jessica. “We’re excited – and terrified,” Jessica says.

But that terror goes beyond the typical concerns of excess weight gain and long labors. They live in Missouri, one of 13 states with so-called trigger laws that went into effect after the Supreme Court overturned Roe v. Wade and the constitutional right to abortion, giving states the power to regulate it. States with trigger laws either banned abortion immediately or within a specified time frame after the ruling. In all, 26 states are expected to have abortion restrictions.

Missouri now allows abortion only for medical emergencies. If her upcoming ultrasound shows serious issues, Jessica says they could easily travel to another state and pay for an abortion. She realizes not everyone can.

However, the concern about trigger laws goes well beyond abortion. Many experts worry about the “spill-over” effects the abortion laws – both the existing ones and future proposals – may have on fertility care and treatments.
 

‘Personhood’ laws drive the concern

“The current trigger laws on the books are not impacting people’s access to IVF,” says Barbara Collura, president and CEO of RESOLVE, an advocacy group for those with fertility issues. “What we are concerned about is they will come back and make them stronger.”

The chief concern for reproductive rights advocates is so-called “personhood” legislation. According to the Guttmacher Institute, at least six bills about personhood have been introduced in five states, including Iowa, Oklahoma, South Carolina, Vermont, and West Virginia. One of the two Oklahoma bills has gone the farthest, passed by one chamber.

Since the Guttmacher report, Ohio introduced its own personhood legislation July 11, recognizing the personhood of an unborn person from conception.

Personhood legislation defines a fertilized egg or embryo as a legal human entity, says Sean Tipton, chief policy and advocacy officer for the Washington-based American Society of Reproductive Medicine, a nonprofit advocacy group.

“If the legal status of fertilized eggs or early embryos is codified, in vitro fertilization procedures may become legally risky for patients, physicians and staff,” Mr. Tipton wrote in late June in Contemporary OB/GYN Journal. The American Society for Reproductive Medicine has posted a report on state abortion trigger laws and their potential implications for reproductive medicine. Of the 13 with trigger laws in effect, the report found concern about the potential effect on IVF only with Utah’s.
 

‘Safe’ states?

Even in states without trigger laws or personhood bills, IVF patients say they are anxious about how the Supreme Court ruling may ultimately affect care. Thanks to IVF, Shelly Battista and her husband Robert are expecting twins in December, little sisters to their daughter Emilia, who is 2½.

They live in Illinois, where abortion is legal. “Even though we are safe now, I think the overturning of Roe has made it clear to all of us that none of our freedoms are safe, especially reproductive rights,” Ms. Shelly says.

About one in eight U.S. couples are infertile, according to RESOLVE, In 2019, 2% of all babies born in the United States, or about 78,000 infants, were conceived with the use of assisted reproductive technologies, according to the Centers for Disease Control and Prevention. The most common assisted reproductive technology is IVF, in which the sperm fertilizes the egg outside the body and an embryo is then transferred. The standard of practice is to transfer a single embryo, freezing others for future use.
 

Trigger state doctors weigh in

Some fertility doctors in those “trigger” states are keeping a close eye on proposed legislation and talking to legislators for interpretation of current and proposed laws.

Eli Reshef, MD, a reproductive endocrinologist and fertility specialist at Bennett Fertility Institute in Oklahoma City, notes that his state has “the strictest abortion law in the land.” The law prohibits all abortions with few exceptions, such as the removal of an ectopic pregnancy (when a fertilized egg implants outside the uterus, such as in the fallopian tubes).

While IVF will not be affected for now, he worries that the Oklahoma law allows a private citizen to sue a health care provider that they feel is performing abortion. The Oklahoma law leaves interpretation of abortion up to the general public, who may be unfamiliar with the language of the law, House Bill 4327.

Dean Moutos, MD, a reproductive endocrinologist and medical director of Arkansas Fertility and Gynecology in Little Rock, says his state’s current trigger law should not affect IVF. “When you read the bill, it says abortion means to terminate the pregnancy of a woman.” Still, he says, “we are concerned about what might happen in the future” and the possibility that some legislators may interpret that differently.
 

A minority approach

John David Gordon, MD, a reproductive endocrinologist and medical director of Southeastern Fertility Center for Fertility and Reproductive Surgery in Knoxville, Tenn., is also in a trigger state. However, it’s not likely any personhood laws would affect his practice.

That’s because his center, which he acknowledges is clearly in the minority, only performs natural-cycle IVF, which usually results in a single egg, or “mini-stim IVF,” which usually results in three to eight eggs in order to limit the number that may be potentially fertilized. Often, he says, patients choose to freeze unfertilized eggs (alone) to avoid creating an excessive number of embryos. He has a “no discard” program, with any viable embryos frozen or transferred. Abandoned embryos are donated to others.

“This may work for young women,” says Marcelle Cedars, MD, director of reproductive endocrinology at the University of California, San Francisco, and president of the American Society of Reproductive Medicine. However, she says, it will be very inefficient for older patients, since they have a higher percentage of abnormal eggs.

Overall, that approach will also drive up costs, especially for older women, Dr. Cedars says. An average cycle of IVF costs $12,400, and most Americans’ insurance plans don’t cover IVF, according to Mr. Tipton.
 

Top concerns for IVF

“Personhood” legislation has the potential to upend many common IVF practices, experts say.

Of greatest concern to fertility practices are potential restrictions on the freezing or discarding of embryos, Dr. Cedars says. “This could have a critical impact on practicing the safest, most evidence-based medicine,” she says.

Most children born in the United States as a result of IVF procedures are born from frozen embryos, according to the Society for Assisted Reproductive Technology, an organization for reproductive specialists.

“The practice of IVF really requires that we generate more embryos than will be used in a given [IVF] cycle,” agrees Kara Goldman, MD, associate professor of obstetrics and gynecology and medical director of the fertility preservation program at Northwestern University, Chicago. She performed the embryo transfer for the Battistas.

In nature, she says, it’s known that only a small number of eggs will be competent to generate a baby. “We see the same thing in IVF.” In a single cycle, 20 eggs may be retrieved, but many fewer typically reach successful fertilization and are able to be implanted.

When patients have completed their family, unused embryos are donated to research, donated for adoption, or destroyed. If embryo destruction is outlawed, Dr. Goldman says, it will have serious ramifications for the practice of IVF.

And if personhood legislation prohibits destroying any embryos, others wonder: Would a lab technician who accidentally dropped and destroyed an embryo be subject to charges? If laws prohibit destruction of embryos, others wonder if will families be forced to pay the embryo storage fees, generally $500-$1,000 a year, in perpetuity.

If an embryo is declared a person, it could also affect a practice called preimplantation genetic testing, or PGT. In PGT, cells are retrieved from an embryo and checked for genetic disorders such as sickle cell anemia and cystic fibrosis, with some parents choosing to discard embryos that are found to be affected.

Some potential parents choose this testing because they know they are carriers for genetic diseases that are serious and even incompatible with life, says Art Caplan, PhD, head of the division of medical ethics at New York University. They may choose to discard embryos that show evidence of the diseases.

Also under fire could be “selective reduction,” reducing multiple fetuses to a single or twin, to reduce risks to babies and mother.

Dr. Caplan predicts if states have many restrictions, some providers will adopt the attitude that “if no one reports, it did not happen.” And those prospective parents with the means, he says, will go to court and fight restrictions. “When they do it, they are saying, ‘You say you are pro-life; I’m trying to have a child. What are you doing getting in my way?’”
 

IVF families: Tough decisions, emotional times

The Battistas, of Illinois, have had an especially rough road. Shelly was diagnosed with a fast-growing breast cancer in 2020, when Emilia was just an infant. Warned that the chemotherapy she needed would suppress her ovaries, Shelly underwent egg retrieval before starting the cancer treatment.

She opted to have a double mastectomy and her ovaries removed after learning she carried the BRCA1 genetic mutation, boosting the risk of both breast and ovarian cancer.

Once she was cancer-free, she was cleared to start IVF. The first two embryo transfers failed. The third transfer, of a single embryo, was successful. But it split, a rare occurrence, producing two embryos. “It was a big shock, but in the best way,” she says about learning they were having twins. “Now we are over the moon.”

Five frozen embryos remain. At the start, the Battistas decided to discard unused embryos. She and Robert are discussing what to do next. If they decide they are done building their family after the twins’ birth, she wonders, “do we need to discard our [other] embryos before that becomes something that isn’t eligible [possible] for us any longer?” She doesn’t want to be rushed into that decision, however, especially with her medical history.

Jessica King and Sarah have 20 more embryos.

The couple had decided to donate unused embryos for research, when the time comes, and for different reasons. Her wife’s decision is based on her belief in science, while Jessica cites her faith. “As a Jew, it is part of our faith, that we should be doing everything we can to advance humanity,” she says.

In the midst of all the uncertainty, Jessica says, only half-jokingly, that she is tempted to claim the frozen embryos as dependents. “If you are truly going to claim these are precious human lives, you should be giving me all the benefits from having children,” she says.

Shelly knows that having one daughter, with two more on the way, affects her thinking about the court’s ruling. “My overall wish would be that Roe v. Wade is reinstated, and my daughters have the same rights and options that I have … or I did have until my current 36 years of life.”

A version of this article first appeared on WebMD.com.

Will your health plan pay for an abortion now that the Supreme Court has overturned Roe v. Wade?

Even before the June 24 ruling, insurance coverage for abortion varied widely. Now the issue is even more complex as states set varying rules – about half are expected to limit or ban abortion in almost all circumstances.

To be clear, though, the question of whether an insurance plan covers abortion is not the same as whether abortion is allowed in a state. Coverage issues are more complicated and governed by a wide variety of factors, including the level of abortion access a state allows.

How dense a thicket is it? Abortion may be covered by a health plan, but if no providers are available, patients don’t have access. However, people with insurance that does not cover abortion can still get one – but only if it’s available in their states or they can afford to travel and pay out of pocket. There are also a host of unanswered questions about whether states that restrict abortion will have the legal authority to target abortion coverage in employer plans.

The issues will likely be before the courts for years to come.

“States will pass laws, there will be some conflict, and then it goes to the courts,” said Erin Fuse Brown, director of the Center for Law, Health & Society at the Georgia State University, Atlanta. “It could be a while.”

In the meantime, here are answers to three common questions.
 

Are health plans – or employers – required to offer coverage for elective abortions?

The simple answer is “no.”

“There’s no law that requires any health plan, employer-based or anything else, to cover an elective abortion,” Ms. Fuse Brown said.

Whether they do is more complicated.

Some job-based health plans cover elective abortions. Patients can search their plan documents or call their insurers directly to check.

Coverage is more likely in plans offered by self-insured employers because a federal pensions law generally preempts state regulation of those health plans. Self-funded employers, which tend to be the larger ones, pay the medical bills, although they generally hire third parties, sometimes health insurers, to handle claims and administrative work.

Still, millions of Americans work for smaller employers, which tend to buy plans directly from health insurers, which then pay the medical bills. Those plans, known as “fully insured,” are subject to state laws, whose approaches to abortion coverage have long varied.

Eleven states bar those private plans from covering abortion in most circumstances, according to KFF, although some of the states allow consumers to purchase an insurance rider that would cover abortion costs.

If you’re not sure what type of health plan you have, ask the administrators.

“There is no way to tell from the face of your insurance card if you are fully insured or self-funded,” Ms. Fuse Brown said.

For the more than 14 million Americans who buy their coverage through the Affordable Care Act marketplaces, their state of residence is key.

Twenty-six states restrict abortion coverage in ACA plans, while seven states require it as a plan benefit, according to KFF. Those states are California, Illinois, Maine, Maryland, New York, Oregon, and Washington.

The rules for Medicaid, the federal-state health program for people with low incomes, also vary. Thirty-four states and the District of Columbia follow the so-called Hyde Amendment, which bars federal funds from paying for abortions, except in cases of rape or incest or to save the life of the mother, although some states allow coverage for other medically necessary abortions.

For all those reasons, it’s not surprising that research published in the journal Health Affairs noted that patients paid out-of-pocket for the majority of abortions (69% in one study). The researchers found that the median cost of a medication abortion was $560 and that abortion procedures ranged from a median of $575 in the first trimester to $895 in the second.
 

What about coverage for pregnancy-related complications that require treatment similar to abortion?

Insurance policies must cover care for essential health services, including medically necessary pregnancy care and abortion when carrying a pregnancy to term would endanger a patient’s life.

Under the Pregnancy Discrimination Act of 1978 and other rules, Ms. Fuse Brown said, “pregnancy and prenatal care, including high-risk pregnancies, and obstetric care in general is required to be covered.”

In an ectopic pregnancy – when a fertilized egg implants outside the uterus – the embryo is not viable, and the condition is generally life-threatening to the mother without medical treatment. Many other scenarios could come into play, including situations in which a woman has a miscarriage but not all the tissue is expelled, potentially leading to a dangerous infection.

Although all state laws that currently restrict abortion include an exception to save the life of the mother, what constitutes a life-threatening scenario is not always clear. That means physicians in abortion-ban states may have to weigh the pregnant person’s medical risk against possible legal ramifications.

“This is less of a coverage question and more of a question of whether providers in the states that ban abortion are going to provide the care,” said Katie Keith, a research faculty member at the Center on Health Insurance Reforms at Georgetown University, Washington. “All of these laws are designed to chill behavior, to make it so unattractive or scary to providers to keep them from doing it at all.”
 

Can residents of states where abortion is illegal get coverage in other states or help with travel costs?

In recent weeks, many large employers – including Microsoft, Bank of America, Disney, and Netflix – have said they will set up programs to help pay travel costs so workers or other beneficiaries in states with bans can travel to get an abortion elsewhere.

But it isn’t as straightforward as it sounds. Employers will have to figure out whether workers will access this benefit through the health plan or some other reimbursement method. Protecting privacy, too, may be an issue. Some consultants also said employers will need to consider whether their travel reimbursement benefit conflicts with other rules. If an employer, for example, covers travel for abortion procedures but not for an eating disorder clinic, does that violate the Mental Health Parity and Addiction Equity Act? If a plan has no providers willing or able to do abortions, does it violate any state or federal network adequacy rules?

Lawmakers need to think about these conflicts, said Jessica Waltman, vice president for compliance at employee benefits company MZQ Consulting. “They could be putting all the employer group plans in their state in a very precarious position if that state law would prohibit them from complying with federal law,” particularly if they restrict access to benefits called for in the Pregnancy Discrimination Act.

There are other potential conflicts if an employer is in a state that allows abortion but a worker is in a state that restricts it. “If I’m an Oregon-based company, my insurance plan must provide for abortion coverage, but what do I do about an Oklahoma employee? I don’t know the answer,” said René Thorne, a principal at Jackson Lewis, where she oversees litigation that involves self-insured firms.

Also uncertain is whether state laws will take aim at insurers, employers, or others that offer benefits, including travel or televisits, for abortion services.

Laws that restrict abortion, Ms. Thorne wrote in a white paper for clients, generally apply to the medical provider and sometimes those who “aid or abet” the abortion. Some states, including Texas, allow private citizens to sue for $10,000 anyone who provides an illegal abortion or helps a person access an abortion.

Whether those laws will be applied to employers or insurers will undoubtedly end up in the courts.

“We are in uncharted territory here, as we’ve never before been in a situation where plans, as well as their employer sponsors and those administering the plans, might face criminal liability in connection with a plan benefit,” said Seth Perretta, a principal at the Groom Law Group, which advises employers.

Answers won’t come soon, but “there will be so much litigation around this,” said Ms. Thorne.

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

Will your health plan pay for an abortion now that the Supreme Court has overturned Roe v. Wade?

Even before the June 24 ruling, insurance coverage for abortion varied widely. Now the issue is even more complex as states set varying rules – about half are expected to limit or ban abortion in almost all circumstances.

To be clear, though, the question of whether an insurance plan covers abortion is not the same as whether abortion is allowed in a state. Coverage issues are more complicated and governed by a wide variety of factors, including the level of abortion access a state allows.

How dense a thicket is it? Abortion may be covered by a health plan, but if no providers are available, patients don’t have access. However, people with insurance that does not cover abortion can still get one – but only if it’s available in their states or they can afford to travel and pay out of pocket. There are also a host of unanswered questions about whether states that restrict abortion will have the legal authority to target abortion coverage in employer plans.

The issues will likely be before the courts for years to come.

“States will pass laws, there will be some conflict, and then it goes to the courts,” said Erin Fuse Brown, director of the Center for Law, Health & Society at the Georgia State University, Atlanta. “It could be a while.”

In the meantime, here are answers to three common questions.
 

Are health plans – or employers – required to offer coverage for elective abortions?

The simple answer is “no.”

“There’s no law that requires any health plan, employer-based or anything else, to cover an elective abortion,” Ms. Fuse Brown said.

Whether they do is more complicated.

Some job-based health plans cover elective abortions. Patients can search their plan documents or call their insurers directly to check.

Coverage is more likely in plans offered by self-insured employers because a federal pensions law generally preempts state regulation of those health plans. Self-funded employers, which tend to be the larger ones, pay the medical bills, although they generally hire third parties, sometimes health insurers, to handle claims and administrative work.

Still, millions of Americans work for smaller employers, which tend to buy plans directly from health insurers, which then pay the medical bills. Those plans, known as “fully insured,” are subject to state laws, whose approaches to abortion coverage have long varied.

Eleven states bar those private plans from covering abortion in most circumstances, according to KFF, although some of the states allow consumers to purchase an insurance rider that would cover abortion costs.

If you’re not sure what type of health plan you have, ask the administrators.

“There is no way to tell from the face of your insurance card if you are fully insured or self-funded,” Ms. Fuse Brown said.

For the more than 14 million Americans who buy their coverage through the Affordable Care Act marketplaces, their state of residence is key.

Twenty-six states restrict abortion coverage in ACA plans, while seven states require it as a plan benefit, according to KFF. Those states are California, Illinois, Maine, Maryland, New York, Oregon, and Washington.

The rules for Medicaid, the federal-state health program for people with low incomes, also vary. Thirty-four states and the District of Columbia follow the so-called Hyde Amendment, which bars federal funds from paying for abortions, except in cases of rape or incest or to save the life of the mother, although some states allow coverage for other medically necessary abortions.

For all those reasons, it’s not surprising that research published in the journal Health Affairs noted that patients paid out-of-pocket for the majority of abortions (69% in one study). The researchers found that the median cost of a medication abortion was $560 and that abortion procedures ranged from a median of $575 in the first trimester to $895 in the second.
 

What about coverage for pregnancy-related complications that require treatment similar to abortion?

Insurance policies must cover care for essential health services, including medically necessary pregnancy care and abortion when carrying a pregnancy to term would endanger a patient’s life.

Under the Pregnancy Discrimination Act of 1978 and other rules, Ms. Fuse Brown said, “pregnancy and prenatal care, including high-risk pregnancies, and obstetric care in general is required to be covered.”

In an ectopic pregnancy – when a fertilized egg implants outside the uterus – the embryo is not viable, and the condition is generally life-threatening to the mother without medical treatment. Many other scenarios could come into play, including situations in which a woman has a miscarriage but not all the tissue is expelled, potentially leading to a dangerous infection.

Although all state laws that currently restrict abortion include an exception to save the life of the mother, what constitutes a life-threatening scenario is not always clear. That means physicians in abortion-ban states may have to weigh the pregnant person’s medical risk against possible legal ramifications.

“This is less of a coverage question and more of a question of whether providers in the states that ban abortion are going to provide the care,” said Katie Keith, a research faculty member at the Center on Health Insurance Reforms at Georgetown University, Washington. “All of these laws are designed to chill behavior, to make it so unattractive or scary to providers to keep them from doing it at all.”
 

Can residents of states where abortion is illegal get coverage in other states or help with travel costs?

In recent weeks, many large employers – including Microsoft, Bank of America, Disney, and Netflix – have said they will set up programs to help pay travel costs so workers or other beneficiaries in states with bans can travel to get an abortion elsewhere.

But it isn’t as straightforward as it sounds. Employers will have to figure out whether workers will access this benefit through the health plan or some other reimbursement method. Protecting privacy, too, may be an issue. Some consultants also said employers will need to consider whether their travel reimbursement benefit conflicts with other rules. If an employer, for example, covers travel for abortion procedures but not for an eating disorder clinic, does that violate the Mental Health Parity and Addiction Equity Act? If a plan has no providers willing or able to do abortions, does it violate any state or federal network adequacy rules?

Lawmakers need to think about these conflicts, said Jessica Waltman, vice president for compliance at employee benefits company MZQ Consulting. “They could be putting all the employer group plans in their state in a very precarious position if that state law would prohibit them from complying with federal law,” particularly if they restrict access to benefits called for in the Pregnancy Discrimination Act.

There are other potential conflicts if an employer is in a state that allows abortion but a worker is in a state that restricts it. “If I’m an Oregon-based company, my insurance plan must provide for abortion coverage, but what do I do about an Oklahoma employee? I don’t know the answer,” said René Thorne, a principal at Jackson Lewis, where she oversees litigation that involves self-insured firms.

Also uncertain is whether state laws will take aim at insurers, employers, or others that offer benefits, including travel or televisits, for abortion services.

Laws that restrict abortion, Ms. Thorne wrote in a white paper for clients, generally apply to the medical provider and sometimes those who “aid or abet” the abortion. Some states, including Texas, allow private citizens to sue for $10,000 anyone who provides an illegal abortion or helps a person access an abortion.

Whether those laws will be applied to employers or insurers will undoubtedly end up in the courts.

“We are in uncharted territory here, as we’ve never before been in a situation where plans, as well as their employer sponsors and those administering the plans, might face criminal liability in connection with a plan benefit,” said Seth Perretta, a principal at the Groom Law Group, which advises employers.

Answers won’t come soon, but “there will be so much litigation around this,” said Ms. Thorne.

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

Will your health plan pay for an abortion now that the Supreme Court has overturned Roe v. Wade?

Even before the June 24 ruling, insurance coverage for abortion varied widely. Now the issue is even more complex as states set varying rules – about half are expected to limit or ban abortion in almost all circumstances.

To be clear, though, the question of whether an insurance plan covers abortion is not the same as whether abortion is allowed in a state. Coverage issues are more complicated and governed by a wide variety of factors, including the level of abortion access a state allows.

How dense a thicket is it? Abortion may be covered by a health plan, but if no providers are available, patients don’t have access. However, people with insurance that does not cover abortion can still get one – but only if it’s available in their states or they can afford to travel and pay out of pocket. There are also a host of unanswered questions about whether states that restrict abortion will have the legal authority to target abortion coverage in employer plans.

The issues will likely be before the courts for years to come.

“States will pass laws, there will be some conflict, and then it goes to the courts,” said Erin Fuse Brown, director of the Center for Law, Health & Society at the Georgia State University, Atlanta. “It could be a while.”

In the meantime, here are answers to three common questions.
 

Are health plans – or employers – required to offer coverage for elective abortions?

The simple answer is “no.”

“There’s no law that requires any health plan, employer-based or anything else, to cover an elective abortion,” Ms. Fuse Brown said.

Whether they do is more complicated.

Some job-based health plans cover elective abortions. Patients can search their plan documents or call their insurers directly to check.

Coverage is more likely in plans offered by self-insured employers because a federal pensions law generally preempts state regulation of those health plans. Self-funded employers, which tend to be the larger ones, pay the medical bills, although they generally hire third parties, sometimes health insurers, to handle claims and administrative work.

Still, millions of Americans work for smaller employers, which tend to buy plans directly from health insurers, which then pay the medical bills. Those plans, known as “fully insured,” are subject to state laws, whose approaches to abortion coverage have long varied.

Eleven states bar those private plans from covering abortion in most circumstances, according to KFF, although some of the states allow consumers to purchase an insurance rider that would cover abortion costs.

If you’re not sure what type of health plan you have, ask the administrators.

“There is no way to tell from the face of your insurance card if you are fully insured or self-funded,” Ms. Fuse Brown said.

For the more than 14 million Americans who buy their coverage through the Affordable Care Act marketplaces, their state of residence is key.

Twenty-six states restrict abortion coverage in ACA plans, while seven states require it as a plan benefit, according to KFF. Those states are California, Illinois, Maine, Maryland, New York, Oregon, and Washington.

The rules for Medicaid, the federal-state health program for people with low incomes, also vary. Thirty-four states and the District of Columbia follow the so-called Hyde Amendment, which bars federal funds from paying for abortions, except in cases of rape or incest or to save the life of the mother, although some states allow coverage for other medically necessary abortions.

For all those reasons, it’s not surprising that research published in the journal Health Affairs noted that patients paid out-of-pocket for the majority of abortions (69% in one study). The researchers found that the median cost of a medication abortion was $560 and that abortion procedures ranged from a median of $575 in the first trimester to $895 in the second.
 

What about coverage for pregnancy-related complications that require treatment similar to abortion?

Insurance policies must cover care for essential health services, including medically necessary pregnancy care and abortion when carrying a pregnancy to term would endanger a patient’s life.

Under the Pregnancy Discrimination Act of 1978 and other rules, Ms. Fuse Brown said, “pregnancy and prenatal care, including high-risk pregnancies, and obstetric care in general is required to be covered.”

In an ectopic pregnancy – when a fertilized egg implants outside the uterus – the embryo is not viable, and the condition is generally life-threatening to the mother without medical treatment. Many other scenarios could come into play, including situations in which a woman has a miscarriage but not all the tissue is expelled, potentially leading to a dangerous infection.

Although all state laws that currently restrict abortion include an exception to save the life of the mother, what constitutes a life-threatening scenario is not always clear. That means physicians in abortion-ban states may have to weigh the pregnant person’s medical risk against possible legal ramifications.

“This is less of a coverage question and more of a question of whether providers in the states that ban abortion are going to provide the care,” said Katie Keith, a research faculty member at the Center on Health Insurance Reforms at Georgetown University, Washington. “All of these laws are designed to chill behavior, to make it so unattractive or scary to providers to keep them from doing it at all.”
 

Can residents of states where abortion is illegal get coverage in other states or help with travel costs?

In recent weeks, many large employers – including Microsoft, Bank of America, Disney, and Netflix – have said they will set up programs to help pay travel costs so workers or other beneficiaries in states with bans can travel to get an abortion elsewhere.

But it isn’t as straightforward as it sounds. Employers will have to figure out whether workers will access this benefit through the health plan or some other reimbursement method. Protecting privacy, too, may be an issue. Some consultants also said employers will need to consider whether their travel reimbursement benefit conflicts with other rules. If an employer, for example, covers travel for abortion procedures but not for an eating disorder clinic, does that violate the Mental Health Parity and Addiction Equity Act? If a plan has no providers willing or able to do abortions, does it violate any state or federal network adequacy rules?

Lawmakers need to think about these conflicts, said Jessica Waltman, vice president for compliance at employee benefits company MZQ Consulting. “They could be putting all the employer group plans in their state in a very precarious position if that state law would prohibit them from complying with federal law,” particularly if they restrict access to benefits called for in the Pregnancy Discrimination Act.

There are other potential conflicts if an employer is in a state that allows abortion but a worker is in a state that restricts it. “If I’m an Oregon-based company, my insurance plan must provide for abortion coverage, but what do I do about an Oklahoma employee? I don’t know the answer,” said René Thorne, a principal at Jackson Lewis, where she oversees litigation that involves self-insured firms.

Also uncertain is whether state laws will take aim at insurers, employers, or others that offer benefits, including travel or televisits, for abortion services.

Laws that restrict abortion, Ms. Thorne wrote in a white paper for clients, generally apply to the medical provider and sometimes those who “aid or abet” the abortion. Some states, including Texas, allow private citizens to sue for $10,000 anyone who provides an illegal abortion or helps a person access an abortion.

Whether those laws will be applied to employers or insurers will undoubtedly end up in the courts.

“We are in uncharted territory here, as we’ve never before been in a situation where plans, as well as their employer sponsors and those administering the plans, might face criminal liability in connection with a plan benefit,” said Seth Perretta, a principal at the Groom Law Group, which advises employers.

Answers won’t come soon, but “there will be so much litigation around this,” said Ms. Thorne.

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

The Biden administration issued guidance on July 13 to remind the nation’s 60,000 retail pharmacies of their obligation under federal law to supply prescribed medications, including drugs that may cause an abortion.

The Department of Health & Human Services listed several conditions that are commonly treated with drugs that can induce abortion, warning that withholding the pills could violate civil rights laws and could be considered discrimination based on sex or disability.

“We are committed to ensuring that everyone can access health care, free of discrimination,” Xavier Becerra, the U.S. health and human services secretary, said in a statement. “This includes access to prescription medications for reproductive health and other types of care.”

On July 11, Mr. Becerra issued other guidance to remind hospitals that federal law requires doctors to provide stabilizing treatment for patients with emergency medical conditions, which could include an abortion for those who arrive at emergency departments with a life-threatening issue.

Both actions by the Biden administration assert that federal laws override state laws that have banned or restricted abortion access since the Supreme Court overturned Roe v. Wade, according to The New York Times.

The guidance focuses on Section 1557 of the Affordable Care Act and related federal regulations, which state that recipients of federal financial assistance – including pharmacies that get Medicare and Medicaid payments – can’t discriminate based on race, color, national origin, sex, age, and disability. The guidance highlights that pregnancy discrimination includes discrimination based on current pregnancy, past pregnancy, potential or intended pregnancy, and medical conditions related to pregnancy or childbirth.

Three drugs in particular – mifepristone, misoprostol, and methotrexate – are often prescribed for other medical conditions but can also induce abortions in certain cases. Methotrexate, for example, is used for cancer and autoimmune disorders, such as rheumatoid arthritis.

Mifepristone is often used for patients with Cushing’s syndrome, while misoprostol is often prescribed for ulcers. When used in combination, the two drugs are authorized by the Food and Drug Administration to terminate a pregnancy during the first 10 weeks and after a miscarriage.

Since Roe was overturned, women have posted on social media that they were denied the drugs for their medical conditions due to being of “childbearing age.”

“These are very legitimate issues in terms of people being concerned about having access to the basic medications that they have been receiving for years, just because those medications have the capacity to end a pregnancy,” Alina Salganicoff, PhD, the director of women’s health policy at the Kaiser Family Foundation, told the Times.

“It doesn’t sound like [pharmacies] are blocking this for men,” she said.

The Biden administration’s guidance will likely be challenged in court, the newspaper reported. The update is cautiously written and doesn’t directly say that pharmacies must provide the drugs for the purpose of medication abortion.

In the meantime, pharmacists could feel stuck in the middle. Pharmacists who “believe they are acting in good faith in accordance with their state’s laws on abortion shouldn’t be left without a clear pathway forward,” the National Community Pharmacists Association said in a statement on July 13.

The association, which represents about 19,400 independent pharmacies across the United States, said pharmacies are regulated by states, and most states haven’t advised pharmacists on how to dispense the drugs in question.

“States have provided very little clarity on how pharmacists should proceed in light of conflicting state and federal laws and regulations,” B. Douglas Hoey, the association’s CEO, said in the statement.

“It is highly unfair for state and federal governments to threaten aggressive action against pharmacists who are just trying to serve their patients within new legal boundaries that are still taking shape,” he said.

A version of this article first appeared on WebMD.com.

The Biden administration issued guidance on July 13 to remind the nation’s 60,000 retail pharmacies of their obligation under federal law to supply prescribed medications, including drugs that may cause an abortion.

The Department of Health & Human Services listed several conditions that are commonly treated with drugs that can induce abortion, warning that withholding the pills could violate civil rights laws and could be considered discrimination based on sex or disability.

“We are committed to ensuring that everyone can access health care, free of discrimination,” Xavier Becerra, the U.S. health and human services secretary, said in a statement. “This includes access to prescription medications for reproductive health and other types of care.”

On July 11, Mr. Becerra issued other guidance to remind hospitals that federal law requires doctors to provide stabilizing treatment for patients with emergency medical conditions, which could include an abortion for those who arrive at emergency departments with a life-threatening issue.

Both actions by the Biden administration assert that federal laws override state laws that have banned or restricted abortion access since the Supreme Court overturned Roe v. Wade, according to The New York Times.

The guidance focuses on Section 1557 of the Affordable Care Act and related federal regulations, which state that recipients of federal financial assistance – including pharmacies that get Medicare and Medicaid payments – can’t discriminate based on race, color, national origin, sex, age, and disability. The guidance highlights that pregnancy discrimination includes discrimination based on current pregnancy, past pregnancy, potential or intended pregnancy, and medical conditions related to pregnancy or childbirth.

Three drugs in particular – mifepristone, misoprostol, and methotrexate – are often prescribed for other medical conditions but can also induce abortions in certain cases. Methotrexate, for example, is used for cancer and autoimmune disorders, such as rheumatoid arthritis.

Mifepristone is often used for patients with Cushing’s syndrome, while misoprostol is often prescribed for ulcers. When used in combination, the two drugs are authorized by the Food and Drug Administration to terminate a pregnancy during the first 10 weeks and after a miscarriage.

Since Roe was overturned, women have posted on social media that they were denied the drugs for their medical conditions due to being of “childbearing age.”

“These are very legitimate issues in terms of people being concerned about having access to the basic medications that they have been receiving for years, just because those medications have the capacity to end a pregnancy,” Alina Salganicoff, PhD, the director of women’s health policy at the Kaiser Family Foundation, told the Times.

“It doesn’t sound like [pharmacies] are blocking this for men,” she said.

The Biden administration’s guidance will likely be challenged in court, the newspaper reported. The update is cautiously written and doesn’t directly say that pharmacies must provide the drugs for the purpose of medication abortion.

In the meantime, pharmacists could feel stuck in the middle. Pharmacists who “believe they are acting in good faith in accordance with their state’s laws on abortion shouldn’t be left without a clear pathway forward,” the National Community Pharmacists Association said in a statement on July 13.

The association, which represents about 19,400 independent pharmacies across the United States, said pharmacies are regulated by states, and most states haven’t advised pharmacists on how to dispense the drugs in question.

“States have provided very little clarity on how pharmacists should proceed in light of conflicting state and federal laws and regulations,” B. Douglas Hoey, the association’s CEO, said in the statement.

“It is highly unfair for state and federal governments to threaten aggressive action against pharmacists who are just trying to serve their patients within new legal boundaries that are still taking shape,” he said.

A version of this article first appeared on WebMD.com.

The Biden administration issued guidance on July 13 to remind the nation’s 60,000 retail pharmacies of their obligation under federal law to supply prescribed medications, including drugs that may cause an abortion.

The Department of Health & Human Services listed several conditions that are commonly treated with drugs that can induce abortion, warning that withholding the pills could violate civil rights laws and could be considered discrimination based on sex or disability.

“We are committed to ensuring that everyone can access health care, free of discrimination,” Xavier Becerra, the U.S. health and human services secretary, said in a statement. “This includes access to prescription medications for reproductive health and other types of care.”

On July 11, Mr. Becerra issued other guidance to remind hospitals that federal law requires doctors to provide stabilizing treatment for patients with emergency medical conditions, which could include an abortion for those who arrive at emergency departments with a life-threatening issue.

Both actions by the Biden administration assert that federal laws override state laws that have banned or restricted abortion access since the Supreme Court overturned Roe v. Wade, according to The New York Times.

The guidance focuses on Section 1557 of the Affordable Care Act and related federal regulations, which state that recipients of federal financial assistance – including pharmacies that get Medicare and Medicaid payments – can’t discriminate based on race, color, national origin, sex, age, and disability. The guidance highlights that pregnancy discrimination includes discrimination based on current pregnancy, past pregnancy, potential or intended pregnancy, and medical conditions related to pregnancy or childbirth.

Three drugs in particular – mifepristone, misoprostol, and methotrexate – are often prescribed for other medical conditions but can also induce abortions in certain cases. Methotrexate, for example, is used for cancer and autoimmune disorders, such as rheumatoid arthritis.

Mifepristone is often used for patients with Cushing’s syndrome, while misoprostol is often prescribed for ulcers. When used in combination, the two drugs are authorized by the Food and Drug Administration to terminate a pregnancy during the first 10 weeks and after a miscarriage.

Since Roe was overturned, women have posted on social media that they were denied the drugs for their medical conditions due to being of “childbearing age.”

“These are very legitimate issues in terms of people being concerned about having access to the basic medications that they have been receiving for years, just because those medications have the capacity to end a pregnancy,” Alina Salganicoff, PhD, the director of women’s health policy at the Kaiser Family Foundation, told the Times.

“It doesn’t sound like [pharmacies] are blocking this for men,” she said.

The Biden administration’s guidance will likely be challenged in court, the newspaper reported. The update is cautiously written and doesn’t directly say that pharmacies must provide the drugs for the purpose of medication abortion.

In the meantime, pharmacists could feel stuck in the middle. Pharmacists who “believe they are acting in good faith in accordance with their state’s laws on abortion shouldn’t be left without a clear pathway forward,” the National Community Pharmacists Association said in a statement on July 13.

The association, which represents about 19,400 independent pharmacies across the United States, said pharmacies are regulated by states, and most states haven’t advised pharmacists on how to dispense the drugs in question.

“States have provided very little clarity on how pharmacists should proceed in light of conflicting state and federal laws and regulations,” B. Douglas Hoey, the association’s CEO, said in the statement.

“It is highly unfair for state and federal governments to threaten aggressive action against pharmacists who are just trying to serve their patients within new legal boundaries that are still taking shape,” he said.

A version of this article first appeared on WebMD.com.

Tita AT, Szychowski JM, Boggess K, et al. Treatment for mild chronic hypertension during pregnancy. N Engl J Med. 2022;386:1781-1792. doi: 10.1056/NEJMoa2201295.

Expert Commentary

In the nonpregnant population, medical management of hypertension >140/90 mm Hg is standard practice. By contrast, much higher blood pressures (BPs; up to 160/110 mm Hg) traditionally have been tolerated in pregnant patients with chronic hypertension without initiating treatment, and existing medications are often discontinued during pregnancy. Concern for impaired fetal growth as well as lack of data on improved outcomes have led to different recommendations for the management of mild chronic hypertension in pregnancy. However, chronic hypertension affects a substantial number of pregnant patients and is known to be a risk factor for severe short-term pregnancy and long-term health complications. With preliminary data suggesting that BPs >140/90 mm Hg prior to 20 weeks’ gestation are associated with an increase in adverse outcomes, Tita and colleagues sought to determine the effects of decreasing BP in pregnant patients with mild chronic hypertension.

Details about the study

This is an investigator-initiated, multicenter, pragmatic, open-label, randomized control trial of 2,408 patients with mild chronic hypertension. The active treatment group was treated with antihypertensive medication (including titration of existing medication), targeting a BP of <140/90 mm Hg. The control group only received medication for severe hypertension (≥160 mm Hg systolic or ≥105 mm Hg diastolic). The primary outcome of the study was a composite of preeclampsia with severe features, medically indicated preterm delivery prior to 35 weeks’ gestation (not spontaneous labor or rupture of membranes), placental abruption, and fetal or neonatal death. Birthweight that was less than the 10th percentile was used as a safety outcome. The hypothesis was that treatment would decrease the rate of adverse pregnancy and fetal/neonatal outcomes.

The patient population of singleton pregnancies at a gestational age of less than 23 weeks included 56% with known chronic hypertension on medications, 22% with known chronic hypertension without medications, and 22% with newly diagnosed (during pregnancy) chronic hypertension. The treatment group primarily received labetalol (61.7%) or nifedipine (35.6%); the maximum dose of a single agent was used as tolerated prior to adding a second agent. The control group only received an antihypertensive medication for severe hypertension.

Treatment of chronic hypertension demonstrated a decreased risk of the composite adverse outcome with an adjusted risk ratio of 0.82 (95% confidence interval [CI], 0.74 to 0.92; P<.001) and a number needed to treat (NNT) of 14.7. When analyzed separately, a similar risk reduction was noted for both preeclampsia with severe features and medically indicated preterm birth <35 weeks’ gestation. There was no statistical difference between the groups for birth weight <10th percentile and <5th percentile (adjusted risk ratio, 1.04 [0.82–1.31] vs 0.89 [0.62–1.26], respectively).

Planned subgroup analysis by type of chronic hypertension, race/ethnic group, diabetes status, gestational age at baseline, and body mass index (BMI) demonstrated a similar treatment effect to the overall composite primary outcome, with the exception of patients with newly diagnosed chronic hypertension or BMI ≥40 kg/m². Overall maternal and neonatal composite outcomes of severe complications did not differ between treatment and control groups; however, rates of severe preeclampsia, any preeclampsia, preterm birth rate, and birthweight <2,500 g were all lower in the treatment group.

Study strengths and weaknesses

The study strengths cited are a large sample size, multiple study sites, an independent data and safety monitoring board with close oversight, and centralized blinded confirmation of outcomes. Another strength is that the patient population of the study was similar to the overall population of pregnant patients in the United States with chronic hypertension in terms of age, race, and ethnicity.

The weaknesses of the study include the open-label design and the high ratio of screened to enrolled patients. Both of these issues appear related to the study design (ethics and logistics of a blinded treatment and gestational age cutoff) and the physiology of pregnancy (expected decrease in BP in the second trimester rendering patients ineligible due to lower BP). The study was also not powered to assess treatment effect in all of the subgroups, and further evaluation of patients with newly diagnosed chronic hypertension and BMI ≥ 40 kg/m² is needed. ●

Tita AT, Szychowski JM, Boggess K, et al. Treatment for mild chronic hypertension during pregnancy. N Engl J Med. 2022;386:1781-1792. doi: 10.1056/NEJMoa2201295.

Expert Commentary

In the nonpregnant population, medical management of hypertension >140/90 mm Hg is standard practice. By contrast, much higher blood pressures (BPs; up to 160/110 mm Hg) traditionally have been tolerated in pregnant patients with chronic hypertension without initiating treatment, and existing medications are often discontinued during pregnancy. Concern for impaired fetal growth as well as lack of data on improved outcomes have led to different recommendations for the management of mild chronic hypertension in pregnancy. However, chronic hypertension affects a substantial number of pregnant patients and is known to be a risk factor for severe short-term pregnancy and long-term health complications. With preliminary data suggesting that BPs >140/90 mm Hg prior to 20 weeks’ gestation are associated with an increase in adverse outcomes, Tita and colleagues sought to determine the effects of decreasing BP in pregnant patients with mild chronic hypertension.

Details about the study

This is an investigator-initiated, multicenter, pragmatic, open-label, randomized control trial of 2,408 patients with mild chronic hypertension. The active treatment group was treated with antihypertensive medication (including titration of existing medication), targeting a BP of <140/90 mm Hg. The control group only received medication for severe hypertension (≥160 mm Hg systolic or ≥105 mm Hg diastolic). The primary outcome of the study was a composite of preeclampsia with severe features, medically indicated preterm delivery prior to 35 weeks’ gestation (not spontaneous labor or rupture of membranes), placental abruption, and fetal or neonatal death. Birthweight that was less than the 10th percentile was used as a safety outcome. The hypothesis was that treatment would decrease the rate of adverse pregnancy and fetal/neonatal outcomes.

The patient population of singleton pregnancies at a gestational age of less than 23 weeks included 56% with known chronic hypertension on medications, 22% with known chronic hypertension without medications, and 22% with newly diagnosed (during pregnancy) chronic hypertension. The treatment group primarily received labetalol (61.7%) or nifedipine (35.6%); the maximum dose of a single agent was used as tolerated prior to adding a second agent. The control group only received an antihypertensive medication for severe hypertension.

Treatment of chronic hypertension demonstrated a decreased risk of the composite adverse outcome with an adjusted risk ratio of 0.82 (95% confidence interval [CI], 0.74 to 0.92; P<.001) and a number needed to treat (NNT) of 14.7. When analyzed separately, a similar risk reduction was noted for both preeclampsia with severe features and medically indicated preterm birth <35 weeks’ gestation. There was no statistical difference between the groups for birth weight <10th percentile and <5th percentile (adjusted risk ratio, 1.04 [0.82–1.31] vs 0.89 [0.62–1.26], respectively).

Planned subgroup analysis by type of chronic hypertension, race/ethnic group, diabetes status, gestational age at baseline, and body mass index (BMI) demonstrated a similar treatment effect to the overall composite primary outcome, with the exception of patients with newly diagnosed chronic hypertension or BMI ≥40 kg/m². Overall maternal and neonatal composite outcomes of severe complications did not differ between treatment and control groups; however, rates of severe preeclampsia, any preeclampsia, preterm birth rate, and birthweight <2,500 g were all lower in the treatment group.

Study strengths and weaknesses

The study strengths cited are a large sample size, multiple study sites, an independent data and safety monitoring board with close oversight, and centralized blinded confirmation of outcomes. Another strength is that the patient population of the study was similar to the overall population of pregnant patients in the United States with chronic hypertension in terms of age, race, and ethnicity.

The weaknesses of the study include the open-label design and the high ratio of screened to enrolled patients. Both of these issues appear related to the study design (ethics and logistics of a blinded treatment and gestational age cutoff) and the physiology of pregnancy (expected decrease in BP in the second trimester rendering patients ineligible due to lower BP). The study was also not powered to assess treatment effect in all of the subgroups, and further evaluation of patients with newly diagnosed chronic hypertension and BMI ≥ 40 kg/m² is needed. ●

Tita AT, Szychowski JM, Boggess K, et al. Treatment for mild chronic hypertension during pregnancy. N Engl J Med. 2022;386:1781-1792. doi: 10.1056/NEJMoa2201295.

Expert Commentary

In the nonpregnant population, medical management of hypertension >140/90 mm Hg is standard practice. By contrast, much higher blood pressures (BPs; up to 160/110 mm Hg) traditionally have been tolerated in pregnant patients with chronic hypertension without initiating treatment, and existing medications are often discontinued during pregnancy. Concern for impaired fetal growth as well as lack of data on improved outcomes have led to different recommendations for the management of mild chronic hypertension in pregnancy. However, chronic hypertension affects a substantial number of pregnant patients and is known to be a risk factor for severe short-term pregnancy and long-term health complications. With preliminary data suggesting that BPs >140/90 mm Hg prior to 20 weeks’ gestation are associated with an increase in adverse outcomes, Tita and colleagues sought to determine the effects of decreasing BP in pregnant patients with mild chronic hypertension.

Details about the study

This is an investigator-initiated, multicenter, pragmatic, open-label, randomized control trial of 2,408 patients with mild chronic hypertension. The active treatment group was treated with antihypertensive medication (including titration of existing medication), targeting a BP of <140/90 mm Hg. The control group only received medication for severe hypertension (≥160 mm Hg systolic or ≥105 mm Hg diastolic). The primary outcome of the study was a composite of preeclampsia with severe features, medically indicated preterm delivery prior to 35 weeks’ gestation (not spontaneous labor or rupture of membranes), placental abruption, and fetal or neonatal death. Birthweight that was less than the 10th percentile was used as a safety outcome. The hypothesis was that treatment would decrease the rate of adverse pregnancy and fetal/neonatal outcomes.

The patient population of singleton pregnancies at a gestational age of less than 23 weeks included 56% with known chronic hypertension on medications, 22% with known chronic hypertension without medications, and 22% with newly diagnosed (during pregnancy) chronic hypertension. The treatment group primarily received labetalol (61.7%) or nifedipine (35.6%); the maximum dose of a single agent was used as tolerated prior to adding a second agent. The control group only received an antihypertensive medication for severe hypertension.

Treatment of chronic hypertension demonstrated a decreased risk of the composite adverse outcome with an adjusted risk ratio of 0.82 (95% confidence interval [CI], 0.74 to 0.92; P<.001) and a number needed to treat (NNT) of 14.7. When analyzed separately, a similar risk reduction was noted for both preeclampsia with severe features and medically indicated preterm birth <35 weeks’ gestation. There was no statistical difference between the groups for birth weight <10th percentile and <5th percentile (adjusted risk ratio, 1.04 [0.82–1.31] vs 0.89 [0.62–1.26], respectively).

Planned subgroup analysis by type of chronic hypertension, race/ethnic group, diabetes status, gestational age at baseline, and body mass index (BMI) demonstrated a similar treatment effect to the overall composite primary outcome, with the exception of patients with newly diagnosed chronic hypertension or BMI ≥40 kg/m². Overall maternal and neonatal composite outcomes of severe complications did not differ between treatment and control groups; however, rates of severe preeclampsia, any preeclampsia, preterm birth rate, and birthweight <2,500 g were all lower in the treatment group.

Study strengths and weaknesses

The study strengths cited are a large sample size, multiple study sites, an independent data and safety monitoring board with close oversight, and centralized blinded confirmation of outcomes. Another strength is that the patient population of the study was similar to the overall population of pregnant patients in the United States with chronic hypertension in terms of age, race, and ethnicity.

The weaknesses of the study include the open-label design and the high ratio of screened to enrolled patients. Both of these issues appear related to the study design (ethics and logistics of a blinded treatment and gestational age cutoff) and the physiology of pregnancy (expected decrease in BP in the second trimester rendering patients ineligible due to lower BP). The study was also not powered to assess treatment effect in all of the subgroups, and further evaluation of patients with newly diagnosed chronic hypertension and BMI ≥ 40 kg/m² is needed. ●

Oxytocin and prostaglandins are critically important regulators of uterine contraction. Obstetrician-gynecologists commonly prescribe oxytocin and prostaglandin agonists (misoprostol, dinoprostone) to stimulate uterine contraction for the induction of labor, prevention and treatment of postpartum hemorrhage, and treatment of miscarriage and fetal demise. The focus of this editorial is the clinical pharmacology of misoprostol.

Misoprostol is approved by the US Food and Drug Administration (FDA) for the prevention and treatment of nonsteroidal anti-inflammatory drug–induced gastric ulcers and for patients at high risk for gastric ulcers, including those with a history of gastric ulcers. The approved misoprostol route and dose for this indication is oral administration of 200 µg four times daily with food.¹ Recent food intake and antacid use reduces the absorption of orally administered misoprostol. There are no FDA-approved indications for the use of misoprostol as a single agent in obstetrics and gynecology. The FDA has approved the combination of mifepristone and misoprostol for medication abortion in the first trimester. In contrast to misoprostol, PGE2 (dinoprostone) is approved by the FDA as a vaginal insert containing 10 mg of dinoprostone for the initiation and/or continuation of cervical ripening in patients at or near term in whom there is a medical or obstetric indication for induction of labor (Cervidil; Ferring Pharmaceuticals Inc, Parsippany, New Jersey).²

Pharmacology of misoprostol

Misoprostol is a prostaglandin E1 (PGE1) agonist analogue. Prostaglandin E1 (alprostadil) is rapidly metabolized, has a half-life in the range of minutes and is not orally active, requiring administration by intravenous infusion or injection. It is indicated to maintain a patent ductus arteriosus in newborns with ductal-dependent circulation and to treat erectile dysfunction.³ In contrast to PGE1, misoprostol has a methyl ester group at carbon-1 (C-1) that increases potency and duration of action. Misoprostol also has no hydroxyl group at C-15, replacing that moiety with the addition of both a methyl- and hydroxyl- group at C-16 (FIGURE). These molecular changes improve oral activity and increase duration of action.⁴ Pure misoprostol is a viscous oil. It is formulated into tables by dispersing the oil on hydroxypropyl methyl cellulose before compounding into tablets. Unlike naturally occurring prostaglandins (PGE1), misoprostol tablets are stabile at room temperature for years.⁴

Following absorption, the methyl ester at C-1 is enzymatically cleaved, yielding misoprostol acid, the active drug.⁴ Misoprostol binds to the E prostanoid receptor 3 (EP-3).⁵ Activation of myometrial EP-3 receptor induces an increase in intracellular phosphoinositol turnover and calcium mobilization, resulting in an increase in intracellular-free calcium, triggering actin-myosin contractility.⁶ The increase in free calcium is propagated cell-to-cell through gap junctions that link the myometrial cells to facilitate the generation of a coordinated contraction.

Misoprostol: Various routes of administration are not equal

Misoprostol can be given by an oral, buccal, vaginal, or rectal route of administration. To study the effect of the route of administration on uterine tone and contractility, investigators randomly assigned patients at 8 to 11 weeks’ gestation to receive misoprostol 400 µg as a single dose by the oral or vaginal route. Uterine tone and contractility were measured using an intrauterine pressure transducer. Compared to vaginal administration, oral administration of misprostol was associated with rapid attainment of peak plasma level at 30 minutes, followed by a decline in concentration by 60 minutes. This rapid onset and rapid offset of plasma concentration was paralleled by the onset of uterine tone within 8 minutes, but surprisingly no sustained uterine contractions.⁷ By contrast, following vaginal administration of misoprostol, serum levels rose slowly and peaked in 1 to 2 hours. Uterine tone increased within 21 minutes, and sustained uterine contractions were recorded for 4 hours.⁷ The rapid rise and fall in plasma misoprostol following oral administration and the more sustained plasma misoprostol concentration over 4 hours has been previously reported.⁸ In a second study involving patients 8 to 11 weeks’ gestation, the effect of a single dose of misoprostol 400 µg by an oral or vaginal route on uterine contractility was compared using an intrauterine pressure transducer.⁹ Confirming previous results, the time from misoprostol administration to increased uterine tone was more rapid with oral than with vaginal administration (8 min vs 19 min). Over the course of 4 hours, uterine contraction activity was greater with vaginal than with oral administration (454 vs 166 Montevideo units).⁹

Both studies reported that oral administration of misoprostol resulted in more rapid onset and offset of action than vaginal administration. Oral administration of a single dose of misoprostol 400 µg did not result in sustained uterine contractions in most patients in the first trimester. Vaginal administration produced a slower onset of increased uterine tone but sustained uterine contractions over 4 hours. Compared with vaginal administration of misoprostol, the rapid onset and offset of action of oral misoprostol may reduce the rate of tachysystole and changes in fetal heart rate observed with vaginal administration.¹⁰

An important finding is that buccal and vaginal administration of misoprostol have similar effects on uterine tone in the first trimester.¹¹ To study the effect of buccal and vaginal administration of misoprostol on uterine tone, patients 6 to 13 weeks’ gestation were randomly allocated to receive a single dose of misoprostol 400 µg by a buccal or vaginal route.¹¹ Uterine activity over 5 hours following administration was assessed using an intrauterine pressure transducer. Uterine tone 20 to 30 minutes after buccal or vaginal administration of misoprostol (400 µg) was 27 and 28 mm Hg, respectively. Peak uterine tone, as measured by an intrauterine pressure transducer, for buccal and vaginal administration of misoprostol was 49 mm Hg and 54 mm Hg, respectively. Total Alexandria units (AU) over 5 hours following buccal or vaginal administration was 6,537 AU and 6,090 AU, respectively.¹¹

An AU is calculated as the average amplitude of the contractions (mm Hg) multiplied by the average duration of the contractions (min) multiplied by average frequency of contraction over 10 minutes.¹² By contrast, a Montevideo unit does not include an assessment of contraction duration and is calculated as average amplitude of contractions (mm Hg) multiplied by frequency of uterine contractions over 10 minutes.¹²

In contrast to buccal or vaginal administration, rectal administration of misoprostol resulted in much lower peak uterine tone and contractility as measured by a pressure transducer. Uterine tone 20 to 30 minutes after vaginal and rectal administration of misoprostol (400 µg) was 28 and 19 mm Hg, respectively.¹¹ Peak uterine tone, as measured by an intrauterine pressure transducer, for vaginal and rectal administration of misoprostol was 54 and 31 mm Hg, respectively. AUs over 5 hours following vaginal and rectal administration was 6,090 AU and 2,768 AU, respectively.¹¹ Compared with buccal and vaginal administration of misoprostol, rectal administration produced less sustained uterine contractions in the first trimester of pregnancy. To achieve maximal sustained uterine contractions, buccal and vaginal routes of administration are superior to oral and rectal administration.

Continue to: Misoprostol and cervical ripening...

Misoprostol is commonly used to soften and ripen the cervix. Some of the cervical ripening effects of misoprostol are likely due to increased uterine tone. In addition, misoprostol may have a direct effect on the collagen structure of the cervix. To study the effect of misoprostol on the cervix, pregnant patients in the first trimester were randomly assigned to receive misoprostol 200 µg by vaginal self-administration, isosorbide mononitrate (IMN) 40 mg by vaginal self-administration or no treatment the evening prior to pregnancy termination.¹³ The following day, before uterine evacuation, a cervical biopsy was obtained for electron microscopy studies and immunohistochemistry to assess the presence of enzymes involved in collagen degradation, including matrix metalloproteinase 1 (MMP-1) and matrix metalloproteinase 9 (MMP-9). Electron microscopy demonstrated that pretreatment with misoprostol resulted in a pronounced splitting and disorganization of collagen fibers.¹³ Compared with misoprostol treatment, IMN produced less splitting and disorganization of collagen fibers, and in the no treatment group, no marked changes in the collagen framework were observed.

Compared with no treatment, misoprostol and IMN pretreatment were associated with marked increases in MMP-1 and MMP-9 as assessed by immunohistochemistry. Misoprostol pretreatment also resulted in a significant increase in interleukin-8 concentration compared with IMN pretreatment and no treatment (8.8 vs 2.7 vs 2.4 pg/mg tissue), respectively.¹³ Other investigators have also reported that misoprostol increased cervical leukocyte influx and collagen disrupting enzymes MMP-8 and MMP-9.^14,15

An open-label clinical trial compared the efficacy of misoprostol versus Foley catheter for labor induction at term in 1,859 patients ≥ 37 weeks’ gestation with a Bishop score <6.¹⁶ Patients were randomly allocated to misoprostol (50 µg orally every 4 hours up to 3 times in 24 hours) versus placement of a 16 F or 18 F Foley catheter introduced through the cervix, filled with 30 mL of sodium chloride or water. The investigators reported that oral misoprostol and Foley catheter cervical ripening had similar safety and effectiveness for cervical ripening as a prelude to induction of labor, including no statistically significant differences in 5-minute Apgar score <7, umbilical cord artery pH ≤ 7.05, postpartum hemorrhage, or cesarean birth rate.¹⁶

Bottom line

Misoprostol and oxytocin are commonly prescribed in obstetric practice for cervical ripening and induction of labor, respectively. The dose and route of administration of misoprostol influences the effect on the uterus. For cervical ripening, where rapid onset and offset may help to reduce the risk of uterine tachysystole and worrisome fetal heart rate changes, low-dose (50 µg) oral administration of misoprostol may be a preferred dose and route. For the treatment of miscarriage and fetal demise, to stimulate sustained uterine contractions over many hours, buccal and vaginal administration of misoprostol are preferred. Rectal administration is generally inferior to buccal and vaginal administration for stimulating sustained uterine contractions and its uses should be limited. ●

Oxytocin and prostaglandins are critically important regulators of uterine contraction. Obstetrician-gynecologists commonly prescribe oxytocin and prostaglandin agonists (misoprostol, dinoprostone) to stimulate uterine contraction for the induction of labor, prevention and treatment of postpartum hemorrhage, and treatment of miscarriage and fetal demise. The focus of this editorial is the clinical pharmacology of misoprostol.

Misoprostol is approved by the US Food and Drug Administration (FDA) for the prevention and treatment of nonsteroidal anti-inflammatory drug–induced gastric ulcers and for patients at high risk for gastric ulcers, including those with a history of gastric ulcers. The approved misoprostol route and dose for this indication is oral administration of 200 µg four times daily with food.¹ Recent food intake and antacid use reduces the absorption of orally administered misoprostol. There are no FDA-approved indications for the use of misoprostol as a single agent in obstetrics and gynecology. The FDA has approved the combination of mifepristone and misoprostol for medication abortion in the first trimester. In contrast to misoprostol, PGE2 (dinoprostone) is approved by the FDA as a vaginal insert containing 10 mg of dinoprostone for the initiation and/or continuation of cervical ripening in patients at or near term in whom there is a medical or obstetric indication for induction of labor (Cervidil; Ferring Pharmaceuticals Inc, Parsippany, New Jersey).²

Pharmacology of misoprostol

Misoprostol is a prostaglandin E1 (PGE1) agonist analogue. Prostaglandin E1 (alprostadil) is rapidly metabolized, has a half-life in the range of minutes and is not orally active, requiring administration by intravenous infusion or injection. It is indicated to maintain a patent ductus arteriosus in newborns with ductal-dependent circulation and to treat erectile dysfunction.³ In contrast to PGE1, misoprostol has a methyl ester group at carbon-1 (C-1) that increases potency and duration of action. Misoprostol also has no hydroxyl group at C-15, replacing that moiety with the addition of both a methyl- and hydroxyl- group at C-16 (FIGURE). These molecular changes improve oral activity and increase duration of action.⁴ Pure misoprostol is a viscous oil. It is formulated into tables by dispersing the oil on hydroxypropyl methyl cellulose before compounding into tablets. Unlike naturally occurring prostaglandins (PGE1), misoprostol tablets are stabile at room temperature for years.⁴

Following absorption, the methyl ester at C-1 is enzymatically cleaved, yielding misoprostol acid, the active drug.⁴ Misoprostol binds to the E prostanoid receptor 3 (EP-3).⁵ Activation of myometrial EP-3 receptor induces an increase in intracellular phosphoinositol turnover and calcium mobilization, resulting in an increase in intracellular-free calcium, triggering actin-myosin contractility.⁶ The increase in free calcium is propagated cell-to-cell through gap junctions that link the myometrial cells to facilitate the generation of a coordinated contraction.

Misoprostol: Various routes of administration are not equal

Misoprostol can be given by an oral, buccal, vaginal, or rectal route of administration. To study the effect of the route of administration on uterine tone and contractility, investigators randomly assigned patients at 8 to 11 weeks’ gestation to receive misoprostol 400 µg as a single dose by the oral or vaginal route. Uterine tone and contractility were measured using an intrauterine pressure transducer. Compared to vaginal administration, oral administration of misprostol was associated with rapid attainment of peak plasma level at 30 minutes, followed by a decline in concentration by 60 minutes. This rapid onset and rapid offset of plasma concentration was paralleled by the onset of uterine tone within 8 minutes, but surprisingly no sustained uterine contractions.⁷ By contrast, following vaginal administration of misoprostol, serum levels rose slowly and peaked in 1 to 2 hours. Uterine tone increased within 21 minutes, and sustained uterine contractions were recorded for 4 hours.⁷ The rapid rise and fall in plasma misoprostol following oral administration and the more sustained plasma misoprostol concentration over 4 hours has been previously reported.⁸ In a second study involving patients 8 to 11 weeks’ gestation, the effect of a single dose of misoprostol 400 µg by an oral or vaginal route on uterine contractility was compared using an intrauterine pressure transducer.⁹ Confirming previous results, the time from misoprostol administration to increased uterine tone was more rapid with oral than with vaginal administration (8 min vs 19 min). Over the course of 4 hours, uterine contraction activity was greater with vaginal than with oral administration (454 vs 166 Montevideo units).⁹

Both studies reported that oral administration of misoprostol resulted in more rapid onset and offset of action than vaginal administration. Oral administration of a single dose of misoprostol 400 µg did not result in sustained uterine contractions in most patients in the first trimester. Vaginal administration produced a slower onset of increased uterine tone but sustained uterine contractions over 4 hours. Compared with vaginal administration of misoprostol, the rapid onset and offset of action of oral misoprostol may reduce the rate of tachysystole and changes in fetal heart rate observed with vaginal administration.¹⁰

An important finding is that buccal and vaginal administration of misoprostol have similar effects on uterine tone in the first trimester.¹¹ To study the effect of buccal and vaginal administration of misoprostol on uterine tone, patients 6 to 13 weeks’ gestation were randomly allocated to receive a single dose of misoprostol 400 µg by a buccal or vaginal route.¹¹ Uterine activity over 5 hours following administration was assessed using an intrauterine pressure transducer. Uterine tone 20 to 30 minutes after buccal or vaginal administration of misoprostol (400 µg) was 27 and 28 mm Hg, respectively. Peak uterine tone, as measured by an intrauterine pressure transducer, for buccal and vaginal administration of misoprostol was 49 mm Hg and 54 mm Hg, respectively. Total Alexandria units (AU) over 5 hours following buccal or vaginal administration was 6,537 AU and 6,090 AU, respectively.¹¹

An AU is calculated as the average amplitude of the contractions (mm Hg) multiplied by the average duration of the contractions (min) multiplied by average frequency of contraction over 10 minutes.¹² By contrast, a Montevideo unit does not include an assessment of contraction duration and is calculated as average amplitude of contractions (mm Hg) multiplied by frequency of uterine contractions over 10 minutes.¹²

In contrast to buccal or vaginal administration, rectal administration of misoprostol resulted in much lower peak uterine tone and contractility as measured by a pressure transducer. Uterine tone 20 to 30 minutes after vaginal and rectal administration of misoprostol (400 µg) was 28 and 19 mm Hg, respectively.¹¹ Peak uterine tone, as measured by an intrauterine pressure transducer, for vaginal and rectal administration of misoprostol was 54 and 31 mm Hg, respectively. AUs over 5 hours following vaginal and rectal administration was 6,090 AU and 2,768 AU, respectively.¹¹ Compared with buccal and vaginal administration of misoprostol, rectal administration produced less sustained uterine contractions in the first trimester of pregnancy. To achieve maximal sustained uterine contractions, buccal and vaginal routes of administration are superior to oral and rectal administration.

Continue to: Misoprostol and cervical ripening...

Misoprostol is commonly used to soften and ripen the cervix. Some of the cervical ripening effects of misoprostol are likely due to increased uterine tone. In addition, misoprostol may have a direct effect on the collagen structure of the cervix. To study the effect of misoprostol on the cervix, pregnant patients in the first trimester were randomly assigned to receive misoprostol 200 µg by vaginal self-administration, isosorbide mononitrate (IMN) 40 mg by vaginal self-administration or no treatment the evening prior to pregnancy termination.¹³ The following day, before uterine evacuation, a cervical biopsy was obtained for electron microscopy studies and immunohistochemistry to assess the presence of enzymes involved in collagen degradation, including matrix metalloproteinase 1 (MMP-1) and matrix metalloproteinase 9 (MMP-9). Electron microscopy demonstrated that pretreatment with misoprostol resulted in a pronounced splitting and disorganization of collagen fibers.¹³ Compared with misoprostol treatment, IMN produced less splitting and disorganization of collagen fibers, and in the no treatment group, no marked changes in the collagen framework were observed.

Compared with no treatment, misoprostol and IMN pretreatment were associated with marked increases in MMP-1 and MMP-9 as assessed by immunohistochemistry. Misoprostol pretreatment also resulted in a significant increase in interleukin-8 concentration compared with IMN pretreatment and no treatment (8.8 vs 2.7 vs 2.4 pg/mg tissue), respectively.¹³ Other investigators have also reported that misoprostol increased cervical leukocyte influx and collagen disrupting enzymes MMP-8 and MMP-9.^14,15

An open-label clinical trial compared the efficacy of misoprostol versus Foley catheter for labor induction at term in 1,859 patients ≥ 37 weeks’ gestation with a Bishop score <6.¹⁶ Patients were randomly allocated to misoprostol (50 µg orally every 4 hours up to 3 times in 24 hours) versus placement of a 16 F or 18 F Foley catheter introduced through the cervix, filled with 30 mL of sodium chloride or water. The investigators reported that oral misoprostol and Foley catheter cervical ripening had similar safety and effectiveness for cervical ripening as a prelude to induction of labor, including no statistically significant differences in 5-minute Apgar score <7, umbilical cord artery pH ≤ 7.05, postpartum hemorrhage, or cesarean birth rate.¹⁶

Bottom line

Misoprostol and oxytocin are commonly prescribed in obstetric practice for cervical ripening and induction of labor, respectively. The dose and route of administration of misoprostol influences the effect on the uterus. For cervical ripening, where rapid onset and offset may help to reduce the risk of uterine tachysystole and worrisome fetal heart rate changes, low-dose (50 µg) oral administration of misoprostol may be a preferred dose and route. For the treatment of miscarriage and fetal demise, to stimulate sustained uterine contractions over many hours, buccal and vaginal administration of misoprostol are preferred. Rectal administration is generally inferior to buccal and vaginal administration for stimulating sustained uterine contractions and its uses should be limited. ●

Oxytocin and prostaglandins are critically important regulators of uterine contraction. Obstetrician-gynecologists commonly prescribe oxytocin and prostaglandin agonists (misoprostol, dinoprostone) to stimulate uterine contraction for the induction of labor, prevention and treatment of postpartum hemorrhage, and treatment of miscarriage and fetal demise. The focus of this editorial is the clinical pharmacology of misoprostol.

Misoprostol is approved by the US Food and Drug Administration (FDA) for the prevention and treatment of nonsteroidal anti-inflammatory drug–induced gastric ulcers and for patients at high risk for gastric ulcers, including those with a history of gastric ulcers. The approved misoprostol route and dose for this indication is oral administration of 200 µg four times daily with food.¹ Recent food intake and antacid use reduces the absorption of orally administered misoprostol. There are no FDA-approved indications for the use of misoprostol as a single agent in obstetrics and gynecology. The FDA has approved the combination of mifepristone and misoprostol for medication abortion in the first trimester. In contrast to misoprostol, PGE2 (dinoprostone) is approved by the FDA as a vaginal insert containing 10 mg of dinoprostone for the initiation and/or continuation of cervical ripening in patients at or near term in whom there is a medical or obstetric indication for induction of labor (Cervidil; Ferring Pharmaceuticals Inc, Parsippany, New Jersey).²

Pharmacology of misoprostol

Misoprostol is a prostaglandin E1 (PGE1) agonist analogue. Prostaglandin E1 (alprostadil) is rapidly metabolized, has a half-life in the range of minutes and is not orally active, requiring administration by intravenous infusion or injection. It is indicated to maintain a patent ductus arteriosus in newborns with ductal-dependent circulation and to treat erectile dysfunction.³ In contrast to PGE1, misoprostol has a methyl ester group at carbon-1 (C-1) that increases potency and duration of action. Misoprostol also has no hydroxyl group at C-15, replacing that moiety with the addition of both a methyl- and hydroxyl- group at C-16 (FIGURE). These molecular changes improve oral activity and increase duration of action.⁴ Pure misoprostol is a viscous oil. It is formulated into tables by dispersing the oil on hydroxypropyl methyl cellulose before compounding into tablets. Unlike naturally occurring prostaglandins (PGE1), misoprostol tablets are stabile at room temperature for years.⁴

Following absorption, the methyl ester at C-1 is enzymatically cleaved, yielding misoprostol acid, the active drug.⁴ Misoprostol binds to the E prostanoid receptor 3 (EP-3).⁵ Activation of myometrial EP-3 receptor induces an increase in intracellular phosphoinositol turnover and calcium mobilization, resulting in an increase in intracellular-free calcium, triggering actin-myosin contractility.⁶ The increase in free calcium is propagated cell-to-cell through gap junctions that link the myometrial cells to facilitate the generation of a coordinated contraction.

Misoprostol: Various routes of administration are not equal

Misoprostol can be given by an oral, buccal, vaginal, or rectal route of administration. To study the effect of the route of administration on uterine tone and contractility, investigators randomly assigned patients at 8 to 11 weeks’ gestation to receive misoprostol 400 µg as a single dose by the oral or vaginal route. Uterine tone and contractility were measured using an intrauterine pressure transducer. Compared to vaginal administration, oral administration of misprostol was associated with rapid attainment of peak plasma level at 30 minutes, followed by a decline in concentration by 60 minutes. This rapid onset and rapid offset of plasma concentration was paralleled by the onset of uterine tone within 8 minutes, but surprisingly no sustained uterine contractions.⁷ By contrast, following vaginal administration of misoprostol, serum levels rose slowly and peaked in 1 to 2 hours. Uterine tone increased within 21 minutes, and sustained uterine contractions were recorded for 4 hours.⁷ The rapid rise and fall in plasma misoprostol following oral administration and the more sustained plasma misoprostol concentration over 4 hours has been previously reported.⁸ In a second study involving patients 8 to 11 weeks’ gestation, the effect of a single dose of misoprostol 400 µg by an oral or vaginal route on uterine contractility was compared using an intrauterine pressure transducer.⁹ Confirming previous results, the time from misoprostol administration to increased uterine tone was more rapid with oral than with vaginal administration (8 min vs 19 min). Over the course of 4 hours, uterine contraction activity was greater with vaginal than with oral administration (454 vs 166 Montevideo units).⁹

Both studies reported that oral administration of misoprostol resulted in more rapid onset and offset of action than vaginal administration. Oral administration of a single dose of misoprostol 400 µg did not result in sustained uterine contractions in most patients in the first trimester. Vaginal administration produced a slower onset of increased uterine tone but sustained uterine contractions over 4 hours. Compared with vaginal administration of misoprostol, the rapid onset and offset of action of oral misoprostol may reduce the rate of tachysystole and changes in fetal heart rate observed with vaginal administration.¹⁰

An important finding is that buccal and vaginal administration of misoprostol have similar effects on uterine tone in the first trimester.¹¹ To study the effect of buccal and vaginal administration of misoprostol on uterine tone, patients 6 to 13 weeks’ gestation were randomly allocated to receive a single dose of misoprostol 400 µg by a buccal or vaginal route.¹¹ Uterine activity over 5 hours following administration was assessed using an intrauterine pressure transducer. Uterine tone 20 to 30 minutes after buccal or vaginal administration of misoprostol (400 µg) was 27 and 28 mm Hg, respectively. Peak uterine tone, as measured by an intrauterine pressure transducer, for buccal and vaginal administration of misoprostol was 49 mm Hg and 54 mm Hg, respectively. Total Alexandria units (AU) over 5 hours following buccal or vaginal administration was 6,537 AU and 6,090 AU, respectively.¹¹

An AU is calculated as the average amplitude of the contractions (mm Hg) multiplied by the average duration of the contractions (min) multiplied by average frequency of contraction over 10 minutes.¹² By contrast, a Montevideo unit does not include an assessment of contraction duration and is calculated as average amplitude of contractions (mm Hg) multiplied by frequency of uterine contractions over 10 minutes.¹²

In contrast to buccal or vaginal administration, rectal administration of misoprostol resulted in much lower peak uterine tone and contractility as measured by a pressure transducer. Uterine tone 20 to 30 minutes after vaginal and rectal administration of misoprostol (400 µg) was 28 and 19 mm Hg, respectively.¹¹ Peak uterine tone, as measured by an intrauterine pressure transducer, for vaginal and rectal administration of misoprostol was 54 and 31 mm Hg, respectively. AUs over 5 hours following vaginal and rectal administration was 6,090 AU and 2,768 AU, respectively.¹¹ Compared with buccal and vaginal administration of misoprostol, rectal administration produced less sustained uterine contractions in the first trimester of pregnancy. To achieve maximal sustained uterine contractions, buccal and vaginal routes of administration are superior to oral and rectal administration.

Continue to: Misoprostol and cervical ripening...

Misoprostol is commonly used to soften and ripen the cervix. Some of the cervical ripening effects of misoprostol are likely due to increased uterine tone. In addition, misoprostol may have a direct effect on the collagen structure of the cervix. To study the effect of misoprostol on the cervix, pregnant patients in the first trimester were randomly assigned to receive misoprostol 200 µg by vaginal self-administration, isosorbide mononitrate (IMN) 40 mg by vaginal self-administration or no treatment the evening prior to pregnancy termination.¹³ The following day, before uterine evacuation, a cervical biopsy was obtained for electron microscopy studies and immunohistochemistry to assess the presence of enzymes involved in collagen degradation, including matrix metalloproteinase 1 (MMP-1) and matrix metalloproteinase 9 (MMP-9). Electron microscopy demonstrated that pretreatment with misoprostol resulted in a pronounced splitting and disorganization of collagen fibers.¹³ Compared with misoprostol treatment, IMN produced less splitting and disorganization of collagen fibers, and in the no treatment group, no marked changes in the collagen framework were observed.

Compared with no treatment, misoprostol and IMN pretreatment were associated with marked increases in MMP-1 and MMP-9 as assessed by immunohistochemistry. Misoprostol pretreatment also resulted in a significant increase in interleukin-8 concentration compared with IMN pretreatment and no treatment (8.8 vs 2.7 vs 2.4 pg/mg tissue), respectively.¹³ Other investigators have also reported that misoprostol increased cervical leukocyte influx and collagen disrupting enzymes MMP-8 and MMP-9.^14,15

An open-label clinical trial compared the efficacy of misoprostol versus Foley catheter for labor induction at term in 1,859 patients ≥ 37 weeks’ gestation with a Bishop score <6.¹⁶ Patients were randomly allocated to misoprostol (50 µg orally every 4 hours up to 3 times in 24 hours) versus placement of a 16 F or 18 F Foley catheter introduced through the cervix, filled with 30 mL of sodium chloride or water. The investigators reported that oral misoprostol and Foley catheter cervical ripening had similar safety and effectiveness for cervical ripening as a prelude to induction of labor, including no statistically significant differences in 5-minute Apgar score <7, umbilical cord artery pH ≤ 7.05, postpartum hemorrhage, or cesarean birth rate.¹⁶

Bottom line

Misoprostol and oxytocin are commonly prescribed in obstetric practice for cervical ripening and induction of labor, respectively. The dose and route of administration of misoprostol influences the effect on the uterus. For cervical ripening, where rapid onset and offset may help to reduce the risk of uterine tachysystole and worrisome fetal heart rate changes, low-dose (50 µg) oral administration of misoprostol may be a preferred dose and route. For the treatment of miscarriage and fetal demise, to stimulate sustained uterine contractions over many hours, buccal and vaginal administration of misoprostol are preferred. Rectal administration is generally inferior to buccal and vaginal administration for stimulating sustained uterine contractions and its uses should be limited. ●

For the infections we most commonly encounter in obstetric practice, I review in this article the selection of specific antibiotics. I focus on the key pathogens that cause these infections, the most useful diagnostic tests, and the most cost-effective antibiotic therapy. Relative cost estimates (high vs low) for drugs are based on information published on the GoodRx website (https://www.goodrx.com/). Actual charges to patients, of course, may vary widely depending on contractual relationships between hospitals, insurance companies, and wholesale vendors. The infections are listed in alphabetical order, not in order of frequency or severity.

1. Bacterial vaginosis

Bacterial vaginosis (BV) is a polymicrobial infection that results from perturbation of the normal vaginal flora due to conditions such as pregnancy, hormonal therapy, and changes in the menstrual cycle. It is characterized by a decrease in the vaginal concentration of Lactobacillus crispatus, followed by an increase in Prevotella bivia, Gardnerella vaginalis, Mobiluncus species, Atopobium vaginae, and Megasphaera type 1.^1,2

BV is characterized by a thin, white-gray malodorous (fishlike smell) discharge. The vaginal pH is >4.5. Clue cells are apparent on saline microscopy, and the whiff (amine) test is positive when potassium hydroxide is added to a drop of vaginal secretions. Diagnostic accuracy can be improved using one of the new vaginal panel assays such as BD MAX Vaginal Panel (Becton, Dickinson and Company).³

Antibiotic selection

Antibiotic treatment of BV is directed primarily at the anaerobic component of the infection. The preferred treatment is oral metronidazole 500 mg twice daily for 7 days. If the patient cannot tolerate metronidazole, oral clindamycin 300 mg twice daily for 7 days, can be used, although it is more expensive than metronidazole. Topical metronidazole vaginal gel (0.75%), 1 applicatorful daily for 5 days, is effective in treating the local vaginal infection, but it is not effective in preventing systemic complications such as preterm labor, chorioamnionitis, and puerperal endometritis.² It also is significantly more expensive than the oral formulation of metronidazole. Topical clindamycin cream, 1 applicatorful daily for 5 days, is even more expensive.

Tinidazole 2 g orally daily for 2 days is an effective alternative to oral metronidazole. Single-dose therapy with oral secnidazole (2 g), a 5-nitroimidazole with a longer half-life than metronidazole, has been effective in small studies, but experience with this drug in the United States is limited. Secnidazole is also very expensive.⁴

2. Candidiasis

Vulvovaginal candidiasis usually is caused by Candida albicans. Other less common species include C tropicalis, C glabrata, C auris, C lusitaniae, and C krusei. The most common clinical findings are vulvovaginal pruritus in association with a curdlike white vaginal discharge. The diagnosis can be established by confirmation of a normal vaginal pH and identification of budding yeast and hyphae on a potassium hydroxide preparation. As noted above for BV, the vaginal panel assay improves the accuracy of clinical diagnosis.³ Culture usually is indicated only in patients with infections that are refractory to therapy.

Continue to: Antibiotic selection...

Antibiotic selection

In the first trimester of pregnancy, vulvovaginal candidiasis should be treated with a topical medication such as clotrimazole cream 1% (50 mg intravaginally daily for 7 days), miconazole cream 2% (100 mg intravaginally daily for 7 days), or terconazole cream 0.4% (50 g intravaginally daily for 7 days). Single-dose formulations or 3-day courses of treatment may not be quite as effective in pregnant patients, but they do offer a more convenient dosing schedule.^2,5

Oral fluconazole should not be used in the first trimester of pregnancy because it has been associated with an increased risk for spontaneous abortion and with fetal cardiac septal defects. Beyond the first trimester, oral fluconazole offers an attractive option for treatment of vulvovaginal candidiasis. The appropriate dose is 150 mg initially, with a repeat dose in 3 days if symptoms persist.^2,5

Ibrexafungerp (300 mg twice daily for 1 day) was recently approved by the US Food and Drug Administration (FDA) for oral treatment of vulvovaginal candidiasis. However, this drug is teratogenic and is contraindicated during pregnancy and lactation. It also is significantly more expensive than fluconazole.⁶

3. Cesarean delivery prophylaxis

All women having a cesarean delivery (CD) should receive antibiotic prophylaxis to reduce the risk of endometritis and wound infection.

Antibiotic selection

In my opinion, the preferred regimen is intravenous cefazolin 2 g plus azithromycin 500 mg administered preoperatively.⁷ Cefazolin can be administered in a rapid bolus; azithromycin should be administered over 1 hour.

In an exceptionally rigorous investigation called the C/SOAP trial (Cesarean Section Optimal Antibiotic Prophylaxis trial), Tita and colleagues showed that the combination of cefazolin plus azithromycin was superior to single-agent prophylaxis (usually with cefazolin) in preventing the composite of endometritis, wound infection, or other infection occurring within 6 weeks of surgery.⁸ The additive effect of azithromycin was particularly pronounced in patients having CD after labor and rupture of membranes. Harper and associates subsequently validated the cost-effectiveness of this combination regimen using a decision analytic model.⁹

If the patient has a serious allergy to β-lactam antibiotics, the best alternative regimen for prophylaxis is clindamycin plus gentamicin. The appropriate single intravenous dose of clindamycin is 900 mg; the single dose of gentamicin should be 5 mg/kg of ideal body weight (IBW).⁷

4. Chlamydia

Chlamydia trachomatis is an obligate intracellular bacterium. In pregnant women, it typically causes urethritis, endocervicitis, and inflammatory proctitis. Along with gonorrhea, it is the cause of an unusual infection/inflammation of the liver capsule, termed Fitz-Hugh-Curtis syndrome (perihepatitis). The diagnosis of chlamydia infection is best confirmed with a nucleic acid amplification test (NAAT). The NAAT simultaneously tests for chlamydia and gonorrhea in urine or in secretions obtained from the urethra, endocervix, and rectum.²

Antibiotic selection

The drug of choice for treating chlamydia in pregnancy is azithromycin 1,000 mg orally in a single dose. Erythromycin can be used as an alternative to azithromycin, but it usually is not well tolerated because of gastrointestinal adverse effects. In my practice, the preferred alternative for a patient who cannot tolerate azithromycin is amoxicillin 500 mg orally 3 times daily for 7 days.^2,10

Continue to: 5. Chorioamnionitis...

5. Chorioamnionitis

Chorioamnionitis is a polymicrobial infection caused by anaerobes, aerobic gram-negative bacilli (predominantly Escherichia coli), and aerobic gram-positive cocci (primarily group B streptococci [GBS]). The diagnosis usually is made based on clinical examination: maternal fever, maternal and fetal tachycardia, and no other localizing sign of infection. The diagnosis can be confirmed by obtaining a sample of amniotic fluid via amniocentesis or via aspiration through the intrauterine pressure catheter and demonstrating a positive Gram stain, low glucose concentration (<20 mg/dL), positive nitrites, positive leukocyte esterase, and ultimately, a positive bacteriologic culture.²

Antibiotic selection

The initial treatment of chorioamnionitis specifically targets the 2 major organisms that cause neonatal pneumonia, meningitis, and sepsis: GBS and E coli. For many years, the drugs of choice have been intravenous ampicillin (2 g every 6 hours) plus intravenous gentamicin (5 mg/kg of IBW every 24 hours). Gentamicin also can be administered intravenously at a dose of 1.5 mg/kg every 8 hours. I prefer the once-daily dosing for 3 reasons:

• Gentamicin works by a concentration-dependent mechanism; the higher the initial serum concentration, the better the killing effect.
• Once-daily dosing preserves long periods with low trough levels, an effect that minimizes ototoxicity and nephrotoxicity.
• Once-daily dosing is more convenient.

In a patient who has a contraindication to use of an aminoglycoside, aztreonam (2 g intravenously every 8 hours) may be combined with ampicillin.²

If the patient delivers vaginally, 1 dose of each drug should be administered postpartum, and then the antibiotics should be discontinued. If the patient delivers by cesarean, a single dose of a medication with strong anaerobic coverage should be administered immediately after the infant’s umbilical cord is clamped. Options include clindamycin (900 mg intravenously) or metronidazole (500 mg intravenously).¹¹

There are 2 key exceptions to the single postpartum dose rule, however. If the patient is obese (body mass index [BMI] >30 kg/m²) or if the membranes have been ruptured for more than 24 hours, antibiotics should be continued until she has been afebrile and asymptomatic for 24 hours.¹²

Two single agents are excellent alternatives to the combination ampicillin-gentamicin regimen. One is ampicillin-sulbactam, 3 g intravenously every 6 hours. The other is piperacillin-tazobactam, 3.375 g intravenously every 6 hours. These extended-spectrum penicillins provide exceptionally good coverage against the major pathogens that cause chorioamnionitis. Although more expensive than the combination regimen, they avoid the potential ototoxicity and nephrotoxicity associated with gentamicin.²

6. Endometritis

Puerperal endometritis is significantly more common after CD than after vaginal delivery. The infection is polymicrobial, and the principal pathogens are anaerobic gram-positive cocci, anaerobic gram-negative bacilli, aerobic gram-negative bacilli, and aerobic gram-positive cocci. The diagnosis usually is made almost exclusively based on clinical findings: fever within 24 to 36 hours of delivery, tachycardia, mild tachypnea, and lower abdominal/pelvic pain and tenderness in the absence of any other localizing sign of infection.¹³

Antibiotic selection

Effective treatment of endometritis requires administration of antibiotics that provide coverage against the broad range of pelvic pathogens. For many years, the gold standard of treatment has been the combination regimens of clindamycin plus gentamicin or metronidazole plus ampicillin plus gentamicin. These drugs are available in generic form and are relatively inexpensive. However, several broad-spectrum single agents are now available for treatment of endometritis. Although they are moderately more expensive than the generic combination regimens, they usually are very well tolerated, and they avoid the potential nephrotoxicity and ototoxicity associated with gentamicin. TABLE 1 summarizes the dosing regimens of these various agents and their potential weaknesses in coverage.^2,13

7. Gonorrhea

Gonorrhea is caused by the gram-negative diplococcus, Neisseria gonorrhoeae. The organism has a propensity to infect columnar epithelium and uroepithelium, and, typically, it causes a localized infection of the urethra, endocervix, and rectum. The organism also can cause an oropharyngeal infection, a disseminated infection (most commonly manifested by dermatitis and arthritis), and perihepatitis.

The diagnosis is best confirmed by a NAAT that can simultaneously test for gonorrhea and chlamydia in urine or in secretions obtained from the urethra, endocervix, and rectum.^2,10

Antibiotic selection

The drugs of choice for treating uncomplicated gonococcal infection in pregnancy are a single dose of ceftriaxone 500 mg intramuscularly, or cefixime 800 mg orally. If the patient is allergic to β-lactam antibiotics, the recommended treatment is gentamicin 240 mg intramuscularly in a single dose, combined with azithromycin 2,000 mg orally.¹⁴

8. Group B streptococci prophylaxis

The first-line agents for GBS prophylaxis are penicillin and ampicillin. Resistance of GBS to either of these antibiotics is extremely rare. The appropriate penicillin dose is 3 million U intravenously every 4 hours; the intravenous dose of ampicillin is 2 g initially, then 1 g every 4 hours. I prefer penicillin for prophylaxis because it has a narrower spectrum of activity and is less likely to cause antibiotic-associated diarrhea. The antibiotic should be continued until delivery of the neonate.^2,15,16

If the patient has a mild allergy to penicillin, the drug of choice is cefazolin 2 g intravenously initially, then 1 g every 8 hours. If the patient’s allergy to β-lactam antibiotics is severe, the alternative agents are vancomycin (20 mg/kg intravenously every 8 hours infused over 1–2 hours; maximum single dose of 2 g) and clindamycin (900 mg intravenously every 8 hours). The latter drug should be used only if sensitivity testing has confirmed that the GBS strain is sensitive to clindamycin. Resistance to clindamycin usually ranges from 10% to 15%.^2,15,16

9. Puerperal mastitis

The principal microorganisms that cause puerperal mastitis are the aerobic streptococci and staphylococci that form part of the normal skin flora. The diagnosis usually is made based on the characteristic clinical findings: erythema, tenderness, and warmth in an area of the breast accompanied by a purulent nipple discharge and fever and chills. The vast majority of cases can be treated with oral antibiotics on an outpatient basis. The key indications for hospitalization are severe illness, particularly in an immunocompromised patient, and suspicion of a breast abscess.²

Continue to: Antibiotic selection...

The initial drug of choice for treatment of mastitis is dicloxacillin sodium 500 mg every 6 hours for 7 to 10 days. If the patient has a mild allergy to penicillin, the appropriate alternative is cephalexin 500 mg every 8 hours for 7 to 10 days. If the patient’s allergy to penicillin is severe, 2 alternatives are possible. One is clindamycin 300 mg twice daily for 7 to 10 days; the other is trimethoprim-sulfamethoxazole double strength (800 mg/160 mg), twice daily for 7 to 10 days. The latter 2 drugs are also of great value if the patient fails to respond to initial therapy and/or infection with methicillin-resistant Staphylococcus aureus (MRSA) is suspected.² I prefer the latter agent because it is less expensive than clindamycin and is less likely to cause antibiotic-induced diarrhea.

If hospitalization is required, the drug of choice is intravenous vancomycin. The appropriate dosage is 20 mg/kg every 8 to 12 hours (maximum single dose of 2 g).²

10. Syphilis

Syphilis is caused by the spirochete bacterium, Treponema pallidum. The diagnosis can be made by clinical examination if the characteristic findings listed in TABLE 2 are present.^2,17 However, most patients in our practice will have latent syphilis, and the diagnosis must be established based on serologic screening.¹⁷

Antibiotic selection

In pregnancy, the treatment of choice for syphilis is penicillin (TABLE 3).^2,10,17 Only penicillin has been proven effective in treating both maternal and fetal infection. If the patient has a history of allergy to penicillin, she should undergo skin testing to determine if she is truly allergic. If hypersensitivity is confirmed, the patient should be desensitized and then treated with the appropriate regimen outlined in TABLE 3. Of interest, within a short period of time after treatment, the patient’s sensitivity to penicillin will be reestablished, and she should not be treated again with penicillin unless she undergoes another desensitization process.^2,17

11. Trichomoniasis

Trichomoniasis is caused by the flagellated protozoan, Trichomonas vaginalis. The condition is characterized by a distinct yellowish-green vaginal discharge. The vaginal pH is >4.5, and motile flagellated organisms are easily visualized on saline microscopy. The vaginal panel assay also is a valuable diagnostic test.³

Antibiotic selection

The drug of choice for trichomoniasis is oral metronidazole 500 mg twice daily for 7 days. The patient’s sexual partner(s) should be treated concurrently to prevent reinfection. Most treatment failures are due to poor compliance with therapy on the part of either the patient or her partner(s); true drug resistance is uncommon. When antibiotic resistance is strongly suspected, the patient may be treated with a single 2-g oral dose of tinidazole.²

12. Urinary tract infections

Urethritis

Acute urethritis usually is caused by C trachomatis or N gonorrhoeae. The treatment of infections with these 2 organisms is discussed above.

Asymptomatic bacteriuria and acute cystitis

Bladder infections are caused primarily by E coli, Klebsiella pneumoniae, and Proteus species. Gram-positive cocci such as enterococci, Staphylococcus saprophyticus, and GBS are less common pathogens.¹⁸

The key diagnostic criterion for asymptomatic bacteriuria is a colony count greater than 100,000 organisms/mL of a single uropathogen on a clean-catch midstream urine specimen.¹⁸

The usual clinical manifestations of acute cystitis include frequency, urgency, hesitancy, suprapubic discomfort, and a low-grade fever. The diagnosis is most effectively confirmed by obtaining urine by catheterization and demonstrating a positive nitrite and positive leukocyte esterase reaction on dipstick examination. The finding of a urine pH of 8 or greater usually indicates an infection caused by Proteus species. When urine is obtained by catheterization, the criterion for defining a positive culture is greater than 100 colonies/mL.¹⁸

Antibiotic selection. In the first trimester, the preferred agents for treatment of a lower urinary tract infection are oral amoxicillin (875 mg twice daily) or cephalexin (500 mg every 8 hours). For an initial infection, a 3-day course of therapy usually is adequate. For a recurrent infection, a 7- to 10-day course is indicated.

Beyond the first trimester, nitrofurantoin monohydrate macrocrystals (100 mg orally twice daily) or trimethoprim-sulfamethoxazole double strength (800 mg/160 mg twice daily) are the preferred agents. Unless no other oral drug is likely to be effective, these 2 drugs should be avoided in the first trimester. The former has been associated with eye, heart, and cleft defects. The latter has been associated with neural tube defects, cardiac anomalies, choanal atresia, and diaphragmatic hernia.¹⁸

Acute pyelonephritis

Acute infections of the kidney usually are caused by the aerobic gram-negative bacilli: E coli, K pneumoniae, and Proteus species. Enterococci, S saprophyticus, and GBS are less likely to cause upper tract infection as opposed to bladder infection.

The typical clinical manifestations of acute pyelonephritis include high fever and chills in association with flank pain and tenderness. The diagnosis is best confirmed by obtaining urine by catheterization and documenting the presence of a positive nitrite and leukocyte esterase reaction. Again, an elevated urine pH is indicative of an infection secondary to Proteus species. The criterion for defining a positive culture from catheterized urine is greater than 100 colonies/mL.^2,18

Antibiotic selection. Patients in the first half of pregnancy who are hemodynamically stable and who show no signs of preterm labor may be treated with oral antibiotics as outpatients. The 2 drugs of choice are amoxicillin-clavulanate (875 mg twice daily for 7 to 10 days) or trimethoprim-sulfamethoxazole double strength (800 mg/160 mg twice daily for 7 to 10 days).

For unstable patients in the first half of pregnancy and for essentially all patients in the second half of pregnancy, parenteral treatment should be administered on an inpatient basis. My preference for treatment is ceftriaxone, 2 g intravenously every 24 hours. The drug provides excellent coverage against almost all the uropathogens. It has a convenient dosing schedule, and it usually is very well tolerated. Parenteral therapy should be continued until the patient has been afebrile and asymptomatic for 24 to 48 hours. At this point, the patient can be transitioned to one of the oral regimens listed above and managed as an outpatient. If the patient is allergic to β-lactam antibiotics, an excellent alternative is aztreonam, 2 g intravenously every 8 hours.^2,18 ●

For the infections we most commonly encounter in obstetric practice, I review in this article the selection of specific antibiotics. I focus on the key pathogens that cause these infections, the most useful diagnostic tests, and the most cost-effective antibiotic therapy. Relative cost estimates (high vs low) for drugs are based on information published on the GoodRx website (https://www.goodrx.com/). Actual charges to patients, of course, may vary widely depending on contractual relationships between hospitals, insurance companies, and wholesale vendors. The infections are listed in alphabetical order, not in order of frequency or severity.

1. Bacterial vaginosis

Bacterial vaginosis (BV) is a polymicrobial infection that results from perturbation of the normal vaginal flora due to conditions such as pregnancy, hormonal therapy, and changes in the menstrual cycle. It is characterized by a decrease in the vaginal concentration of Lactobacillus crispatus, followed by an increase in Prevotella bivia, Gardnerella vaginalis, Mobiluncus species, Atopobium vaginae, and Megasphaera type 1.^1,2

BV is characterized by a thin, white-gray malodorous (fishlike smell) discharge. The vaginal pH is >4.5. Clue cells are apparent on saline microscopy, and the whiff (amine) test is positive when potassium hydroxide is added to a drop of vaginal secretions. Diagnostic accuracy can be improved using one of the new vaginal panel assays such as BD MAX Vaginal Panel (Becton, Dickinson and Company).³

Antibiotic selection

Antibiotic treatment of BV is directed primarily at the anaerobic component of the infection. The preferred treatment is oral metronidazole 500 mg twice daily for 7 days. If the patient cannot tolerate metronidazole, oral clindamycin 300 mg twice daily for 7 days, can be used, although it is more expensive than metronidazole. Topical metronidazole vaginal gel (0.75%), 1 applicatorful daily for 5 days, is effective in treating the local vaginal infection, but it is not effective in preventing systemic complications such as preterm labor, chorioamnionitis, and puerperal endometritis.² It also is significantly more expensive than the oral formulation of metronidazole. Topical clindamycin cream, 1 applicatorful daily for 5 days, is even more expensive.

Tinidazole 2 g orally daily for 2 days is an effective alternative to oral metronidazole. Single-dose therapy with oral secnidazole (2 g), a 5-nitroimidazole with a longer half-life than metronidazole, has been effective in small studies, but experience with this drug in the United States is limited. Secnidazole is also very expensive.⁴

2. Candidiasis

Vulvovaginal candidiasis usually is caused by Candida albicans. Other less common species include C tropicalis, C glabrata, C auris, C lusitaniae, and C krusei. The most common clinical findings are vulvovaginal pruritus in association with a curdlike white vaginal discharge. The diagnosis can be established by confirmation of a normal vaginal pH and identification of budding yeast and hyphae on a potassium hydroxide preparation. As noted above for BV, the vaginal panel assay improves the accuracy of clinical diagnosis.³ Culture usually is indicated only in patients with infections that are refractory to therapy.

Continue to: Antibiotic selection...

Antibiotic selection

In the first trimester of pregnancy, vulvovaginal candidiasis should be treated with a topical medication such as clotrimazole cream 1% (50 mg intravaginally daily for 7 days), miconazole cream 2% (100 mg intravaginally daily for 7 days), or terconazole cream 0.4% (50 g intravaginally daily for 7 days). Single-dose formulations or 3-day courses of treatment may not be quite as effective in pregnant patients, but they do offer a more convenient dosing schedule.^2,5

Oral fluconazole should not be used in the first trimester of pregnancy because it has been associated with an increased risk for spontaneous abortion and with fetal cardiac septal defects. Beyond the first trimester, oral fluconazole offers an attractive option for treatment of vulvovaginal candidiasis. The appropriate dose is 150 mg initially, with a repeat dose in 3 days if symptoms persist.^2,5

Ibrexafungerp (300 mg twice daily for 1 day) was recently approved by the US Food and Drug Administration (FDA) for oral treatment of vulvovaginal candidiasis. However, this drug is teratogenic and is contraindicated during pregnancy and lactation. It also is significantly more expensive than fluconazole.⁶

3. Cesarean delivery prophylaxis

All women having a cesarean delivery (CD) should receive antibiotic prophylaxis to reduce the risk of endometritis and wound infection.

Antibiotic selection

In my opinion, the preferred regimen is intravenous cefazolin 2 g plus azithromycin 500 mg administered preoperatively.⁷ Cefazolin can be administered in a rapid bolus; azithromycin should be administered over 1 hour.

In an exceptionally rigorous investigation called the C/SOAP trial (Cesarean Section Optimal Antibiotic Prophylaxis trial), Tita and colleagues showed that the combination of cefazolin plus azithromycin was superior to single-agent prophylaxis (usually with cefazolin) in preventing the composite of endometritis, wound infection, or other infection occurring within 6 weeks of surgery.⁸ The additive effect of azithromycin was particularly pronounced in patients having CD after labor and rupture of membranes. Harper and associates subsequently validated the cost-effectiveness of this combination regimen using a decision analytic model.⁹

If the patient has a serious allergy to β-lactam antibiotics, the best alternative regimen for prophylaxis is clindamycin plus gentamicin. The appropriate single intravenous dose of clindamycin is 900 mg; the single dose of gentamicin should be 5 mg/kg of ideal body weight (IBW).⁷

4. Chlamydia

Chlamydia trachomatis is an obligate intracellular bacterium. In pregnant women, it typically causes urethritis, endocervicitis, and inflammatory proctitis. Along with gonorrhea, it is the cause of an unusual infection/inflammation of the liver capsule, termed Fitz-Hugh-Curtis syndrome (perihepatitis). The diagnosis of chlamydia infection is best confirmed with a nucleic acid amplification test (NAAT). The NAAT simultaneously tests for chlamydia and gonorrhea in urine or in secretions obtained from the urethra, endocervix, and rectum.²

Antibiotic selection

The drug of choice for treating chlamydia in pregnancy is azithromycin 1,000 mg orally in a single dose. Erythromycin can be used as an alternative to azithromycin, but it usually is not well tolerated because of gastrointestinal adverse effects. In my practice, the preferred alternative for a patient who cannot tolerate azithromycin is amoxicillin 500 mg orally 3 times daily for 7 days.^2,10

Continue to: 5. Chorioamnionitis...

5. Chorioamnionitis

Chorioamnionitis is a polymicrobial infection caused by anaerobes, aerobic gram-negative bacilli (predominantly Escherichia coli), and aerobic gram-positive cocci (primarily group B streptococci [GBS]). The diagnosis usually is made based on clinical examination: maternal fever, maternal and fetal tachycardia, and no other localizing sign of infection. The diagnosis can be confirmed by obtaining a sample of amniotic fluid via amniocentesis or via aspiration through the intrauterine pressure catheter and demonstrating a positive Gram stain, low glucose concentration (<20 mg/dL), positive nitrites, positive leukocyte esterase, and ultimately, a positive bacteriologic culture.²

Antibiotic selection

The initial treatment of chorioamnionitis specifically targets the 2 major organisms that cause neonatal pneumonia, meningitis, and sepsis: GBS and E coli. For many years, the drugs of choice have been intravenous ampicillin (2 g every 6 hours) plus intravenous gentamicin (5 mg/kg of IBW every 24 hours). Gentamicin also can be administered intravenously at a dose of 1.5 mg/kg every 8 hours. I prefer the once-daily dosing for 3 reasons:

• Gentamicin works by a concentration-dependent mechanism; the higher the initial serum concentration, the better the killing effect.
• Once-daily dosing preserves long periods with low trough levels, an effect that minimizes ototoxicity and nephrotoxicity.
• Once-daily dosing is more convenient.

In a patient who has a contraindication to use of an aminoglycoside, aztreonam (2 g intravenously every 8 hours) may be combined with ampicillin.²

If the patient delivers vaginally, 1 dose of each drug should be administered postpartum, and then the antibiotics should be discontinued. If the patient delivers by cesarean, a single dose of a medication with strong anaerobic coverage should be administered immediately after the infant’s umbilical cord is clamped. Options include clindamycin (900 mg intravenously) or metronidazole (500 mg intravenously).¹¹

There are 2 key exceptions to the single postpartum dose rule, however. If the patient is obese (body mass index [BMI] >30 kg/m²) or if the membranes have been ruptured for more than 24 hours, antibiotics should be continued until she has been afebrile and asymptomatic for 24 hours.¹²

Two single agents are excellent alternatives to the combination ampicillin-gentamicin regimen. One is ampicillin-sulbactam, 3 g intravenously every 6 hours. The other is piperacillin-tazobactam, 3.375 g intravenously every 6 hours. These extended-spectrum penicillins provide exceptionally good coverage against the major pathogens that cause chorioamnionitis. Although more expensive than the combination regimen, they avoid the potential ototoxicity and nephrotoxicity associated with gentamicin.²

6. Endometritis

Puerperal endometritis is significantly more common after CD than after vaginal delivery. The infection is polymicrobial, and the principal pathogens are anaerobic gram-positive cocci, anaerobic gram-negative bacilli, aerobic gram-negative bacilli, and aerobic gram-positive cocci. The diagnosis usually is made almost exclusively based on clinical findings: fever within 24 to 36 hours of delivery, tachycardia, mild tachypnea, and lower abdominal/pelvic pain and tenderness in the absence of any other localizing sign of infection.¹³

Antibiotic selection

Effective treatment of endometritis requires administration of antibiotics that provide coverage against the broad range of pelvic pathogens. For many years, the gold standard of treatment has been the combination regimens of clindamycin plus gentamicin or metronidazole plus ampicillin plus gentamicin. These drugs are available in generic form and are relatively inexpensive. However, several broad-spectrum single agents are now available for treatment of endometritis. Although they are moderately more expensive than the generic combination regimens, they usually are very well tolerated, and they avoid the potential nephrotoxicity and ototoxicity associated with gentamicin. TABLE 1 summarizes the dosing regimens of these various agents and their potential weaknesses in coverage.^2,13

7. Gonorrhea

Gonorrhea is caused by the gram-negative diplococcus, Neisseria gonorrhoeae. The organism has a propensity to infect columnar epithelium and uroepithelium, and, typically, it causes a localized infection of the urethra, endocervix, and rectum. The organism also can cause an oropharyngeal infection, a disseminated infection (most commonly manifested by dermatitis and arthritis), and perihepatitis.

The diagnosis is best confirmed by a NAAT that can simultaneously test for gonorrhea and chlamydia in urine or in secretions obtained from the urethra, endocervix, and rectum.^2,10

Antibiotic selection

The drugs of choice for treating uncomplicated gonococcal infection in pregnancy are a single dose of ceftriaxone 500 mg intramuscularly, or cefixime 800 mg orally. If the patient is allergic to β-lactam antibiotics, the recommended treatment is gentamicin 240 mg intramuscularly in a single dose, combined with azithromycin 2,000 mg orally.¹⁴

8. Group B streptococci prophylaxis

The first-line agents for GBS prophylaxis are penicillin and ampicillin. Resistance of GBS to either of these antibiotics is extremely rare. The appropriate penicillin dose is 3 million U intravenously every 4 hours; the intravenous dose of ampicillin is 2 g initially, then 1 g every 4 hours. I prefer penicillin for prophylaxis because it has a narrower spectrum of activity and is less likely to cause antibiotic-associated diarrhea. The antibiotic should be continued until delivery of the neonate.^2,15,16

If the patient has a mild allergy to penicillin, the drug of choice is cefazolin 2 g intravenously initially, then 1 g every 8 hours. If the patient’s allergy to β-lactam antibiotics is severe, the alternative agents are vancomycin (20 mg/kg intravenously every 8 hours infused over 1–2 hours; maximum single dose of 2 g) and clindamycin (900 mg intravenously every 8 hours). The latter drug should be used only if sensitivity testing has confirmed that the GBS strain is sensitive to clindamycin. Resistance to clindamycin usually ranges from 10% to 15%.^2,15,16

9. Puerperal mastitis

The principal microorganisms that cause puerperal mastitis are the aerobic streptococci and staphylococci that form part of the normal skin flora. The diagnosis usually is made based on the characteristic clinical findings: erythema, tenderness, and warmth in an area of the breast accompanied by a purulent nipple discharge and fever and chills. The vast majority of cases can be treated with oral antibiotics on an outpatient basis. The key indications for hospitalization are severe illness, particularly in an immunocompromised patient, and suspicion of a breast abscess.²

Continue to: Antibiotic selection...

The initial drug of choice for treatment of mastitis is dicloxacillin sodium 500 mg every 6 hours for 7 to 10 days. If the patient has a mild allergy to penicillin, the appropriate alternative is cephalexin 500 mg every 8 hours for 7 to 10 days. If the patient’s allergy to penicillin is severe, 2 alternatives are possible. One is clindamycin 300 mg twice daily for 7 to 10 days; the other is trimethoprim-sulfamethoxazole double strength (800 mg/160 mg), twice daily for 7 to 10 days. The latter 2 drugs are also of great value if the patient fails to respond to initial therapy and/or infection with methicillin-resistant Staphylococcus aureus (MRSA) is suspected.² I prefer the latter agent because it is less expensive than clindamycin and is less likely to cause antibiotic-induced diarrhea.

If hospitalization is required, the drug of choice is intravenous vancomycin. The appropriate dosage is 20 mg/kg every 8 to 12 hours (maximum single dose of 2 g).²

10. Syphilis

Syphilis is caused by the spirochete bacterium, Treponema pallidum. The diagnosis can be made by clinical examination if the characteristic findings listed in TABLE 2 are present.^2,17 However, most patients in our practice will have latent syphilis, and the diagnosis must be established based on serologic screening.¹⁷

Antibiotic selection

In pregnancy, the treatment of choice for syphilis is penicillin (TABLE 3).^2,10,17 Only penicillin has been proven effective in treating both maternal and fetal infection. If the patient has a history of allergy to penicillin, she should undergo skin testing to determine if she is truly allergic. If hypersensitivity is confirmed, the patient should be desensitized and then treated with the appropriate regimen outlined in TABLE 3. Of interest, within a short period of time after treatment, the patient’s sensitivity to penicillin will be reestablished, and she should not be treated again with penicillin unless she undergoes another desensitization process.^2,17

11. Trichomoniasis

Trichomoniasis is caused by the flagellated protozoan, Trichomonas vaginalis. The condition is characterized by a distinct yellowish-green vaginal discharge. The vaginal pH is >4.5, and motile flagellated organisms are easily visualized on saline microscopy. The vaginal panel assay also is a valuable diagnostic test.³

Antibiotic selection

The drug of choice for trichomoniasis is oral metronidazole 500 mg twice daily for 7 days. The patient’s sexual partner(s) should be treated concurrently to prevent reinfection. Most treatment failures are due to poor compliance with therapy on the part of either the patient or her partner(s); true drug resistance is uncommon. When antibiotic resistance is strongly suspected, the patient may be treated with a single 2-g oral dose of tinidazole.²

12. Urinary tract infections

Urethritis

Acute urethritis usually is caused by C trachomatis or N gonorrhoeae. The treatment of infections with these 2 organisms is discussed above.

Asymptomatic bacteriuria and acute cystitis

Bladder infections are caused primarily by E coli, Klebsiella pneumoniae, and Proteus species. Gram-positive cocci such as enterococci, Staphylococcus saprophyticus, and GBS are less common pathogens.¹⁸

The key diagnostic criterion for asymptomatic bacteriuria is a colony count greater than 100,000 organisms/mL of a single uropathogen on a clean-catch midstream urine specimen.¹⁸

The usual clinical manifestations of acute cystitis include frequency, urgency, hesitancy, suprapubic discomfort, and a low-grade fever. The diagnosis is most effectively confirmed by obtaining urine by catheterization and demonstrating a positive nitrite and positive leukocyte esterase reaction on dipstick examination. The finding of a urine pH of 8 or greater usually indicates an infection caused by Proteus species. When urine is obtained by catheterization, the criterion for defining a positive culture is greater than 100 colonies/mL.¹⁸

Antibiotic selection. In the first trimester, the preferred agents for treatment of a lower urinary tract infection are oral amoxicillin (875 mg twice daily) or cephalexin (500 mg every 8 hours). For an initial infection, a 3-day course of therapy usually is adequate. For a recurrent infection, a 7- to 10-day course is indicated.

Beyond the first trimester, nitrofurantoin monohydrate macrocrystals (100 mg orally twice daily) or trimethoprim-sulfamethoxazole double strength (800 mg/160 mg twice daily) are the preferred agents. Unless no other oral drug is likely to be effective, these 2 drugs should be avoided in the first trimester. The former has been associated with eye, heart, and cleft defects. The latter has been associated with neural tube defects, cardiac anomalies, choanal atresia, and diaphragmatic hernia.¹⁸

Acute pyelonephritis

Acute infections of the kidney usually are caused by the aerobic gram-negative bacilli: E coli, K pneumoniae, and Proteus species. Enterococci, S saprophyticus, and GBS are less likely to cause upper tract infection as opposed to bladder infection.

The typical clinical manifestations of acute pyelonephritis include high fever and chills in association with flank pain and tenderness. The diagnosis is best confirmed by obtaining urine by catheterization and documenting the presence of a positive nitrite and leukocyte esterase reaction. Again, an elevated urine pH is indicative of an infection secondary to Proteus species. The criterion for defining a positive culture from catheterized urine is greater than 100 colonies/mL.^2,18

Antibiotic selection. Patients in the first half of pregnancy who are hemodynamically stable and who show no signs of preterm labor may be treated with oral antibiotics as outpatients. The 2 drugs of choice are amoxicillin-clavulanate (875 mg twice daily for 7 to 10 days) or trimethoprim-sulfamethoxazole double strength (800 mg/160 mg twice daily for 7 to 10 days).

For unstable patients in the first half of pregnancy and for essentially all patients in the second half of pregnancy, parenteral treatment should be administered on an inpatient basis. My preference for treatment is ceftriaxone, 2 g intravenously every 24 hours. The drug provides excellent coverage against almost all the uropathogens. It has a convenient dosing schedule, and it usually is very well tolerated. Parenteral therapy should be continued until the patient has been afebrile and asymptomatic for 24 to 48 hours. At this point, the patient can be transitioned to one of the oral regimens listed above and managed as an outpatient. If the patient is allergic to β-lactam antibiotics, an excellent alternative is aztreonam, 2 g intravenously every 8 hours.^2,18 ●

For the infections we most commonly encounter in obstetric practice, I review in this article the selection of specific antibiotics. I focus on the key pathogens that cause these infections, the most useful diagnostic tests, and the most cost-effective antibiotic therapy. Relative cost estimates (high vs low) for drugs are based on information published on the GoodRx website (https://www.goodrx.com/). Actual charges to patients, of course, may vary widely depending on contractual relationships between hospitals, insurance companies, and wholesale vendors. The infections are listed in alphabetical order, not in order of frequency or severity.

1. Bacterial vaginosis

Bacterial vaginosis (BV) is a polymicrobial infection that results from perturbation of the normal vaginal flora due to conditions such as pregnancy, hormonal therapy, and changes in the menstrual cycle. It is characterized by a decrease in the vaginal concentration of Lactobacillus crispatus, followed by an increase in Prevotella bivia, Gardnerella vaginalis, Mobiluncus species, Atopobium vaginae, and Megasphaera type 1.^1,2

BV is characterized by a thin, white-gray malodorous (fishlike smell) discharge. The vaginal pH is >4.5. Clue cells are apparent on saline microscopy, and the whiff (amine) test is positive when potassium hydroxide is added to a drop of vaginal secretions. Diagnostic accuracy can be improved using one of the new vaginal panel assays such as BD MAX Vaginal Panel (Becton, Dickinson and Company).³

Antibiotic selection

Antibiotic treatment of BV is directed primarily at the anaerobic component of the infection. The preferred treatment is oral metronidazole 500 mg twice daily for 7 days. If the patient cannot tolerate metronidazole, oral clindamycin 300 mg twice daily for 7 days, can be used, although it is more expensive than metronidazole. Topical metronidazole vaginal gel (0.75%), 1 applicatorful daily for 5 days, is effective in treating the local vaginal infection, but it is not effective in preventing systemic complications such as preterm labor, chorioamnionitis, and puerperal endometritis.² It also is significantly more expensive than the oral formulation of metronidazole. Topical clindamycin cream, 1 applicatorful daily for 5 days, is even more expensive.

Tinidazole 2 g orally daily for 2 days is an effective alternative to oral metronidazole. Single-dose therapy with oral secnidazole (2 g), a 5-nitroimidazole with a longer half-life than metronidazole, has been effective in small studies, but experience with this drug in the United States is limited. Secnidazole is also very expensive.⁴

2. Candidiasis

Vulvovaginal candidiasis usually is caused by Candida albicans. Other less common species include C tropicalis, C glabrata, C auris, C lusitaniae, and C krusei. The most common clinical findings are vulvovaginal pruritus in association with a curdlike white vaginal discharge. The diagnosis can be established by confirmation of a normal vaginal pH and identification of budding yeast and hyphae on a potassium hydroxide preparation. As noted above for BV, the vaginal panel assay improves the accuracy of clinical diagnosis.³ Culture usually is indicated only in patients with infections that are refractory to therapy.

Continue to: Antibiotic selection...

Antibiotic selection

In the first trimester of pregnancy, vulvovaginal candidiasis should be treated with a topical medication such as clotrimazole cream 1% (50 mg intravaginally daily for 7 days), miconazole cream 2% (100 mg intravaginally daily for 7 days), or terconazole cream 0.4% (50 g intravaginally daily for 7 days). Single-dose formulations or 3-day courses of treatment may not be quite as effective in pregnant patients, but they do offer a more convenient dosing schedule.^2,5

Oral fluconazole should not be used in the first trimester of pregnancy because it has been associated with an increased risk for spontaneous abortion and with fetal cardiac septal defects. Beyond the first trimester, oral fluconazole offers an attractive option for treatment of vulvovaginal candidiasis. The appropriate dose is 150 mg initially, with a repeat dose in 3 days if symptoms persist.^2,5

Ibrexafungerp (300 mg twice daily for 1 day) was recently approved by the US Food and Drug Administration (FDA) for oral treatment of vulvovaginal candidiasis. However, this drug is teratogenic and is contraindicated during pregnancy and lactation. It also is significantly more expensive than fluconazole.⁶

3. Cesarean delivery prophylaxis

All women having a cesarean delivery (CD) should receive antibiotic prophylaxis to reduce the risk of endometritis and wound infection.

Antibiotic selection

In my opinion, the preferred regimen is intravenous cefazolin 2 g plus azithromycin 500 mg administered preoperatively.⁷ Cefazolin can be administered in a rapid bolus; azithromycin should be administered over 1 hour.

In an exceptionally rigorous investigation called the C/SOAP trial (Cesarean Section Optimal Antibiotic Prophylaxis trial), Tita and colleagues showed that the combination of cefazolin plus azithromycin was superior to single-agent prophylaxis (usually with cefazolin) in preventing the composite of endometritis, wound infection, or other infection occurring within 6 weeks of surgery.⁸ The additive effect of azithromycin was particularly pronounced in patients having CD after labor and rupture of membranes. Harper and associates subsequently validated the cost-effectiveness of this combination regimen using a decision analytic model.⁹

If the patient has a serious allergy to β-lactam antibiotics, the best alternative regimen for prophylaxis is clindamycin plus gentamicin. The appropriate single intravenous dose of clindamycin is 900 mg; the single dose of gentamicin should be 5 mg/kg of ideal body weight (IBW).⁷

4. Chlamydia

Chlamydia trachomatis is an obligate intracellular bacterium. In pregnant women, it typically causes urethritis, endocervicitis, and inflammatory proctitis. Along with gonorrhea, it is the cause of an unusual infection/inflammation of the liver capsule, termed Fitz-Hugh-Curtis syndrome (perihepatitis). The diagnosis of chlamydia infection is best confirmed with a nucleic acid amplification test (NAAT). The NAAT simultaneously tests for chlamydia and gonorrhea in urine or in secretions obtained from the urethra, endocervix, and rectum.²

Antibiotic selection

The drug of choice for treating chlamydia in pregnancy is azithromycin 1,000 mg orally in a single dose. Erythromycin can be used as an alternative to azithromycin, but it usually is not well tolerated because of gastrointestinal adverse effects. In my practice, the preferred alternative for a patient who cannot tolerate azithromycin is amoxicillin 500 mg orally 3 times daily for 7 days.^2,10

Continue to: 5. Chorioamnionitis...

5. Chorioamnionitis

Chorioamnionitis is a polymicrobial infection caused by anaerobes, aerobic gram-negative bacilli (predominantly Escherichia coli), and aerobic gram-positive cocci (primarily group B streptococci [GBS]). The diagnosis usually is made based on clinical examination: maternal fever, maternal and fetal tachycardia, and no other localizing sign of infection. The diagnosis can be confirmed by obtaining a sample of amniotic fluid via amniocentesis or via aspiration through the intrauterine pressure catheter and demonstrating a positive Gram stain, low glucose concentration (<20 mg/dL), positive nitrites, positive leukocyte esterase, and ultimately, a positive bacteriologic culture.²

Antibiotic selection

The initial treatment of chorioamnionitis specifically targets the 2 major organisms that cause neonatal pneumonia, meningitis, and sepsis: GBS and E coli. For many years, the drugs of choice have been intravenous ampicillin (2 g every 6 hours) plus intravenous gentamicin (5 mg/kg of IBW every 24 hours). Gentamicin also can be administered intravenously at a dose of 1.5 mg/kg every 8 hours. I prefer the once-daily dosing for 3 reasons:

• Gentamicin works by a concentration-dependent mechanism; the higher the initial serum concentration, the better the killing effect.
• Once-daily dosing preserves long periods with low trough levels, an effect that minimizes ototoxicity and nephrotoxicity.
• Once-daily dosing is more convenient.

In a patient who has a contraindication to use of an aminoglycoside, aztreonam (2 g intravenously every 8 hours) may be combined with ampicillin.²

If the patient delivers vaginally, 1 dose of each drug should be administered postpartum, and then the antibiotics should be discontinued. If the patient delivers by cesarean, a single dose of a medication with strong anaerobic coverage should be administered immediately after the infant’s umbilical cord is clamped. Options include clindamycin (900 mg intravenously) or metronidazole (500 mg intravenously).¹¹

There are 2 key exceptions to the single postpartum dose rule, however. If the patient is obese (body mass index [BMI] >30 kg/m²) or if the membranes have been ruptured for more than 24 hours, antibiotics should be continued until she has been afebrile and asymptomatic for 24 hours.¹²

Two single agents are excellent alternatives to the combination ampicillin-gentamicin regimen. One is ampicillin-sulbactam, 3 g intravenously every 6 hours. The other is piperacillin-tazobactam, 3.375 g intravenously every 6 hours. These extended-spectrum penicillins provide exceptionally good coverage against the major pathogens that cause chorioamnionitis. Although more expensive than the combination regimen, they avoid the potential ototoxicity and nephrotoxicity associated with gentamicin.²

6. Endometritis

Puerperal endometritis is significantly more common after CD than after vaginal delivery. The infection is polymicrobial, and the principal pathogens are anaerobic gram-positive cocci, anaerobic gram-negative bacilli, aerobic gram-negative bacilli, and aerobic gram-positive cocci. The diagnosis usually is made almost exclusively based on clinical findings: fever within 24 to 36 hours of delivery, tachycardia, mild tachypnea, and lower abdominal/pelvic pain and tenderness in the absence of any other localizing sign of infection.¹³

Antibiotic selection

Effective treatment of endometritis requires administration of antibiotics that provide coverage against the broad range of pelvic pathogens. For many years, the gold standard of treatment has been the combination regimens of clindamycin plus gentamicin or metronidazole plus ampicillin plus gentamicin. These drugs are available in generic form and are relatively inexpensive. However, several broad-spectrum single agents are now available for treatment of endometritis. Although they are moderately more expensive than the generic combination regimens, they usually are very well tolerated, and they avoid the potential nephrotoxicity and ototoxicity associated with gentamicin. TABLE 1 summarizes the dosing regimens of these various agents and their potential weaknesses in coverage.^2,13

7. Gonorrhea

Gonorrhea is caused by the gram-negative diplococcus, Neisseria gonorrhoeae. The organism has a propensity to infect columnar epithelium and uroepithelium, and, typically, it causes a localized infection of the urethra, endocervix, and rectum. The organism also can cause an oropharyngeal infection, a disseminated infection (most commonly manifested by dermatitis and arthritis), and perihepatitis.

The diagnosis is best confirmed by a NAAT that can simultaneously test for gonorrhea and chlamydia in urine or in secretions obtained from the urethra, endocervix, and rectum.^2,10

Antibiotic selection

The drugs of choice for treating uncomplicated gonococcal infection in pregnancy are a single dose of ceftriaxone 500 mg intramuscularly, or cefixime 800 mg orally. If the patient is allergic to β-lactam antibiotics, the recommended treatment is gentamicin 240 mg intramuscularly in a single dose, combined with azithromycin 2,000 mg orally.¹⁴

8. Group B streptococci prophylaxis

The first-line agents for GBS prophylaxis are penicillin and ampicillin. Resistance of GBS to either of these antibiotics is extremely rare. The appropriate penicillin dose is 3 million U intravenously every 4 hours; the intravenous dose of ampicillin is 2 g initially, then 1 g every 4 hours. I prefer penicillin for prophylaxis because it has a narrower spectrum of activity and is less likely to cause antibiotic-associated diarrhea. The antibiotic should be continued until delivery of the neonate.^2,15,16

If the patient has a mild allergy to penicillin, the drug of choice is cefazolin 2 g intravenously initially, then 1 g every 8 hours. If the patient’s allergy to β-lactam antibiotics is severe, the alternative agents are vancomycin (20 mg/kg intravenously every 8 hours infused over 1–2 hours; maximum single dose of 2 g) and clindamycin (900 mg intravenously every 8 hours). The latter drug should be used only if sensitivity testing has confirmed that the GBS strain is sensitive to clindamycin. Resistance to clindamycin usually ranges from 10% to 15%.^2,15,16

9. Puerperal mastitis

The principal microorganisms that cause puerperal mastitis are the aerobic streptococci and staphylococci that form part of the normal skin flora. The diagnosis usually is made based on the characteristic clinical findings: erythema, tenderness, and warmth in an area of the breast accompanied by a purulent nipple discharge and fever and chills. The vast majority of cases can be treated with oral antibiotics on an outpatient basis. The key indications for hospitalization are severe illness, particularly in an immunocompromised patient, and suspicion of a breast abscess.²

Continue to: Antibiotic selection...

The initial drug of choice for treatment of mastitis is dicloxacillin sodium 500 mg every 6 hours for 7 to 10 days. If the patient has a mild allergy to penicillin, the appropriate alternative is cephalexin 500 mg every 8 hours for 7 to 10 days. If the patient’s allergy to penicillin is severe, 2 alternatives are possible. One is clindamycin 300 mg twice daily for 7 to 10 days; the other is trimethoprim-sulfamethoxazole double strength (800 mg/160 mg), twice daily for 7 to 10 days. The latter 2 drugs are also of great value if the patient fails to respond to initial therapy and/or infection with methicillin-resistant Staphylococcus aureus (MRSA) is suspected.² I prefer the latter agent because it is less expensive than clindamycin and is less likely to cause antibiotic-induced diarrhea.

If hospitalization is required, the drug of choice is intravenous vancomycin. The appropriate dosage is 20 mg/kg every 8 to 12 hours (maximum single dose of 2 g).²

10. Syphilis

Syphilis is caused by the spirochete bacterium, Treponema pallidum. The diagnosis can be made by clinical examination if the characteristic findings listed in TABLE 2 are present.^2,17 However, most patients in our practice will have latent syphilis, and the diagnosis must be established based on serologic screening.¹⁷

Antibiotic selection

In pregnancy, the treatment of choice for syphilis is penicillin (TABLE 3).^2,10,17 Only penicillin has been proven effective in treating both maternal and fetal infection. If the patient has a history of allergy to penicillin, she should undergo skin testing to determine if she is truly allergic. If hypersensitivity is confirmed, the patient should be desensitized and then treated with the appropriate regimen outlined in TABLE 3. Of interest, within a short period of time after treatment, the patient’s sensitivity to penicillin will be reestablished, and she should not be treated again with penicillin unless she undergoes another desensitization process.^2,17

11. Trichomoniasis

Trichomoniasis is caused by the flagellated protozoan, Trichomonas vaginalis. The condition is characterized by a distinct yellowish-green vaginal discharge. The vaginal pH is >4.5, and motile flagellated organisms are easily visualized on saline microscopy. The vaginal panel assay also is a valuable diagnostic test.³

Antibiotic selection

The drug of choice for trichomoniasis is oral metronidazole 500 mg twice daily for 7 days. The patient’s sexual partner(s) should be treated concurrently to prevent reinfection. Most treatment failures are due to poor compliance with therapy on the part of either the patient or her partner(s); true drug resistance is uncommon. When antibiotic resistance is strongly suspected, the patient may be treated with a single 2-g oral dose of tinidazole.²

12. Urinary tract infections

Urethritis

Acute urethritis usually is caused by C trachomatis or N gonorrhoeae. The treatment of infections with these 2 organisms is discussed above.

Asymptomatic bacteriuria and acute cystitis

Bladder infections are caused primarily by E coli, Klebsiella pneumoniae, and Proteus species. Gram-positive cocci such as enterococci, Staphylococcus saprophyticus, and GBS are less common pathogens.¹⁸

The key diagnostic criterion for asymptomatic bacteriuria is a colony count greater than 100,000 organisms/mL of a single uropathogen on a clean-catch midstream urine specimen.¹⁸

The usual clinical manifestations of acute cystitis include frequency, urgency, hesitancy, suprapubic discomfort, and a low-grade fever. The diagnosis is most effectively confirmed by obtaining urine by catheterization and demonstrating a positive nitrite and positive leukocyte esterase reaction on dipstick examination. The finding of a urine pH of 8 or greater usually indicates an infection caused by Proteus species. When urine is obtained by catheterization, the criterion for defining a positive culture is greater than 100 colonies/mL.¹⁸

Antibiotic selection. In the first trimester, the preferred agents for treatment of a lower urinary tract infection are oral amoxicillin (875 mg twice daily) or cephalexin (500 mg every 8 hours). For an initial infection, a 3-day course of therapy usually is adequate. For a recurrent infection, a 7- to 10-day course is indicated.

Beyond the first trimester, nitrofurantoin monohydrate macrocrystals (100 mg orally twice daily) or trimethoprim-sulfamethoxazole double strength (800 mg/160 mg twice daily) are the preferred agents. Unless no other oral drug is likely to be effective, these 2 drugs should be avoided in the first trimester. The former has been associated with eye, heart, and cleft defects. The latter has been associated with neural tube defects, cardiac anomalies, choanal atresia, and diaphragmatic hernia.¹⁸

Acute pyelonephritis

Acute infections of the kidney usually are caused by the aerobic gram-negative bacilli: E coli, K pneumoniae, and Proteus species. Enterococci, S saprophyticus, and GBS are less likely to cause upper tract infection as opposed to bladder infection.

The typical clinical manifestations of acute pyelonephritis include high fever and chills in association with flank pain and tenderness. The diagnosis is best confirmed by obtaining urine by catheterization and documenting the presence of a positive nitrite and leukocyte esterase reaction. Again, an elevated urine pH is indicative of an infection secondary to Proteus species. The criterion for defining a positive culture from catheterized urine is greater than 100 colonies/mL.^2,18

Antibiotic selection. Patients in the first half of pregnancy who are hemodynamically stable and who show no signs of preterm labor may be treated with oral antibiotics as outpatients. The 2 drugs of choice are amoxicillin-clavulanate (875 mg twice daily for 7 to 10 days) or trimethoprim-sulfamethoxazole double strength (800 mg/160 mg twice daily for 7 to 10 days).

For unstable patients in the first half of pregnancy and for essentially all patients in the second half of pregnancy, parenteral treatment should be administered on an inpatient basis. My preference for treatment is ceftriaxone, 2 g intravenously every 24 hours. The drug provides excellent coverage against almost all the uropathogens. It has a convenient dosing schedule, and it usually is very well tolerated. Parenteral therapy should be continued until the patient has been afebrile and asymptomatic for 24 to 48 hours. At this point, the patient can be transitioned to one of the oral regimens listed above and managed as an outpatient. If the patient is allergic to β-lactam antibiotics, an excellent alternative is aztreonam, 2 g intravenously every 8 hours.^2,18 ●

ILLUSTRATION BY KIMBERLY MARTENS FOR OBG MANAGEMENT

CASE Part 1: CPR initiated during induction of labor

A 32-year-old gravida 4 para 3-0-0-3 is undergoing induction of labor with intravenous (IV) oxytocin at 39 weeks of gestation. She has no significant medical or obstetric history. Fifteen minutes after reaching complete cervical dilation, she says “I don’t feel right,” then suddenly loses consciousness. The nurse finds no detectable pulse, calls a “code blue,” and initiates cardiopulmonary resuscitation (CPR). The obstetrician is notified, appears promptly, assesses the situation, and delivers a 3.6-kg baby via vacuum extraction. Apgar score is 2/10 at 1 minute and 6/10 at 5 minutes. After delivery of the placenta, there is uterine atony and brisk hemorrhage with 2 L of blood loss.

Management of AFE: A rare complication

This case demonstrates a classic presentation of amniotic fluid embolism (AFE) syndrome—a patient in labor or within 30 minutes after delivery has sudden onset of cardiorespiratory collapse followed by disseminated intravascular coagulation (DIC). AFE is rare, affecting only about 2 to 6 per 100,000 births, but classic cases have a reported maternal mortality rate that exceeds 50%.¹ It is thought to reflect a complex, systemic proinflammatory response to maternal intravasation of pregnancy material, such as trophoblast, thromboplastins, fetal cells, or amniotic fluid. Because the syndrome is not necessarily directly caused by emboli or by amniotic fluid per se,² it has been proposed that AFE be called “anaphylactoid syndrome of pregnancy,” but this terminology has not yet been widely adopted.³

Guidelines from the Society for Maternal-Fetal Medicine (SMFM) recommend several time-critical steps for the initial stabilization and management of patients with AFE.⁴ However, because AFE is rare, most obstetric providers may not encounter a case for many years or even decades after they have received training, so it is unrealistic to expect that they will remember these guidelines when they are needed. For this reason, when AFE occurs, it is important to have a readily accessible cognitive aid, such as a checklist that summarizes the key management steps. The SMFM provides a checklist for initial management of AFE that can be used at your institution; it is presented in the FIGURE and provides the outline for this discussion.⁵

Provide CPR immediately

Most AFE cases are accompanied by cardiorespiratory arrest. If the patient has no pulse, call a “code” to mobilize additional help and immediately start CPR. Use a backboard to make cardiac compressions most effective and manually displace the uterus or tilt the patient to avoid supine hypotension. Designate a timekeeper to call out 1-minute intervals and record critical data, such as medication administration and laboratory orders/results.

Expedite delivery

Immediate delivery is needed if maternal cardiac activity is not restored within 4 minutes of starting CPR, with a target to have delivery completed within 5 minutes. Operative vaginal delivery may be an option if delivery is imminent, as in the case presented, but cesarean delivery (CD) will be needed in most cases. This was previously called “perimortem cesarean” delivery, but the term “resuscitative hysterotomy” has been proposed because the primary goal is to improve the effectiveness of CPR⁶ and prevent both maternal and perinatal death. CPR is less effective in pregnant women because the pregnant uterus takes a substantial fraction of the maternal cardiac output, as well as compresses the vena cava. Some experts suggest that, rather than waiting 4 minutes, CD should be started as soon as an obstetrician or other surgeon is present, unless there is an immediate response to electrical cardioversion.^6,7

In most cases, immediate CD should be performed wherever the patient is located rather than using precious minutes to move the patient to an operating room. Antiseptic preparation is expedited by simply pouring povidone-iodine or chlorhexidine over the lower abdomen if readily available; if not available, skip this step. Enter the abdomen and uterus as rapidly as possible using only a scalpel to make generous midline incisions.

If CPR is not required, proceed with cesarean or operative vaginal delivery as soon as the mother has been stabilized. These procedures should be performed using standard safety precautions outlined in the SMFM patient safety checklists for cesarean or operative vaginal delivery.^8,9

Continue to: Anticipate hemorrhage...

Be prepared for uterine atony, coagulopathy, and catastrophic hemorrhage. Initiate IV oxytocin prophylaxis as soon as the infant is delivered. Have a low threshold for giving other uterotonic agents such as methylergonovine, carboprost, or misoprostol. If hemorrhage or DIC occurs, give tranexamic acid. Have the anesthesiologist or trauma team (if available) insert an intraosseous line for fluid resuscitation if peripheral IV access is inadequate.

Massive transfusion is often needed to treat DIC, which occurs in most AFE cases. Anticipate—do not wait—for DIC to occur. We propose activating your hospital’s massive transfusion protocol (MTP) as soon as you diagnose AFE so that blood products will be available as soon as possible. A typical MTP provides several units of red blood cells, a pheresis pack of platelets, and fresh/frozen plasma (FFP). If clinically indicated, administer cryoprecipitate instead of FFP to minimize volume overload, which may occur with FFP.

CASE Part 2: MTP initiated to treat DIC

The MTP is initiated. Laboratory results immediately pre-transfusion include hemoglobin 11.3 g/dL, platelet count 46,000 per mm³, fibrinogen 87 mg/dL, and an elevated prothrombin time international normalized ratio.

Expect heart failure

The initial hemodynamic picture in AFE is right heart failure, which should optimally be managed by a specialist from anesthesiology, cardiology, or critical care as soon as they are available. An emergency department physician may manage the hemodynamics until a specialist arrives. Avoidance of fluid overload is one important principle. If fluid challenges are needed for hypovolemic shock, boluses should be restricted to 500 mL rather than the traditional 1000 mL.

Pharmacologic treatment may include vasopressors, inotropic agents, and pulmonary vasodilators. Example medications and dosages recommended by SMFM are summarized in the checklist (FIGURE).⁵

After the initial phase of recovery, the hemodynamic picture often changes from right heart failure to left heart failure. Management of left heart failure is not covered in the SMFM checklist because, by the time it appears, the patient will usually be in the intensive care unit, managed by the critical care team. Management of left heart failure generally includes diuresis as needed for cardiogenic pulmonary edema, optimization of cardiac preload, and inotropic agents or vasopressors if needed to maintain cardiac output or perfusion pressure.⁴

Debrief, learning opportunities

Complex emergencies such as AFE are rarely handled 100% perfectly, even those with a good outcome, so they present opportunities for team learning and improvement. The team should conduct a 10- to 15-minute debrief soon after the patient is stabilized. Make an explicit statement that the main goal of the debrief is to gather suggestions as to how systems and processes could be improved for next time, not to find fault or lay blame on individuals. Encourage all personnel involved in the initial management to attend and discuss what went well and what did not. Another goal is to provide support for individuals who may feel traumatized by the dramatic, frightening events surrounding an AFE and by the poor patient outcome or guarded prognosis that frequently follows. Another goal is to discuss the plan for providing support and disclosure to the patient and family.

The vast majority of AFE cases meet criteria to be designated as “sentinel events,” because of patient transfer to the intensive care unit, multi-unit blood transfusion, other severe maternal morbidities, or maternal death. Therefore, most AFE cases will trigger a root cause analysis (RCA) or other formal sentinel event analysis conducted by the hospital’s Safety or Quality Department. As with the immediate post-event debrief, the first goal of the RCA is to identify systems issues that may have resulted in suboptimal care and that can be modified to improve future care. Specific issues regarding the checklist should also be addressed:

• Was the checklist used?
• Was the checklist available?
• Are there items on the checklist that need to be modified, added, or deleted?

The RCA concludes with the development of a performance improvement plan.

Ultimately, we encourage all AFE cases be reported to the registry maintained by the Amniotic Fluid Embolism Foundation at https://www.afesupport.org/, regardless of whether the outcome was favorable for the mother and newborn. The registry includes over 130 AFE cases since 2013 from around the world. Researchers periodically report on the registry findings.¹⁰ If providers report cases with both good and bad outcomes, the registry may provide future insights regarding which adjunctive or empiric treatments may or may not be promising.

Continue to: Empiric treatments...

From time-to-time, new regimens for empiric treatment of AFE are reported. It is important to recognize that these reports are generally uncontrolled case reports of favorable outcomes and that, without a control group, it is impossible to determine to what extent the treatment contributed to the outcome or was merely incidental. Given the rarity of AFE, it seems unlikely that there will ever be a randomized clinical trial or even a controlled prospective study comparing treatment regimens.

The “A-OK” regimen is an empiric treatment that has garnered some interest after an initial case report.¹¹ It consists of an anticholinergic agent (atropine 0.2 mg IV), a selective 5-HT3 receptor antagonist (ondansetron 8 mg IV), and a nonsteroidal anti-inflammatory drug (ketorolac 15 mg IV). We have some reservations about this regimen, however, because atropine is relatively contraindicated if the patient has tachycardia (which is common in patients with hemorrhage) and ketorolac may suppress platelet function, which might be harmful for patients with DIC or thrombocytopenia.

Another empiric treatment is the “50-50-500” regimen, which includes an H1 antihistamine (diphenhydramine 50 mg IV), an H2 antihistamine (famotidine 50 mg IV), and a corticosteroid (hydrocortisone 500 mg IV). This regimen aims to suppress histamine-mediated and cell-mediated inflammatory responses, based on the notion that proinflammatory responses likely mediate much of the underlying pathophysiology of the AFE syndrome.

We would emphasize that these empiric regimens are not clinically validated, US Food and Drug Administration approved for treatment of AFE, or considered standard of care. Future reports of these and other regimens will be needed to evaluate their efficacy, limitations, and risks. Again, we encourage providers to report all AFE cases to the AFE Foundation registry, regardless of whether the treatments are successful.

CASE Conclusion

The hemorrhage stops after administration of oxytocin, carboprost, 6 units of cryoprecipitate, and a 6-unit platelet pheresis pack. The patient is transferred to the intensive care unit where she eventually requires a total of 10 units of red cells, 8 more units of cryoprecipitate, and another platelet pheresis pack. She is discharged to home in stable condition on postpartum day 4.

Be prepared, have the checklist ready

Because AFE is rare, most members of the health care team will have no prior experience managing a real case. It may have been years or decades since they had any education on AFE or they last read a review article such as this one. It is even possible the anesthesiologist, cardiologist, or critical care specialist has never heard of AFE. Thus if they rely on memory alone, there is substantial risk of forgetting items, getting dosages wrong, or other errors. With this in mind, what is the best way to prepare the team to expeditiously employ the management steps outlined here?

Use of a checklist that summarizes these key steps for early management, such as the SMFM checklist in the FIGURE, will help ensure that all relevant steps are performed in every AFE case. It is designed to be printed on a single sheet of letter-sized paper, and we propose that every labor and delivery (L&D) unit keep laminated copies of this checklist in several places where they will be immediately available should an AFE occur. Copies can be kept on the anesthesia carts in the L&D operating rooms, in an emergency procedures binder on the unit, and on the “crash carts” and hemorrhage supply carts in the L&D unit. Effective implementation of an AFE checklist requires all personnel know where to readily find it and have some familiarity with its contents.

An interdisciplinary team comprising representatives from nursing, obstetrics, and anesthesia should meet to discuss whether the checklist needs to be modified to fit the local hospital formulary or other unique local circumstances. The team should develop an implementation plan that includes where to keep checklist copies, a process to periodically ensure that the copies are still present and readable, a roll-out plan to inform all personnel about the checklist process, and most importantly a training plan that includes incorporating AFE cases into the schedule of multidisciplinary simulations and drills for obstetric emergencies. Other implementation strategies are outlined in the SMFM document.⁵

Ultimately an organized, systematic approach is recommended for management of AFE. There is no single best treatment of AFE; it is supportive and directed toward the underlying pathophysiology, which may vary from patient to patient. Therefore, although a checklist, in conjunction with regular education and simulation activities, may help optimize care and improve outcomes, there is still a high risk of maternal morbidity and mortality from AFE. ●

ILLUSTRATION BY KIMBERLY MARTENS FOR OBG MANAGEMENT

CASE Part 1: CPR initiated during induction of labor

A 32-year-old gravida 4 para 3-0-0-3 is undergoing induction of labor with intravenous (IV) oxytocin at 39 weeks of gestation. She has no significant medical or obstetric history. Fifteen minutes after reaching complete cervical dilation, she says “I don’t feel right,” then suddenly loses consciousness. The nurse finds no detectable pulse, calls a “code blue,” and initiates cardiopulmonary resuscitation (CPR). The obstetrician is notified, appears promptly, assesses the situation, and delivers a 3.6-kg baby via vacuum extraction. Apgar score is 2/10 at 1 minute and 6/10 at 5 minutes. After delivery of the placenta, there is uterine atony and brisk hemorrhage with 2 L of blood loss.

Management of AFE: A rare complication

This case demonstrates a classic presentation of amniotic fluid embolism (AFE) syndrome—a patient in labor or within 30 minutes after delivery has sudden onset of cardiorespiratory collapse followed by disseminated intravascular coagulation (DIC). AFE is rare, affecting only about 2 to 6 per 100,000 births, but classic cases have a reported maternal mortality rate that exceeds 50%.¹ It is thought to reflect a complex, systemic proinflammatory response to maternal intravasation of pregnancy material, such as trophoblast, thromboplastins, fetal cells, or amniotic fluid. Because the syndrome is not necessarily directly caused by emboli or by amniotic fluid per se,² it has been proposed that AFE be called “anaphylactoid syndrome of pregnancy,” but this terminology has not yet been widely adopted.³

Guidelines from the Society for Maternal-Fetal Medicine (SMFM) recommend several time-critical steps for the initial stabilization and management of patients with AFE.⁴ However, because AFE is rare, most obstetric providers may not encounter a case for many years or even decades after they have received training, so it is unrealistic to expect that they will remember these guidelines when they are needed. For this reason, when AFE occurs, it is important to have a readily accessible cognitive aid, such as a checklist that summarizes the key management steps. The SMFM provides a checklist for initial management of AFE that can be used at your institution; it is presented in the FIGURE and provides the outline for this discussion.⁵

Provide CPR immediately

Most AFE cases are accompanied by cardiorespiratory arrest. If the patient has no pulse, call a “code” to mobilize additional help and immediately start CPR. Use a backboard to make cardiac compressions most effective and manually displace the uterus or tilt the patient to avoid supine hypotension. Designate a timekeeper to call out 1-minute intervals and record critical data, such as medication administration and laboratory orders/results.

Expedite delivery

Immediate delivery is needed if maternal cardiac activity is not restored within 4 minutes of starting CPR, with a target to have delivery completed within 5 minutes. Operative vaginal delivery may be an option if delivery is imminent, as in the case presented, but cesarean delivery (CD) will be needed in most cases. This was previously called “perimortem cesarean” delivery, but the term “resuscitative hysterotomy” has been proposed because the primary goal is to improve the effectiveness of CPR⁶ and prevent both maternal and perinatal death. CPR is less effective in pregnant women because the pregnant uterus takes a substantial fraction of the maternal cardiac output, as well as compresses the vena cava. Some experts suggest that, rather than waiting 4 minutes, CD should be started as soon as an obstetrician or other surgeon is present, unless there is an immediate response to electrical cardioversion.^6,7

In most cases, immediate CD should be performed wherever the patient is located rather than using precious minutes to move the patient to an operating room. Antiseptic preparation is expedited by simply pouring povidone-iodine or chlorhexidine over the lower abdomen if readily available; if not available, skip this step. Enter the abdomen and uterus as rapidly as possible using only a scalpel to make generous midline incisions.

If CPR is not required, proceed with cesarean or operative vaginal delivery as soon as the mother has been stabilized. These procedures should be performed using standard safety precautions outlined in the SMFM patient safety checklists for cesarean or operative vaginal delivery.^8,9

Continue to: Anticipate hemorrhage...

Be prepared for uterine atony, coagulopathy, and catastrophic hemorrhage. Initiate IV oxytocin prophylaxis as soon as the infant is delivered. Have a low threshold for giving other uterotonic agents such as methylergonovine, carboprost, or misoprostol. If hemorrhage or DIC occurs, give tranexamic acid. Have the anesthesiologist or trauma team (if available) insert an intraosseous line for fluid resuscitation if peripheral IV access is inadequate.

Massive transfusion is often needed to treat DIC, which occurs in most AFE cases. Anticipate—do not wait—for DIC to occur. We propose activating your hospital’s massive transfusion protocol (MTP) as soon as you diagnose AFE so that blood products will be available as soon as possible. A typical MTP provides several units of red blood cells, a pheresis pack of platelets, and fresh/frozen plasma (FFP). If clinically indicated, administer cryoprecipitate instead of FFP to minimize volume overload, which may occur with FFP.

CASE Part 2: MTP initiated to treat DIC

The MTP is initiated. Laboratory results immediately pre-transfusion include hemoglobin 11.3 g/dL, platelet count 46,000 per mm³, fibrinogen 87 mg/dL, and an elevated prothrombin time international normalized ratio.

Expect heart failure

The initial hemodynamic picture in AFE is right heart failure, which should optimally be managed by a specialist from anesthesiology, cardiology, or critical care as soon as they are available. An emergency department physician may manage the hemodynamics until a specialist arrives. Avoidance of fluid overload is one important principle. If fluid challenges are needed for hypovolemic shock, boluses should be restricted to 500 mL rather than the traditional 1000 mL.

Pharmacologic treatment may include vasopressors, inotropic agents, and pulmonary vasodilators. Example medications and dosages recommended by SMFM are summarized in the checklist (FIGURE).⁵

After the initial phase of recovery, the hemodynamic picture often changes from right heart failure to left heart failure. Management of left heart failure is not covered in the SMFM checklist because, by the time it appears, the patient will usually be in the intensive care unit, managed by the critical care team. Management of left heart failure generally includes diuresis as needed for cardiogenic pulmonary edema, optimization of cardiac preload, and inotropic agents or vasopressors if needed to maintain cardiac output or perfusion pressure.⁴

Debrief, learning opportunities

Complex emergencies such as AFE are rarely handled 100% perfectly, even those with a good outcome, so they present opportunities for team learning and improvement. The team should conduct a 10- to 15-minute debrief soon after the patient is stabilized. Make an explicit statement that the main goal of the debrief is to gather suggestions as to how systems and processes could be improved for next time, not to find fault or lay blame on individuals. Encourage all personnel involved in the initial management to attend and discuss what went well and what did not. Another goal is to provide support for individuals who may feel traumatized by the dramatic, frightening events surrounding an AFE and by the poor patient outcome or guarded prognosis that frequently follows. Another goal is to discuss the plan for providing support and disclosure to the patient and family.

The vast majority of AFE cases meet criteria to be designated as “sentinel events,” because of patient transfer to the intensive care unit, multi-unit blood transfusion, other severe maternal morbidities, or maternal death. Therefore, most AFE cases will trigger a root cause analysis (RCA) or other formal sentinel event analysis conducted by the hospital’s Safety or Quality Department. As with the immediate post-event debrief, the first goal of the RCA is to identify systems issues that may have resulted in suboptimal care and that can be modified to improve future care. Specific issues regarding the checklist should also be addressed:

• Was the checklist used?
• Was the checklist available?
• Are there items on the checklist that need to be modified, added, or deleted?

The RCA concludes with the development of a performance improvement plan.

Ultimately, we encourage all AFE cases be reported to the registry maintained by the Amniotic Fluid Embolism Foundation at https://www.afesupport.org/, regardless of whether the outcome was favorable for the mother and newborn. The registry includes over 130 AFE cases since 2013 from around the world. Researchers periodically report on the registry findings.¹⁰ If providers report cases with both good and bad outcomes, the registry may provide future insights regarding which adjunctive or empiric treatments may or may not be promising.

Continue to: Empiric treatments...

From time-to-time, new regimens for empiric treatment of AFE are reported. It is important to recognize that these reports are generally uncontrolled case reports of favorable outcomes and that, without a control group, it is impossible to determine to what extent the treatment contributed to the outcome or was merely incidental. Given the rarity of AFE, it seems unlikely that there will ever be a randomized clinical trial or even a controlled prospective study comparing treatment regimens.

The “A-OK” regimen is an empiric treatment that has garnered some interest after an initial case report.¹¹ It consists of an anticholinergic agent (atropine 0.2 mg IV), a selective 5-HT3 receptor antagonist (ondansetron 8 mg IV), and a nonsteroidal anti-inflammatory drug (ketorolac 15 mg IV). We have some reservations about this regimen, however, because atropine is relatively contraindicated if the patient has tachycardia (which is common in patients with hemorrhage) and ketorolac may suppress platelet function, which might be harmful for patients with DIC or thrombocytopenia.

Another empiric treatment is the “50-50-500” regimen, which includes an H1 antihistamine (diphenhydramine 50 mg IV), an H2 antihistamine (famotidine 50 mg IV), and a corticosteroid (hydrocortisone 500 mg IV). This regimen aims to suppress histamine-mediated and cell-mediated inflammatory responses, based on the notion that proinflammatory responses likely mediate much of the underlying pathophysiology of the AFE syndrome.

We would emphasize that these empiric regimens are not clinically validated, US Food and Drug Administration approved for treatment of AFE, or considered standard of care. Future reports of these and other regimens will be needed to evaluate their efficacy, limitations, and risks. Again, we encourage providers to report all AFE cases to the AFE Foundation registry, regardless of whether the treatments are successful.

CASE Conclusion

The hemorrhage stops after administration of oxytocin, carboprost, 6 units of cryoprecipitate, and a 6-unit platelet pheresis pack. The patient is transferred to the intensive care unit where she eventually requires a total of 10 units of red cells, 8 more units of cryoprecipitate, and another platelet pheresis pack. She is discharged to home in stable condition on postpartum day 4.

Be prepared, have the checklist ready

Because AFE is rare, most members of the health care team will have no prior experience managing a real case. It may have been years or decades since they had any education on AFE or they last read a review article such as this one. It is even possible the anesthesiologist, cardiologist, or critical care specialist has never heard of AFE. Thus if they rely on memory alone, there is substantial risk of forgetting items, getting dosages wrong, or other errors. With this in mind, what is the best way to prepare the team to expeditiously employ the management steps outlined here?

Use of a checklist that summarizes these key steps for early management, such as the SMFM checklist in the FIGURE, will help ensure that all relevant steps are performed in every AFE case. It is designed to be printed on a single sheet of letter-sized paper, and we propose that every labor and delivery (L&D) unit keep laminated copies of this checklist in several places where they will be immediately available should an AFE occur. Copies can be kept on the anesthesia carts in the L&D operating rooms, in an emergency procedures binder on the unit, and on the “crash carts” and hemorrhage supply carts in the L&D unit. Effective implementation of an AFE checklist requires all personnel know where to readily find it and have some familiarity with its contents.

An interdisciplinary team comprising representatives from nursing, obstetrics, and anesthesia should meet to discuss whether the checklist needs to be modified to fit the local hospital formulary or other unique local circumstances. The team should develop an implementation plan that includes where to keep checklist copies, a process to periodically ensure that the copies are still present and readable, a roll-out plan to inform all personnel about the checklist process, and most importantly a training plan that includes incorporating AFE cases into the schedule of multidisciplinary simulations and drills for obstetric emergencies. Other implementation strategies are outlined in the SMFM document.⁵

Ultimately an organized, systematic approach is recommended for management of AFE. There is no single best treatment of AFE; it is supportive and directed toward the underlying pathophysiology, which may vary from patient to patient. Therefore, although a checklist, in conjunction with regular education and simulation activities, may help optimize care and improve outcomes, there is still a high risk of maternal morbidity and mortality from AFE. ●

ILLUSTRATION BY KIMBERLY MARTENS FOR OBG MANAGEMENT

CASE Part 1: CPR initiated during induction of labor

A 32-year-old gravida 4 para 3-0-0-3 is undergoing induction of labor with intravenous (IV) oxytocin at 39 weeks of gestation. She has no significant medical or obstetric history. Fifteen minutes after reaching complete cervical dilation, she says “I don’t feel right,” then suddenly loses consciousness. The nurse finds no detectable pulse, calls a “code blue,” and initiates cardiopulmonary resuscitation (CPR). The obstetrician is notified, appears promptly, assesses the situation, and delivers a 3.6-kg baby via vacuum extraction. Apgar score is 2/10 at 1 minute and 6/10 at 5 minutes. After delivery of the placenta, there is uterine atony and brisk hemorrhage with 2 L of blood loss.

Management of AFE: A rare complication

This case demonstrates a classic presentation of amniotic fluid embolism (AFE) syndrome—a patient in labor or within 30 minutes after delivery has sudden onset of cardiorespiratory collapse followed by disseminated intravascular coagulation (DIC). AFE is rare, affecting only about 2 to 6 per 100,000 births, but classic cases have a reported maternal mortality rate that exceeds 50%.¹ It is thought to reflect a complex, systemic proinflammatory response to maternal intravasation of pregnancy material, such as trophoblast, thromboplastins, fetal cells, or amniotic fluid. Because the syndrome is not necessarily directly caused by emboli or by amniotic fluid per se,² it has been proposed that AFE be called “anaphylactoid syndrome of pregnancy,” but this terminology has not yet been widely adopted.³

Guidelines from the Society for Maternal-Fetal Medicine (SMFM) recommend several time-critical steps for the initial stabilization and management of patients with AFE.⁴ However, because AFE is rare, most obstetric providers may not encounter a case for many years or even decades after they have received training, so it is unrealistic to expect that they will remember these guidelines when they are needed. For this reason, when AFE occurs, it is important to have a readily accessible cognitive aid, such as a checklist that summarizes the key management steps. The SMFM provides a checklist for initial management of AFE that can be used at your institution; it is presented in the FIGURE and provides the outline for this discussion.⁵

Provide CPR immediately

Most AFE cases are accompanied by cardiorespiratory arrest. If the patient has no pulse, call a “code” to mobilize additional help and immediately start CPR. Use a backboard to make cardiac compressions most effective and manually displace the uterus or tilt the patient to avoid supine hypotension. Designate a timekeeper to call out 1-minute intervals and record critical data, such as medication administration and laboratory orders/results.

Expedite delivery

Immediate delivery is needed if maternal cardiac activity is not restored within 4 minutes of starting CPR, with a target to have delivery completed within 5 minutes. Operative vaginal delivery may be an option if delivery is imminent, as in the case presented, but cesarean delivery (CD) will be needed in most cases. This was previously called “perimortem cesarean” delivery, but the term “resuscitative hysterotomy” has been proposed because the primary goal is to improve the effectiveness of CPR⁶ and prevent both maternal and perinatal death. CPR is less effective in pregnant women because the pregnant uterus takes a substantial fraction of the maternal cardiac output, as well as compresses the vena cava. Some experts suggest that, rather than waiting 4 minutes, CD should be started as soon as an obstetrician or other surgeon is present, unless there is an immediate response to electrical cardioversion.^6,7

In most cases, immediate CD should be performed wherever the patient is located rather than using precious minutes to move the patient to an operating room. Antiseptic preparation is expedited by simply pouring povidone-iodine or chlorhexidine over the lower abdomen if readily available; if not available, skip this step. Enter the abdomen and uterus as rapidly as possible using only a scalpel to make generous midline incisions.

If CPR is not required, proceed with cesarean or operative vaginal delivery as soon as the mother has been stabilized. These procedures should be performed using standard safety precautions outlined in the SMFM patient safety checklists for cesarean or operative vaginal delivery.^8,9

Continue to: Anticipate hemorrhage...

Be prepared for uterine atony, coagulopathy, and catastrophic hemorrhage. Initiate IV oxytocin prophylaxis as soon as the infant is delivered. Have a low threshold for giving other uterotonic agents such as methylergonovine, carboprost, or misoprostol. If hemorrhage or DIC occurs, give tranexamic acid. Have the anesthesiologist or trauma team (if available) insert an intraosseous line for fluid resuscitation if peripheral IV access is inadequate.

Massive transfusion is often needed to treat DIC, which occurs in most AFE cases. Anticipate—do not wait—for DIC to occur. We propose activating your hospital’s massive transfusion protocol (MTP) as soon as you diagnose AFE so that blood products will be available as soon as possible. A typical MTP provides several units of red blood cells, a pheresis pack of platelets, and fresh/frozen plasma (FFP). If clinically indicated, administer cryoprecipitate instead of FFP to minimize volume overload, which may occur with FFP.

CASE Part 2: MTP initiated to treat DIC

The MTP is initiated. Laboratory results immediately pre-transfusion include hemoglobin 11.3 g/dL, platelet count 46,000 per mm³, fibrinogen 87 mg/dL, and an elevated prothrombin time international normalized ratio.

Expect heart failure

The initial hemodynamic picture in AFE is right heart failure, which should optimally be managed by a specialist from anesthesiology, cardiology, or critical care as soon as they are available. An emergency department physician may manage the hemodynamics until a specialist arrives. Avoidance of fluid overload is one important principle. If fluid challenges are needed for hypovolemic shock, boluses should be restricted to 500 mL rather than the traditional 1000 mL.

Pharmacologic treatment may include vasopressors, inotropic agents, and pulmonary vasodilators. Example medications and dosages recommended by SMFM are summarized in the checklist (FIGURE).⁵

After the initial phase of recovery, the hemodynamic picture often changes from right heart failure to left heart failure. Management of left heart failure is not covered in the SMFM checklist because, by the time it appears, the patient will usually be in the intensive care unit, managed by the critical care team. Management of left heart failure generally includes diuresis as needed for cardiogenic pulmonary edema, optimization of cardiac preload, and inotropic agents or vasopressors if needed to maintain cardiac output or perfusion pressure.⁴

Debrief, learning opportunities

Complex emergencies such as AFE are rarely handled 100% perfectly, even those with a good outcome, so they present opportunities for team learning and improvement. The team should conduct a 10- to 15-minute debrief soon after the patient is stabilized. Make an explicit statement that the main goal of the debrief is to gather suggestions as to how systems and processes could be improved for next time, not to find fault or lay blame on individuals. Encourage all personnel involved in the initial management to attend and discuss what went well and what did not. Another goal is to provide support for individuals who may feel traumatized by the dramatic, frightening events surrounding an AFE and by the poor patient outcome or guarded prognosis that frequently follows. Another goal is to discuss the plan for providing support and disclosure to the patient and family.

The vast majority of AFE cases meet criteria to be designated as “sentinel events,” because of patient transfer to the intensive care unit, multi-unit blood transfusion, other severe maternal morbidities, or maternal death. Therefore, most AFE cases will trigger a root cause analysis (RCA) or other formal sentinel event analysis conducted by the hospital’s Safety or Quality Department. As with the immediate post-event debrief, the first goal of the RCA is to identify systems issues that may have resulted in suboptimal care and that can be modified to improve future care. Specific issues regarding the checklist should also be addressed:

• Was the checklist used?
• Was the checklist available?
• Are there items on the checklist that need to be modified, added, or deleted?

The RCA concludes with the development of a performance improvement plan.

Ultimately, we encourage all AFE cases be reported to the registry maintained by the Amniotic Fluid Embolism Foundation at https://www.afesupport.org/, regardless of whether the outcome was favorable for the mother and newborn. The registry includes over 130 AFE cases since 2013 from around the world. Researchers periodically report on the registry findings.¹⁰ If providers report cases with both good and bad outcomes, the registry may provide future insights regarding which adjunctive or empiric treatments may or may not be promising.

Continue to: Empiric treatments...

From time-to-time, new regimens for empiric treatment of AFE are reported. It is important to recognize that these reports are generally uncontrolled case reports of favorable outcomes and that, without a control group, it is impossible to determine to what extent the treatment contributed to the outcome or was merely incidental. Given the rarity of AFE, it seems unlikely that there will ever be a randomized clinical trial or even a controlled prospective study comparing treatment regimens.

The “A-OK” regimen is an empiric treatment that has garnered some interest after an initial case report.¹¹ It consists of an anticholinergic agent (atropine 0.2 mg IV), a selective 5-HT3 receptor antagonist (ondansetron 8 mg IV), and a nonsteroidal anti-inflammatory drug (ketorolac 15 mg IV). We have some reservations about this regimen, however, because atropine is relatively contraindicated if the patient has tachycardia (which is common in patients with hemorrhage) and ketorolac may suppress platelet function, which might be harmful for patients with DIC or thrombocytopenia.

Another empiric treatment is the “50-50-500” regimen, which includes an H1 antihistamine (diphenhydramine 50 mg IV), an H2 antihistamine (famotidine 50 mg IV), and a corticosteroid (hydrocortisone 500 mg IV). This regimen aims to suppress histamine-mediated and cell-mediated inflammatory responses, based on the notion that proinflammatory responses likely mediate much of the underlying pathophysiology of the AFE syndrome.

We would emphasize that these empiric regimens are not clinically validated, US Food and Drug Administration approved for treatment of AFE, or considered standard of care. Future reports of these and other regimens will be needed to evaluate their efficacy, limitations, and risks. Again, we encourage providers to report all AFE cases to the AFE Foundation registry, regardless of whether the treatments are successful.

CASE Conclusion

The hemorrhage stops after administration of oxytocin, carboprost, 6 units of cryoprecipitate, and a 6-unit platelet pheresis pack. The patient is transferred to the intensive care unit where she eventually requires a total of 10 units of red cells, 8 more units of cryoprecipitate, and another platelet pheresis pack. She is discharged to home in stable condition on postpartum day 4.

Be prepared, have the checklist ready

Because AFE is rare, most members of the health care team will have no prior experience managing a real case. It may have been years or decades since they had any education on AFE or they last read a review article such as this one. It is even possible the anesthesiologist, cardiologist, or critical care specialist has never heard of AFE. Thus if they rely on memory alone, there is substantial risk of forgetting items, getting dosages wrong, or other errors. With this in mind, what is the best way to prepare the team to expeditiously employ the management steps outlined here?

Use of a checklist that summarizes these key steps for early management, such as the SMFM checklist in the FIGURE, will help ensure that all relevant steps are performed in every AFE case. It is designed to be printed on a single sheet of letter-sized paper, and we propose that every labor and delivery (L&D) unit keep laminated copies of this checklist in several places where they will be immediately available should an AFE occur. Copies can be kept on the anesthesia carts in the L&D operating rooms, in an emergency procedures binder on the unit, and on the “crash carts” and hemorrhage supply carts in the L&D unit. Effective implementation of an AFE checklist requires all personnel know where to readily find it and have some familiarity with its contents.

An interdisciplinary team comprising representatives from nursing, obstetrics, and anesthesia should meet to discuss whether the checklist needs to be modified to fit the local hospital formulary or other unique local circumstances. The team should develop an implementation plan that includes where to keep checklist copies, a process to periodically ensure that the copies are still present and readable, a roll-out plan to inform all personnel about the checklist process, and most importantly a training plan that includes incorporating AFE cases into the schedule of multidisciplinary simulations and drills for obstetric emergencies. Other implementation strategies are outlined in the SMFM document.⁵

Ultimately an organized, systematic approach is recommended for management of AFE. There is no single best treatment of AFE; it is supportive and directed toward the underlying pathophysiology, which may vary from patient to patient. Therefore, although a checklist, in conjunction with regular education and simulation activities, may help optimize care and improve outcomes, there is still a high risk of maternal morbidity and mortality from AFE. ●