Obstetrics

Female physicians often spend their child-bearing years in medical training and developing their careers, and this can create problems.  

In a survey of just over 1,000 female oncologists, 95% said their career plans were at least somewhat associated with the timing of when to start a family.

The most striking finding was that one third of respondents had miscarried and another one third reported difficulty with infertility that required fertility counseling and/or treatment.

One third reported experiencing discrimination during pregnancy, and another third said they experienced discrimination for taking maternity leave, and having more than one child increased the likelihood of this.

The most common negative factor associated with family planning was long work hours and heavy workload (66.6%),

These findings suggest there are systemic changes needed not only in the healthcare setting but in society as a whole around women in the workplace and their choices of childbearing, say the authors.

The study was published online in JAMA Network Open and led by Anna Lee MD, MPH, from the department of radiation oncology, University of Texas MD Anderson Cancer Center, Houston. 

In an invited commentary, Mona Saleh, MD, and Stephanie Blank, MD, from the department of obstetrics, gynecology, and reproductive science at the Icahn School of Medicine at Mount Sinai in New York, suggest that cultural changes are needed that go beyond women in medicine.

“These cultural values are so deeply pervasive (one could also say invasive) that they affect even these most educated and wealthy professional women, such as those who participated in this survey,” the editorialists write.

“[The researchers] advocate for early education on assisted reproductive technology (ART) risks, benefits, and success rates, but this is not getting at the underlying issue: Pregnancy discrimination and unfair distribution of childbearing responsibilities are a reflection of a larger problematic culture rather than an issue specific to women in medicine,” they add.
 

Survey details

The survey comprised a novel 39-item questionnaire distributed to 1,004 U.S. female oncologists from May 7 to June 30, 2020, via email and social media channels.

Most respondents (84.4%) were married, and 71% were currently working full-time.

About one-third (35%) worked in radiation oncology, another third (34.3%) in medical oncology, 18.4% in surgical oncology, and 9.1% in pediatric oncology.

A total of 768 respondents (76.5%) had children, and of these, 415 (41.3%) first gave birth during postgraduate training and 275 (27.4%) gave birth in years 1-5 as an attending physician.

Of all respondents who had been pregnant, approximately two-thirds (65.7%) had some type of pregnancy complication. About one-third of respondents (31.7%) reported having experienced a miscarriage after a confirmed pregnancy; of those, 61.6% reported one miscarriage, while the remainder had two or more miscarriages (38.4%).

Approximately one-third (31.4%) of respondents reported difficulty with infertility that required fertility counseling and/or treatment.

The questionnaire also asked about assisted reproductive technology, and 164 participants (16.3%) reported the use of fertility medications, and 53 (5.3%) reported cryopreservation of eggs. Nearly 13% reported the use of intrauterine insemination and 13.2% reported the use of in vivo fertilization. Among those who experienced fertility concerns, 36.6% (232 of 634) reported facing financial burdens because of fertility or pregnancy that was in some way associated with their career choice.

When asked on the survey if fertility preservation should be discussed with women during medical school and/or residency, 65.7% of respondents stated that it should.

However, the editorialists suggest that “encouraging formal and directed education regarding the infertility risks specifically toward female physicians (which Lee et al. recommend) could be perceived as a blanket recommendation that it is best for women in medicine to delay childbearing and pursue ART.”

“Medical schools and residency and fellowship training programs should instead focus their energy on creating a framework and culture that normalizes conception during these points in training while also subsidizing and supporting trainees and physicians who prefer to use ART and delay fertility until after training,” they suggest.

The editorialists also emphasized that women may choose to become pregnant at any point during the years that it takes to go from being a medical student to resident/fellow to attending physician, and they should be supported by their workplace on their decisions.

The study was funded by grants from National Institutes of Health/National Cancer Institute Cancer Center.

Dr. Lee and coauthors reported no relevant financial relationships. Dr. Blank reported receiving grants from AstraZeneca, Aravive, Akesobio, GlaxoSmithKline, Merck, and Seattle Genetics outside the submitted work. Dr. Saleh reports no relevant financial relationships.

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

Female physicians often spend their child-bearing years in medical training and developing their careers, and this can create problems.  

In a survey of just over 1,000 female oncologists, 95% said their career plans were at least somewhat associated with the timing of when to start a family.

The most striking finding was that one third of respondents had miscarried and another one third reported difficulty with infertility that required fertility counseling and/or treatment.

One third reported experiencing discrimination during pregnancy, and another third said they experienced discrimination for taking maternity leave, and having more than one child increased the likelihood of this.

The most common negative factor associated with family planning was long work hours and heavy workload (66.6%),

These findings suggest there are systemic changes needed not only in the healthcare setting but in society as a whole around women in the workplace and their choices of childbearing, say the authors.

The study was published online in JAMA Network Open and led by Anna Lee MD, MPH, from the department of radiation oncology, University of Texas MD Anderson Cancer Center, Houston. 

In an invited commentary, Mona Saleh, MD, and Stephanie Blank, MD, from the department of obstetrics, gynecology, and reproductive science at the Icahn School of Medicine at Mount Sinai in New York, suggest that cultural changes are needed that go beyond women in medicine.

“These cultural values are so deeply pervasive (one could also say invasive) that they affect even these most educated and wealthy professional women, such as those who participated in this survey,” the editorialists write.

“[The researchers] advocate for early education on assisted reproductive technology (ART) risks, benefits, and success rates, but this is not getting at the underlying issue: Pregnancy discrimination and unfair distribution of childbearing responsibilities are a reflection of a larger problematic culture rather than an issue specific to women in medicine,” they add.
 

Survey details

The survey comprised a novel 39-item questionnaire distributed to 1,004 U.S. female oncologists from May 7 to June 30, 2020, via email and social media channels.

Most respondents (84.4%) were married, and 71% were currently working full-time.

About one-third (35%) worked in radiation oncology, another third (34.3%) in medical oncology, 18.4% in surgical oncology, and 9.1% in pediatric oncology.

A total of 768 respondents (76.5%) had children, and of these, 415 (41.3%) first gave birth during postgraduate training and 275 (27.4%) gave birth in years 1-5 as an attending physician.

Of all respondents who had been pregnant, approximately two-thirds (65.7%) had some type of pregnancy complication. About one-third of respondents (31.7%) reported having experienced a miscarriage after a confirmed pregnancy; of those, 61.6% reported one miscarriage, while the remainder had two or more miscarriages (38.4%).

Approximately one-third (31.4%) of respondents reported difficulty with infertility that required fertility counseling and/or treatment.

The questionnaire also asked about assisted reproductive technology, and 164 participants (16.3%) reported the use of fertility medications, and 53 (5.3%) reported cryopreservation of eggs. Nearly 13% reported the use of intrauterine insemination and 13.2% reported the use of in vivo fertilization. Among those who experienced fertility concerns, 36.6% (232 of 634) reported facing financial burdens because of fertility or pregnancy that was in some way associated with their career choice.

When asked on the survey if fertility preservation should be discussed with women during medical school and/or residency, 65.7% of respondents stated that it should.

However, the editorialists suggest that “encouraging formal and directed education regarding the infertility risks specifically toward female physicians (which Lee et al. recommend) could be perceived as a blanket recommendation that it is best for women in medicine to delay childbearing and pursue ART.”

“Medical schools and residency and fellowship training programs should instead focus their energy on creating a framework and culture that normalizes conception during these points in training while also subsidizing and supporting trainees and physicians who prefer to use ART and delay fertility until after training,” they suggest.

The editorialists also emphasized that women may choose to become pregnant at any point during the years that it takes to go from being a medical student to resident/fellow to attending physician, and they should be supported by their workplace on their decisions.

The study was funded by grants from National Institutes of Health/National Cancer Institute Cancer Center.

Dr. Lee and coauthors reported no relevant financial relationships. Dr. Blank reported receiving grants from AstraZeneca, Aravive, Akesobio, GlaxoSmithKline, Merck, and Seattle Genetics outside the submitted work. Dr. Saleh reports no relevant financial relationships.

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

Female physicians often spend their child-bearing years in medical training and developing their careers, and this can create problems.  

In a survey of just over 1,000 female oncologists, 95% said their career plans were at least somewhat associated with the timing of when to start a family.

The most striking finding was that one third of respondents had miscarried and another one third reported difficulty with infertility that required fertility counseling and/or treatment.

One third reported experiencing discrimination during pregnancy, and another third said they experienced discrimination for taking maternity leave, and having more than one child increased the likelihood of this.

The most common negative factor associated with family planning was long work hours and heavy workload (66.6%),

These findings suggest there are systemic changes needed not only in the healthcare setting but in society as a whole around women in the workplace and their choices of childbearing, say the authors.

The study was published online in JAMA Network Open and led by Anna Lee MD, MPH, from the department of radiation oncology, University of Texas MD Anderson Cancer Center, Houston. 

In an invited commentary, Mona Saleh, MD, and Stephanie Blank, MD, from the department of obstetrics, gynecology, and reproductive science at the Icahn School of Medicine at Mount Sinai in New York, suggest that cultural changes are needed that go beyond women in medicine.

“These cultural values are so deeply pervasive (one could also say invasive) that they affect even these most educated and wealthy professional women, such as those who participated in this survey,” the editorialists write.

“[The researchers] advocate for early education on assisted reproductive technology (ART) risks, benefits, and success rates, but this is not getting at the underlying issue: Pregnancy discrimination and unfair distribution of childbearing responsibilities are a reflection of a larger problematic culture rather than an issue specific to women in medicine,” they add.
 

Survey details

The survey comprised a novel 39-item questionnaire distributed to 1,004 U.S. female oncologists from May 7 to June 30, 2020, via email and social media channels.

Most respondents (84.4%) were married, and 71% were currently working full-time.

About one-third (35%) worked in radiation oncology, another third (34.3%) in medical oncology, 18.4% in surgical oncology, and 9.1% in pediatric oncology.

A total of 768 respondents (76.5%) had children, and of these, 415 (41.3%) first gave birth during postgraduate training and 275 (27.4%) gave birth in years 1-5 as an attending physician.

Of all respondents who had been pregnant, approximately two-thirds (65.7%) had some type of pregnancy complication. About one-third of respondents (31.7%) reported having experienced a miscarriage after a confirmed pregnancy; of those, 61.6% reported one miscarriage, while the remainder had two or more miscarriages (38.4%).

Approximately one-third (31.4%) of respondents reported difficulty with infertility that required fertility counseling and/or treatment.

The questionnaire also asked about assisted reproductive technology, and 164 participants (16.3%) reported the use of fertility medications, and 53 (5.3%) reported cryopreservation of eggs. Nearly 13% reported the use of intrauterine insemination and 13.2% reported the use of in vivo fertilization. Among those who experienced fertility concerns, 36.6% (232 of 634) reported facing financial burdens because of fertility or pregnancy that was in some way associated with their career choice.

When asked on the survey if fertility preservation should be discussed with women during medical school and/or residency, 65.7% of respondents stated that it should.

However, the editorialists suggest that “encouraging formal and directed education regarding the infertility risks specifically toward female physicians (which Lee et al. recommend) could be perceived as a blanket recommendation that it is best for women in medicine to delay childbearing and pursue ART.”

“Medical schools and residency and fellowship training programs should instead focus their energy on creating a framework and culture that normalizes conception during these points in training while also subsidizing and supporting trainees and physicians who prefer to use ART and delay fertility until after training,” they suggest.

The editorialists also emphasized that women may choose to become pregnant at any point during the years that it takes to go from being a medical student to resident/fellow to attending physician, and they should be supported by their workplace on their decisions.

The study was funded by grants from National Institutes of Health/National Cancer Institute Cancer Center.

Dr. Lee and coauthors reported no relevant financial relationships. Dr. Blank reported receiving grants from AstraZeneca, Aravive, Akesobio, GlaxoSmithKline, Merck, and Seattle Genetics outside the submitted work. Dr. Saleh reports no relevant financial relationships.

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

Women who experience preeclampsia during pregnancy are almost twice as likely to have a heart attack or stroke within 20 years of giving birth as pregnant women who did not, according to a new study published in the European Journal of Preventive Cardiology. The risks are especially high in the first decade after giving birth, the researchers found.
 

Preeclampsia is the onset of high blood pressure after the 20th week of pregnancy combined with signs of organ damage, such as excess protein in the urine. It can occur in up to 8% of pregnancies, and the association between preeclampsia and long-term cardiac risks is well-known. But new research suggests these risks appear much earlier in life than expected – as early as age 30 – at a time when women are often not screened for signs of heart trouble

“Targeted interventions cannot wait until women with preeclampsia become eligible for conventional screening programs in middle age,” Sara Hallum, PhD, a coauthor of the study, told this news organization.

Dr. Hallum, who was an epidemiologist at the University of Copenhagen at the time of the study, and colleagues evaluated the medical histories of more than 1.1 million women in Denmark who became pregnant once or twice between 1978 and 2017. Of this group, 3% had experienced preeclampsia. They compared rates of heart attack and stroke between the two groups over time.

While 1.2% of the entire study population had experienced a heart attack or stroke within 20 years of giving birth, 2% of the women with a history of preeclampsia had such an event. Within the first decade after delivery, women with a history of preeclampsia were four times as likely to have a heart attack and three times as likely to have a stroke as other women.

Women aged 30-39 with a history of preeclampsia were nearly five times as likely to have a heart attack and three times as likely to have a stroke as similar-aged women. And if a woman gave birth twice and had preeclampsia only during the second pregnancy, she was at especially high risk for a heart attack, the researchers found.

“Women with a history of preeclampsia should be monitored routinely for modifiable risk factors, particularly for increased blood pressure,” Dr. Hallum said.

The Danish study population is racially homogeneous, so the researchers were not able to distinguish the effects of preeclampsia by racial group. In the United States, strong evidence shows that Black women experience the effects of preeclampsia more than others.
 

A useful clue to cardiac risk

Ellen Seely, MD, an endocrinologist at Brigham and Women’s Hospital in Boston, who specializes in preeclampsia, said physicians are less likely to ask women who have been pregnant if they had experienced preeclampsia than to ask if they smoke or have a family history of heart attacks. As a result, they may miss a looming cardiovascular event, especially in younger women who appear healthy.

“Emerging high blood pressure shouldn’t be ignored” in a seemingly healthy young woman, Dr. Seely said, particularly if that woman has divulged a history of preeclampsia. The doctor’s first step should be to verify hypertension, Dr. Seely said. If high blood pressure is evident, immediate treatment – such as encouraging more physical activity and a healthier diet – should follow. Watchful waiting in such cases is inappropriate, she added.

Although the experience of having preeclampsia is unpleasant and scary, Dr. Seely noted that in at least one way it can prove advantageous. Some women who did not experience preeclampsia will end up having a heart attack, sometimes with no prior warning that anything was amiss. At least a history of preeclampsia provides a clue that women should take care of their hearts.

“The patient carries their history with them wherever they go,” Dr. Seely said. For now, this reality often requires women to mention their pregnancy history even if a provider doesn’t ask. Someday, Dr. Seely said, asking about that history will become just as routine for providers as asking about family history.

The study was funded by the Danish Heart Foundation. Dr. Hallum and Dr. Seely have reported no relevant financial relationships.

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

Women who experience preeclampsia during pregnancy are almost twice as likely to have a heart attack or stroke within 20 years of giving birth as pregnant women who did not, according to a new study published in the European Journal of Preventive Cardiology. The risks are especially high in the first decade after giving birth, the researchers found.
 

Preeclampsia is the onset of high blood pressure after the 20th week of pregnancy combined with signs of organ damage, such as excess protein in the urine. It can occur in up to 8% of pregnancies, and the association between preeclampsia and long-term cardiac risks is well-known. But new research suggests these risks appear much earlier in life than expected – as early as age 30 – at a time when women are often not screened for signs of heart trouble

“Targeted interventions cannot wait until women with preeclampsia become eligible for conventional screening programs in middle age,” Sara Hallum, PhD, a coauthor of the study, told this news organization.

Dr. Hallum, who was an epidemiologist at the University of Copenhagen at the time of the study, and colleagues evaluated the medical histories of more than 1.1 million women in Denmark who became pregnant once or twice between 1978 and 2017. Of this group, 3% had experienced preeclampsia. They compared rates of heart attack and stroke between the two groups over time.

While 1.2% of the entire study population had experienced a heart attack or stroke within 20 years of giving birth, 2% of the women with a history of preeclampsia had such an event. Within the first decade after delivery, women with a history of preeclampsia were four times as likely to have a heart attack and three times as likely to have a stroke as other women.

Women aged 30-39 with a history of preeclampsia were nearly five times as likely to have a heart attack and three times as likely to have a stroke as similar-aged women. And if a woman gave birth twice and had preeclampsia only during the second pregnancy, she was at especially high risk for a heart attack, the researchers found.

“Women with a history of preeclampsia should be monitored routinely for modifiable risk factors, particularly for increased blood pressure,” Dr. Hallum said.

The Danish study population is racially homogeneous, so the researchers were not able to distinguish the effects of preeclampsia by racial group. In the United States, strong evidence shows that Black women experience the effects of preeclampsia more than others.
 

A useful clue to cardiac risk

Ellen Seely, MD, an endocrinologist at Brigham and Women’s Hospital in Boston, who specializes in preeclampsia, said physicians are less likely to ask women who have been pregnant if they had experienced preeclampsia than to ask if they smoke or have a family history of heart attacks. As a result, they may miss a looming cardiovascular event, especially in younger women who appear healthy.

“Emerging high blood pressure shouldn’t be ignored” in a seemingly healthy young woman, Dr. Seely said, particularly if that woman has divulged a history of preeclampsia. The doctor’s first step should be to verify hypertension, Dr. Seely said. If high blood pressure is evident, immediate treatment – such as encouraging more physical activity and a healthier diet – should follow. Watchful waiting in such cases is inappropriate, she added.

Although the experience of having preeclampsia is unpleasant and scary, Dr. Seely noted that in at least one way it can prove advantageous. Some women who did not experience preeclampsia will end up having a heart attack, sometimes with no prior warning that anything was amiss. At least a history of preeclampsia provides a clue that women should take care of their hearts.

“The patient carries their history with them wherever they go,” Dr. Seely said. For now, this reality often requires women to mention their pregnancy history even if a provider doesn’t ask. Someday, Dr. Seely said, asking about that history will become just as routine for providers as asking about family history.

The study was funded by the Danish Heart Foundation. Dr. Hallum and Dr. Seely have reported no relevant financial relationships.

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

Women who experience preeclampsia during pregnancy are almost twice as likely to have a heart attack or stroke within 20 years of giving birth as pregnant women who did not, according to a new study published in the European Journal of Preventive Cardiology. The risks are especially high in the first decade after giving birth, the researchers found.
 

Preeclampsia is the onset of high blood pressure after the 20th week of pregnancy combined with signs of organ damage, such as excess protein in the urine. It can occur in up to 8% of pregnancies, and the association between preeclampsia and long-term cardiac risks is well-known. But new research suggests these risks appear much earlier in life than expected – as early as age 30 – at a time when women are often not screened for signs of heart trouble

“Targeted interventions cannot wait until women with preeclampsia become eligible for conventional screening programs in middle age,” Sara Hallum, PhD, a coauthor of the study, told this news organization.

Dr. Hallum, who was an epidemiologist at the University of Copenhagen at the time of the study, and colleagues evaluated the medical histories of more than 1.1 million women in Denmark who became pregnant once or twice between 1978 and 2017. Of this group, 3% had experienced preeclampsia. They compared rates of heart attack and stroke between the two groups over time.

While 1.2% of the entire study population had experienced a heart attack or stroke within 20 years of giving birth, 2% of the women with a history of preeclampsia had such an event. Within the first decade after delivery, women with a history of preeclampsia were four times as likely to have a heart attack and three times as likely to have a stroke as other women.

Women aged 30-39 with a history of preeclampsia were nearly five times as likely to have a heart attack and three times as likely to have a stroke as similar-aged women. And if a woman gave birth twice and had preeclampsia only during the second pregnancy, she was at especially high risk for a heart attack, the researchers found.

“Women with a history of preeclampsia should be monitored routinely for modifiable risk factors, particularly for increased blood pressure,” Dr. Hallum said.

The Danish study population is racially homogeneous, so the researchers were not able to distinguish the effects of preeclampsia by racial group. In the United States, strong evidence shows that Black women experience the effects of preeclampsia more than others.
 

A useful clue to cardiac risk

Ellen Seely, MD, an endocrinologist at Brigham and Women’s Hospital in Boston, who specializes in preeclampsia, said physicians are less likely to ask women who have been pregnant if they had experienced preeclampsia than to ask if they smoke or have a family history of heart attacks. As a result, they may miss a looming cardiovascular event, especially in younger women who appear healthy.

“Emerging high blood pressure shouldn’t be ignored” in a seemingly healthy young woman, Dr. Seely said, particularly if that woman has divulged a history of preeclampsia. The doctor’s first step should be to verify hypertension, Dr. Seely said. If high blood pressure is evident, immediate treatment – such as encouraging more physical activity and a healthier diet – should follow. Watchful waiting in such cases is inappropriate, she added.

Although the experience of having preeclampsia is unpleasant and scary, Dr. Seely noted that in at least one way it can prove advantageous. Some women who did not experience preeclampsia will end up having a heart attack, sometimes with no prior warning that anything was amiss. At least a history of preeclampsia provides a clue that women should take care of their hearts.

“The patient carries their history with them wherever they go,” Dr. Seely said. For now, this reality often requires women to mention their pregnancy history even if a provider doesn’t ask. Someday, Dr. Seely said, asking about that history will become just as routine for providers as asking about family history.

The study was funded by the Danish Heart Foundation. Dr. Hallum and Dr. Seely have reported no relevant financial relationships.

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

The risk of health harms from alcohol is low for people who consume two standard drinks or fewer per week, but it’s higher with greater consumption, according to new guidance from the Canadian Centre on Substance Use and Addiction.

“Drinking less is better,” says the guidance, which replaces Canada’s 2011 Low-Risk Drinking Guidelines (LRDGs).

Developed in consultation with an executive committee from federal, provincial, and territorial governments; national organizations; three scientific expert panels; and an internal evidence review working group, the guidance presents the following findings:

• Consuming no drinks per week has benefits, such as better health and better sleep, and it’s the only safe option during pregnancy.
• Consuming one or two standard drinks weekly will likely not have alcohol-related consequences.
• Three to six drinks raise the risk of developing breast, colon, and other cancers.
• Seven or more increase the risk of heart disease or stroke.
• Each additional drink “radically increases” the risk of these health consequences.

“Alcohol is more harmful than was previously thought and is a key component of the health of your patients,” Adam Sherk, PhD, a scientist at the Canadian Institute for Substance Use Research at the University of Victoria (B.C.), and a member of the scientific expert panel that contributed to the guidance, said in an interview. “Display and discuss the new guidance with your patients with the main message that drinking less is better.”

Peter Butt, MD, a clinical associate professor at the University of Saskatchewan, Saskatoon, and cochair of the guidance project, said in an interview: “The World Health Organization has identified over 200 ICD-coded conditions associated with alcohol use. This creates many opportunities to inquire into quantity and frequency of alcohol use, relate it to the patient’s health and well-being, and provide advice on reduction.”

“Canada’s Guidance on Alcohol and Health: Final Report” and a related infographic were published online Jan. 17.
 

Continuum of risk

The impetus for the new guidance came from the fact that “our 2011 LRDGs were no longer current, and there was emerging evidence that people drinking within those levels were coming to harm,” said Dr. Butt.

That evidence indicates that alcohol causes at least seven types of cancer, mostly of the breast or colon; is a risk factor for most types of heart disease; and is a main cause of liver disease. Evidence also indicates that avoiding drinking to the point of intoxication will reduce people’s risk of perpetrating alcohol-related violence.

Responding to the need to accurately quantify the risk, the guidance defines a “standard” drink as 12 oz of beer, cooler, or cider (5% alcohol); 5 oz of wine (12% alcohol); and 1.5 oz of spirits such as whiskey, vodka, or gin (40% alcohol).

Using different mortality risk thresholds, the project’s experts developed the following continuum of risk:

• Low for individuals who consume two standard drinks or fewer per week
• Moderate for those who consume from three to six standard drinks per week
• Increasingly high for those who consume seven standard drinks or more per week

The guidance makes the following observations:

• Consuming more than two standard drinks per drinking occasion is associated with an increased risk of harms to self and others, including injuries and violence.
• When pregnant or trying to get pregnant, no amount of alcohol is safe.
• When breastfeeding, not drinking is safest.
• Above the upper limit of the moderate risk zone, health risks increase more steeply for females than males.
• Far more injuries, violence, and deaths result from men’s alcohol use, especially for per occasion drinking, than from women’s alcohol use.
• Young people should delay alcohol use for as long as possible.
• Individuals should not start to use alcohol or increase their alcohol use for health benefits.
• Any reduction in alcohol use is beneficial.

Other national guidelines

“Countries that haven’t updated their alcohol use guidelines recently should do so, as the evidence regarding alcohol and health has advanced considerably in the past 10 years,” said Dr. Sherk. He acknowledged that “any time health guidance changes substantially, it’s reasonable to expect a period of readjustment.”

“Some will be resistant,” Dr. Butt agreed. “Some professionals will need more education than others on the health effects of alcohol. Some patients will also be more invested in drinking than others. The harm-reduction, risk-zone approach should assist in the process of engaging patients and helping them reduce over time.

“Just as we benefited from the updates done in the United Kingdom, France, and especially Australia, so also researchers elsewhere will critique our work and our approach and make their own decisions on how best to communicate with their public,” Dr. Butt said. He noted that Canada’s contributions regarding the association between alcohol and violence, as well as their sex/gender approach to the evidence, “may influence the next country’s review.”

Commenting on whether the United States should consider changing its guidance, Timothy Brennan, MD, MPH, chief of clinical services for the Addiction Institute of Mount Sinai Health System in New York, said in an interview, “A lot of people will be surprised at the recommended limits on alcohol. Most think that they can have one or two glasses of alcohol per day and not have any increased risk to their health. I think the Canadians deserve credit for putting themselves out there.”

Dr. Brennan said there will “certainly be pushback by the drinking lobby, which is very strong both in the U.S. and in Canada.” In fact, the national trade group Beer Canada was recently quoted as stating that it still supports the 2011 guidelines and that the updating process lacked full transparency and expert technical peer review.

Nevertheless, Dr. Brennan said, “it’s overwhelmingly clear that alcohol affects a ton of different parts of our body, so limiting the amount of alcohol we take in is always going to be a good thing. The Canadian graphic is great because it color-codes the risk. I recommend that clinicians put it up in their offices and begin quantifying the units of alcohol that are going into a patient’s body each day.”

A version of this article originally appeared on Medscape.com.

The risk of health harms from alcohol is low for people who consume two standard drinks or fewer per week, but it’s higher with greater consumption, according to new guidance from the Canadian Centre on Substance Use and Addiction.

“Drinking less is better,” says the guidance, which replaces Canada’s 2011 Low-Risk Drinking Guidelines (LRDGs).

Developed in consultation with an executive committee from federal, provincial, and territorial governments; national organizations; three scientific expert panels; and an internal evidence review working group, the guidance presents the following findings:

• Consuming no drinks per week has benefits, such as better health and better sleep, and it’s the only safe option during pregnancy.
• Consuming one or two standard drinks weekly will likely not have alcohol-related consequences.
• Three to six drinks raise the risk of developing breast, colon, and other cancers.
• Seven or more increase the risk of heart disease or stroke.
• Each additional drink “radically increases” the risk of these health consequences.

“Alcohol is more harmful than was previously thought and is a key component of the health of your patients,” Adam Sherk, PhD, a scientist at the Canadian Institute for Substance Use Research at the University of Victoria (B.C.), and a member of the scientific expert panel that contributed to the guidance, said in an interview. “Display and discuss the new guidance with your patients with the main message that drinking less is better.”

Peter Butt, MD, a clinical associate professor at the University of Saskatchewan, Saskatoon, and cochair of the guidance project, said in an interview: “The World Health Organization has identified over 200 ICD-coded conditions associated with alcohol use. This creates many opportunities to inquire into quantity and frequency of alcohol use, relate it to the patient’s health and well-being, and provide advice on reduction.”

“Canada’s Guidance on Alcohol and Health: Final Report” and a related infographic were published online Jan. 17.
 

Continuum of risk

The impetus for the new guidance came from the fact that “our 2011 LRDGs were no longer current, and there was emerging evidence that people drinking within those levels were coming to harm,” said Dr. Butt.

That evidence indicates that alcohol causes at least seven types of cancer, mostly of the breast or colon; is a risk factor for most types of heart disease; and is a main cause of liver disease. Evidence also indicates that avoiding drinking to the point of intoxication will reduce people’s risk of perpetrating alcohol-related violence.

Responding to the need to accurately quantify the risk, the guidance defines a “standard” drink as 12 oz of beer, cooler, or cider (5% alcohol); 5 oz of wine (12% alcohol); and 1.5 oz of spirits such as whiskey, vodka, or gin (40% alcohol).

Using different mortality risk thresholds, the project’s experts developed the following continuum of risk:

• Low for individuals who consume two standard drinks or fewer per week
• Moderate for those who consume from three to six standard drinks per week
• Increasingly high for those who consume seven standard drinks or more per week

The guidance makes the following observations:

• Consuming more than two standard drinks per drinking occasion is associated with an increased risk of harms to self and others, including injuries and violence.
• When pregnant or trying to get pregnant, no amount of alcohol is safe.
• When breastfeeding, not drinking is safest.
• Above the upper limit of the moderate risk zone, health risks increase more steeply for females than males.
• Far more injuries, violence, and deaths result from men’s alcohol use, especially for per occasion drinking, than from women’s alcohol use.
• Young people should delay alcohol use for as long as possible.
• Individuals should not start to use alcohol or increase their alcohol use for health benefits.
• Any reduction in alcohol use is beneficial.

Other national guidelines

“Countries that haven’t updated their alcohol use guidelines recently should do so, as the evidence regarding alcohol and health has advanced considerably in the past 10 years,” said Dr. Sherk. He acknowledged that “any time health guidance changes substantially, it’s reasonable to expect a period of readjustment.”

“Some will be resistant,” Dr. Butt agreed. “Some professionals will need more education than others on the health effects of alcohol. Some patients will also be more invested in drinking than others. The harm-reduction, risk-zone approach should assist in the process of engaging patients and helping them reduce over time.

“Just as we benefited from the updates done in the United Kingdom, France, and especially Australia, so also researchers elsewhere will critique our work and our approach and make their own decisions on how best to communicate with their public,” Dr. Butt said. He noted that Canada’s contributions regarding the association between alcohol and violence, as well as their sex/gender approach to the evidence, “may influence the next country’s review.”

Commenting on whether the United States should consider changing its guidance, Timothy Brennan, MD, MPH, chief of clinical services for the Addiction Institute of Mount Sinai Health System in New York, said in an interview, “A lot of people will be surprised at the recommended limits on alcohol. Most think that they can have one or two glasses of alcohol per day and not have any increased risk to their health. I think the Canadians deserve credit for putting themselves out there.”

Dr. Brennan said there will “certainly be pushback by the drinking lobby, which is very strong both in the U.S. and in Canada.” In fact, the national trade group Beer Canada was recently quoted as stating that it still supports the 2011 guidelines and that the updating process lacked full transparency and expert technical peer review.

Nevertheless, Dr. Brennan said, “it’s overwhelmingly clear that alcohol affects a ton of different parts of our body, so limiting the amount of alcohol we take in is always going to be a good thing. The Canadian graphic is great because it color-codes the risk. I recommend that clinicians put it up in their offices and begin quantifying the units of alcohol that are going into a patient’s body each day.”

A version of this article originally appeared on Medscape.com.

The risk of health harms from alcohol is low for people who consume two standard drinks or fewer per week, but it’s higher with greater consumption, according to new guidance from the Canadian Centre on Substance Use and Addiction.

“Drinking less is better,” says the guidance, which replaces Canada’s 2011 Low-Risk Drinking Guidelines (LRDGs).

Developed in consultation with an executive committee from federal, provincial, and territorial governments; national organizations; three scientific expert panels; and an internal evidence review working group, the guidance presents the following findings:

• Consuming no drinks per week has benefits, such as better health and better sleep, and it’s the only safe option during pregnancy.
• Consuming one or two standard drinks weekly will likely not have alcohol-related consequences.
• Three to six drinks raise the risk of developing breast, colon, and other cancers.
• Seven or more increase the risk of heart disease or stroke.
• Each additional drink “radically increases” the risk of these health consequences.

“Alcohol is more harmful than was previously thought and is a key component of the health of your patients,” Adam Sherk, PhD, a scientist at the Canadian Institute for Substance Use Research at the University of Victoria (B.C.), and a member of the scientific expert panel that contributed to the guidance, said in an interview. “Display and discuss the new guidance with your patients with the main message that drinking less is better.”

Peter Butt, MD, a clinical associate professor at the University of Saskatchewan, Saskatoon, and cochair of the guidance project, said in an interview: “The World Health Organization has identified over 200 ICD-coded conditions associated with alcohol use. This creates many opportunities to inquire into quantity and frequency of alcohol use, relate it to the patient’s health and well-being, and provide advice on reduction.”

“Canada’s Guidance on Alcohol and Health: Final Report” and a related infographic were published online Jan. 17.
 

Continuum of risk

The impetus for the new guidance came from the fact that “our 2011 LRDGs were no longer current, and there was emerging evidence that people drinking within those levels were coming to harm,” said Dr. Butt.

That evidence indicates that alcohol causes at least seven types of cancer, mostly of the breast or colon; is a risk factor for most types of heart disease; and is a main cause of liver disease. Evidence also indicates that avoiding drinking to the point of intoxication will reduce people’s risk of perpetrating alcohol-related violence.

Responding to the need to accurately quantify the risk, the guidance defines a “standard” drink as 12 oz of beer, cooler, or cider (5% alcohol); 5 oz of wine (12% alcohol); and 1.5 oz of spirits such as whiskey, vodka, or gin (40% alcohol).

Using different mortality risk thresholds, the project’s experts developed the following continuum of risk:

• Low for individuals who consume two standard drinks or fewer per week
• Moderate for those who consume from three to six standard drinks per week
• Increasingly high for those who consume seven standard drinks or more per week

The guidance makes the following observations:

• Consuming more than two standard drinks per drinking occasion is associated with an increased risk of harms to self and others, including injuries and violence.
• When pregnant or trying to get pregnant, no amount of alcohol is safe.
• When breastfeeding, not drinking is safest.
• Above the upper limit of the moderate risk zone, health risks increase more steeply for females than males.
• Far more injuries, violence, and deaths result from men’s alcohol use, especially for per occasion drinking, than from women’s alcohol use.
• Young people should delay alcohol use for as long as possible.
• Individuals should not start to use alcohol or increase their alcohol use for health benefits.
• Any reduction in alcohol use is beneficial.

Other national guidelines

“Countries that haven’t updated their alcohol use guidelines recently should do so, as the evidence regarding alcohol and health has advanced considerably in the past 10 years,” said Dr. Sherk. He acknowledged that “any time health guidance changes substantially, it’s reasonable to expect a period of readjustment.”

“Some will be resistant,” Dr. Butt agreed. “Some professionals will need more education than others on the health effects of alcohol. Some patients will also be more invested in drinking than others. The harm-reduction, risk-zone approach should assist in the process of engaging patients and helping them reduce over time.

“Just as we benefited from the updates done in the United Kingdom, France, and especially Australia, so also researchers elsewhere will critique our work and our approach and make their own decisions on how best to communicate with their public,” Dr. Butt said. He noted that Canada’s contributions regarding the association between alcohol and violence, as well as their sex/gender approach to the evidence, “may influence the next country’s review.”

Commenting on whether the United States should consider changing its guidance, Timothy Brennan, MD, MPH, chief of clinical services for the Addiction Institute of Mount Sinai Health System in New York, said in an interview, “A lot of people will be surprised at the recommended limits on alcohol. Most think that they can have one or two glasses of alcohol per day and not have any increased risk to their health. I think the Canadians deserve credit for putting themselves out there.”

Dr. Brennan said there will “certainly be pushback by the drinking lobby, which is very strong both in the U.S. and in Canada.” In fact, the national trade group Beer Canada was recently quoted as stating that it still supports the 2011 guidelines and that the updating process lacked full transparency and expert technical peer review.

Nevertheless, Dr. Brennan said, “it’s overwhelmingly clear that alcohol affects a ton of different parts of our body, so limiting the amount of alcohol we take in is always going to be a good thing. The Canadian graphic is great because it color-codes the risk. I recommend that clinicians put it up in their offices and begin quantifying the units of alcohol that are going into a patient’s body each day.”

A version of this article originally appeared on Medscape.com.

Thadhani R, Lemoine E, Rana S, et al. Circulating angiogenic factor levels in hypertensive disorders of pregnancy. N Engl J Med. 2022;1. DOI: 10.1056/EVIDoa2200161

EXPERT COMMENTARY
 

The standard core lecture on preeclampsia given to all medical students frequently begins with an epic, if not potentially apocryphal, statement regarding how this disease has been noted in the annals of medical history since the time of the Ancients. Although contemporary diagnostic criteria for preeclampsia are not that far out of date, they are close. The increased urinary protein loss and hypertension preceding eclamptic seizures was first noted at the end of the 19th century. The blood pressure and proteinuria criteria used for diagnosis was codified in its contemporary form in the late 1940s. Since then, “tweak” rather than “overhaul” probably best describes the updates of the obstetrical community to the definition of preeclampsia. This has just changed.

Details of the study

Thadhani and colleagues prospectively recruited a nationally representative observational cohort of patients hospitalized for hypertension during pregnancy, then followed the patients until either the diagnosis of preeclampsia with severe features or for 2 weeks, whichever came first. At enrollment, circulating levels of the soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF) were measured. In a 2-phased design, the first 219 participants were used to define a sFlt-1/PlGF ratio that would predict progression to severe preeclampsia within 2 weeks. The next 556 enrollees served to validate the predictive properties of the ratio. The authors found that a sFlt-1/PlGF ratio of ≥40 predicted progression to preeclampsia with severe features with an area under the curve (AUC) of 0.92.

As products of the trophoblasts, both sFlt-1 and PlGF have been mooted for almost 2 decades as potential predictive, if not diagnostic, aids with respect to preeclampsia. Indeed, both analytes are commercially available in Europe for specifically this purpose and many maternal-fetal medicine practitioners working in the European equivalent American tertiary referral centers use an sFlt-1/PlGF ratio as their primary criteria for a diagnosis of preeclampsia. Within the United States, there was an initial flurry of interest in and an infusion of corporate and federal research support for sFlt-1 and PlGF as diagnostic aids for preeclampsia in the mid-2000s. However, at present, the US Food and Drug Administration (FDA) has not sanctioned these (or any) biomarkers to aid in the diagnosis of preeclampsia. As Thermo-Fisher Scientific (Waltham, Massachusetts) is a supporting partner in this study, it is almost certain that these data will be submitted for review by the FDA as part of an application for a preeclampsia diagnostic. At some point in the near future, American practitioners will potentially be able to join their European colleagues in utilizing these biomarkers in the diagnosis of preeclampsia with severe features. ●

Thadhani R, Lemoine E, Rana S, et al. Circulating angiogenic factor levels in hypertensive disorders of pregnancy. N Engl J Med. 2022;1. DOI: 10.1056/EVIDoa2200161

EXPERT COMMENTARY
 

The standard core lecture on preeclampsia given to all medical students frequently begins with an epic, if not potentially apocryphal, statement regarding how this disease has been noted in the annals of medical history since the time of the Ancients. Although contemporary diagnostic criteria for preeclampsia are not that far out of date, they are close. The increased urinary protein loss and hypertension preceding eclamptic seizures was first noted at the end of the 19th century. The blood pressure and proteinuria criteria used for diagnosis was codified in its contemporary form in the late 1940s. Since then, “tweak” rather than “overhaul” probably best describes the updates of the obstetrical community to the definition of preeclampsia. This has just changed.

Details of the study

Thadhani and colleagues prospectively recruited a nationally representative observational cohort of patients hospitalized for hypertension during pregnancy, then followed the patients until either the diagnosis of preeclampsia with severe features or for 2 weeks, whichever came first. At enrollment, circulating levels of the soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF) were measured. In a 2-phased design, the first 219 participants were used to define a sFlt-1/PlGF ratio that would predict progression to severe preeclampsia within 2 weeks. The next 556 enrollees served to validate the predictive properties of the ratio. The authors found that a sFlt-1/PlGF ratio of ≥40 predicted progression to preeclampsia with severe features with an area under the curve (AUC) of 0.92.

As products of the trophoblasts, both sFlt-1 and PlGF have been mooted for almost 2 decades as potential predictive, if not diagnostic, aids with respect to preeclampsia. Indeed, both analytes are commercially available in Europe for specifically this purpose and many maternal-fetal medicine practitioners working in the European equivalent American tertiary referral centers use an sFlt-1/PlGF ratio as their primary criteria for a diagnosis of preeclampsia. Within the United States, there was an initial flurry of interest in and an infusion of corporate and federal research support for sFlt-1 and PlGF as diagnostic aids for preeclampsia in the mid-2000s. However, at present, the US Food and Drug Administration (FDA) has not sanctioned these (or any) biomarkers to aid in the diagnosis of preeclampsia. As Thermo-Fisher Scientific (Waltham, Massachusetts) is a supporting partner in this study, it is almost certain that these data will be submitted for review by the FDA as part of an application for a preeclampsia diagnostic. At some point in the near future, American practitioners will potentially be able to join their European colleagues in utilizing these biomarkers in the diagnosis of preeclampsia with severe features. ●

Thadhani R, Lemoine E, Rana S, et al. Circulating angiogenic factor levels in hypertensive disorders of pregnancy. N Engl J Med. 2022;1. DOI: 10.1056/EVIDoa2200161

EXPERT COMMENTARY
 

The standard core lecture on preeclampsia given to all medical students frequently begins with an epic, if not potentially apocryphal, statement regarding how this disease has been noted in the annals of medical history since the time of the Ancients. Although contemporary diagnostic criteria for preeclampsia are not that far out of date, they are close. The increased urinary protein loss and hypertension preceding eclamptic seizures was first noted at the end of the 19th century. The blood pressure and proteinuria criteria used for diagnosis was codified in its contemporary form in the late 1940s. Since then, “tweak” rather than “overhaul” probably best describes the updates of the obstetrical community to the definition of preeclampsia. This has just changed.

Details of the study

Thadhani and colleagues prospectively recruited a nationally representative observational cohort of patients hospitalized for hypertension during pregnancy, then followed the patients until either the diagnosis of preeclampsia with severe features or for 2 weeks, whichever came first. At enrollment, circulating levels of the soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF) were measured. In a 2-phased design, the first 219 participants were used to define a sFlt-1/PlGF ratio that would predict progression to severe preeclampsia within 2 weeks. The next 556 enrollees served to validate the predictive properties of the ratio. The authors found that a sFlt-1/PlGF ratio of ≥40 predicted progression to preeclampsia with severe features with an area under the curve (AUC) of 0.92.

As products of the trophoblasts, both sFlt-1 and PlGF have been mooted for almost 2 decades as potential predictive, if not diagnostic, aids with respect to preeclampsia. Indeed, both analytes are commercially available in Europe for specifically this purpose and many maternal-fetal medicine practitioners working in the European equivalent American tertiary referral centers use an sFlt-1/PlGF ratio as their primary criteria for a diagnosis of preeclampsia. Within the United States, there was an initial flurry of interest in and an infusion of corporate and federal research support for sFlt-1 and PlGF as diagnostic aids for preeclampsia in the mid-2000s. However, at present, the US Food and Drug Administration (FDA) has not sanctioned these (or any) biomarkers to aid in the diagnosis of preeclampsia. As Thermo-Fisher Scientific (Waltham, Massachusetts) is a supporting partner in this study, it is almost certain that these data will be submitted for review by the FDA as part of an application for a preeclampsia diagnostic. At some point in the near future, American practitioners will potentially be able to join their European colleagues in utilizing these biomarkers in the diagnosis of preeclampsia with severe features. ●

In the musical Hamilton, there is a line from the song “The Election of 1800” in which, after a tumultuous time, Thomas Jefferson pleads for a sense of normalcy with, “Can we get back to politics?”

Trying to get back to “normal,” whatever that is, characterized the year 2022. Peeking out from under the constant shadow of the COVID-19 pandemic (not really gone, definitely not forgotten) were some blockbuster obstetrical headlines, including those on the CHAP (Chronic Hypertension and Pregnancy) trial and the impact of the Dobbs v Jackson Supreme Court decision. As these have been extensively covered in both OBG Management and other publications, in this Update we simply ask, “Can we get back to obstetrics?” as we focus on some straightforward patient care guidelines.

Thus, we offer updated information on the use of progesterone for preterm birth prevention, management of pregnancies that result from in vitro fertilization (IVF), and headache management in pregnant and postpartum patients.

Society guidance and FDA  advisement on the use of  progesterone for the prevention  of spontaneous preterm birth

American College of Obstetricians and Gynecologists’ Committee on Practice Bulletins–Obstetrics. Prediction and prevention of spontaneous preterm birth. ACOG practice bulletin no. 234. Obstet Gynecol. 2021;138:e65-e90.

EPPPIC Group. Evaluating Progestogens for Preventing Preterm birth International Collaborative (EPPPIC): meta-analysis of individual participant data from randomised controlled trials. Lancet. 2021;397:1183-1194.

This is not déjà vu! Progesterone and spontaneous preterm birth (sPTB) is a hot topic again. If you wonder what to tell your patients, you are not alone. Preterm birth (PTB) continues to pose a challenge in obstetrics, with a most recently reported overall rate of 10.49%¹ in the United States—a 4% increase from 2019. Preterm birth accounts for approximately 75% of perinatal mortality and more than half of neonatal morbidity.²

What has not changed

A recent practice bulletin from the American College of Obstetricians and Gynecologists (ACOG) notes that some risk factors and screening assessments for PTB remain unchanged, including²:

• A history of PTB increases the risk for subsequent PTB. Risk increases with the number of prior preterm deliveries.
• A short cervix (<25 mm between 16 and  24 weeks’ gestation) is a risk factor for sPTB.
• The cervix should be visualized during the anatomy ultrasound exam (18 0/7 to 22 6/7 weeks’ gestation) in all pregnant patients regardless of prior birth history. If the cervix length (CL) appears shortened on transabdominal imaging, transvaginal (TV) imaging should be performed.
• Patients with a current singleton pregnancy and history of sPTB should have serial TV cervical measurements between 16 0/7 and 24 0/7 weeks’ gestation.²

EPPPIC changes and key takeaway points

In a meta-analysis of data from 31 randomized controlled trials, the EPPPIC (Evaluating Progestogens for Preventing Preterm birth International Collaborative) investigators compared vaginal progesterone, intramuscular 17-hydroxyprogesterone caproate  (17-OHPC), or oral progesterone with control or with each other in women at risk for PTB.³ Outcomes included PTB and the associated adverse neonatal and maternal outcomes.

The EPPPIC study’s main findings were:

• Singleton pregnancies at high risk for PTB due to prior sPTB or short cervix who received 17-OHPC or vaginal progesterone were less likely to deliver before  34 weeks’ gestation compared with those who received no treatment.
• There is a benefit to both 17-OHPC and vaginal progesterone in reducing the risk of PTB, with no clear evidence to support one intervention’s effectiveness over the other.
• There is benefit to either 17-OHPC or vaginal progesterone for CL less than 25 mm. The shorter the CL, the greater the absolute risk reduction on PTB.
• In multifetal pregnancies, use of 17-OHPC, when compared with placebo, was shown to increase the risk of preterm premature rupture of membranes. Neither 17-OHPC nor vaginal progesterone was found to reduce the risk of sPTB in multifetal pregnancies.³

What continues to change

While the March 30, 2021, statement from the Society for Maternal-Fetal Medicine (SMFM), “Response to EPPPIC and consideration for the use of progestogens for the prevention of preterm birth” (https://www .smfm.org/publications/383-smfm-stat ement-response-to-epppic-and-consider ations-of-the-use-of-progestogens-for-the -prevention-of-preterm-birth), stands, ACOG has withdrawn its accompanying Practice Advisory on guidance for integrating the EPPPIC findings.

In August 2022, the US Food and Drug Administration (FDA) granted a hearing on the Center for Drug Evaluation and Research’s proposal to withdraw approval for Makena (hydroxyprogesterone caproate injection, 250 mg/mL, once weekly) on the basis that available evidence does not demonstrate that it is effective for its approved indication to reduce the risk of PTB in women with a singleton pregnancy with a history of singleton sPTB.⁴

The key takeaway points from the FDA hearing (October 17–19, 2022) were:

• A better designed randomized controlled confirmatory trial is needed in the most at-risk patients to determine if Makena is effective for its approved indication.
• Makena and its approved generic equivalents remain on the market until the FDA makes its final decision regarding approval.⁴

Continue to: Managing pregnancies that result from IVF...

Society for Maternal-Fetal Medicine (SMFM); Ghidini A, Gandhi M, McCoy J, et al; Publications Committee. Society for Maternal-Fetal Medicine consult series #60: management of pregnancies resulting from in vitro fertilization. Am J Obstet Gynecol. 2022;226:B2-B12.

Assisted reproductive technology contributes to 1.6% of all infant births, and although most pregnancies are uncomplicated, some specific risks alter management.^5–7 For example, IVF is associated with increased rates of prematurity and its complications, fetal growth restriction, low birth weight, congenital anomalies, genetic abnormalities, and placental abnormalities. In addition, there is doubling of the risk of morbidities to the pregnant IVF patient, including but not limited to hypertensive disorders and diabetes. These complications are thought to be related to both the process of IVF itself as well as to conditions that contribute to subfertility and infertility in the first place.

Genetic screening and diagnostic testing options

IVF pregnancies have a documented increase in chromosomal abnormalities compared with spontaneously conceived pregnancies due to the following factors:

• karyotypic abnormalities in couples with infertility
• microdeletions on the Y chromosome in patients with oligospermia or azoospermia
• de novo chromosomal abnormalities in IVF pregnancies that utilize intracytoplasmic sperm injection (ICSI)
• fragile X mutations in patients with reduced ovarian reserve
• imprinting disorders in patients with fertility issues.

A common misconception is that preimplantation genetic testing renders prenatal genetic screening or testing unnecessary. However, preimplantation testing can be anywhere from 43% to 84% concordant with prenatal diagnostic testing due to biologic and technical factors. Therefore, all pregnancies should be offered the same options of aneuploidy screening as well as diagnostic testing. Pretest counseling should include an increased risk in IVF pregnancies of false-positives for the first-trimester screen and “no-call” results for cell-free fetal DNA. Additionally, diagnostic testing is recommended specifically in cases where mosaic embryos are transferred when euploid embryos are not available.

Counseling on fetal reduction for multifetal pregnancies

The risks of multifetal pregnancies (particularly higher order multiples) are significant and well documented for both the patient and the fetuses. It is therefore recommended that the option of multifetal pregnancy reduction be discussed, including the risks and benefits of reduction versus pregnancy continuation, timing, procedural considerations, and genetic testing options.^5,8

Detailed anatomic survey and fetal echocardiogram are indicated

Fetal anomalies, including congenital cardiac defects, occur at a higher rate in IVF pregnancies compared with spontaneously conceived pregnancies (475/10,000 live births vs 317/10,000 live births). Placental anomalies (such as placenta previa, vasa previa, and velamentous cord insertion) are also more common in this population. A detailed anatomic survey is therefore recommended for all IVF pregnancies and it is suggested that a fetal echocardiogram is offered these patients as well.

Pregnancy management and delivery considerations

Despite an increased risk of preterm birth, preeclampsia, and fetal growth restriction in IVF pregnancies (odds ratios range, 1.4–2), serial cervical lengths, serial growth ultrasound exams, and low-dose aspirin are not recommended for the sole indication of IVF. Due to lack of data on the utility of serial exams, a single screening cervical length at the time of anatomic survey and a third-trimester growth assessment are recommended. For aspirin, IVF qualifies as a “moderate” risk factor for preeclampsia; it is therefore recommended if another moderate risk factor is present (for example, nulliparity, obesity, or family history of preeclampsia).⁹

There is a 2- to 3-fold increased risk of stillbirth in IVF pregnancies; therefore, antenatal surveillance in the third trimester is recommended (weekly starting at 36 weeks for the sole indication of IVF).¹⁰ As no specific studies have evaluated the timing of delivery in IVF pregnancies, delivery recommendations include the option of 39-week delivery with shared decision-making with the patient.

Continue to: Evaluating and treating headaches in pregnancy and postpartum...

Evaluating and treating headaches in pregnancy and postpartum

American College of Obstetricians and Gynecologists. Clinical practice guideline no. 3: headaches in pregnancy and postpartum. Obstet Gynecol. 2022;139:944-972.

For obstetricians, headaches are a common and often frustrating condition to treat, as many of the available diagnostic tools and medications are either not recommended or have no data on use in pregnancy and lactation. Additionally, a headache is not always just a headache but could be a sign of a time-sensitive serious complication. An updated guideline from the American College of Obstetricians and Gynecologists approaches the topic of headaches in a stepwise algorithm that promotes efficiency and efficacy in diagnosis  and treatment.¹¹

Types of headaches

The primary headache types—migraine, cluster, and tension—are distinguished from each other by patient characteristics, quality, duration, location, and related symptoms. Reassuringly, headache frequency decreases by 30% to 80% during pregnancy, which allows for the option to decrease, change, or stop current medications, ideally prior to pregnancy. Prevention via use of calcium channel blockers, antihistamines, or β-blockers is recommended, as requiring acute treatments more than 2 days per week increases the risk of medication overuse headaches.

Treating acute headache

For patients who present with an acute headache consistent with their usual type, treatment starts with known medications that are compatible with pregnancy and proceeds in a stepwise fashion:

1. Acetaminophen 1,000 mg orally with or without caffeine 130 mg orally (maximum dose, acetaminophen < 3.25–4 g per day, caffeine 200 mg per day)

2. Metoclopramide 10 mg intravenously with or without diphenhydramine 25 mg intravenously (for nausea and to counteract restlessness and offer sedation)

3. If headache continues after steps 1 and 2, consider the following secondary treatment options: magnesium sulfate 1–2 g intravenously, sumatriptan 6 mg subcutaneously or 20-mg nasal spray, ibuprofen 600 mg orally once, or ketorolac 30 mg intravenously once (second trimester only)

4. If continued treatment and/or hospitalization is required after step 3, steroids can be used: prednisone 20 mg 4 times a day for 2 days or methylprednisolone 4-mg dose pack over 6 days

5. Do not use butalbital, opioids, or ergotamines due to lack of efficacy in providing additional pain relief, potential for addiction, risk of medication overuse headaches, and association with fetal/ pregnancy abnormalities.

Consider secondary headache

An acute headache discordant from the patient’s usual type or with concerning symptoms (“red flags”) requires consideration of secondary headaches as well as a comprehensive symptom evaluation, imaging, and consultation as needed. While secondary headaches postpartum are most likely musculoskeletal in nature, the following symptoms need to be evaluated immediately:

• rapid onset/change from baseline
• “thunderclap” nature
• hypertension
• fever
• focal neurologic deficits (blurry vision or blindness, confusion, seizures)
• altered consciousness
• laboratory abnormalities.

The differential diagnosis includes preeclampsia, reversible cerebral vasoconstriction syndrome (RCVS), posterior reversible encephalopathy syndrome (PRES), infection, cerebral venous sinus thrombosis (CVST), post–dural puncture (PDP) headache, idiopathic intracranial hypertension (IIH), and less likely, carotid dissection, subarachnoid hemorrhage, intracranial hemorrhage, pituitary apoplexy, or neoplasm.

Treatment. Individualized treatment depends on the diagnosis. Preeclampsia with severe features is treated with antihypertensive medication, magnesium sulfate, and delivery planning. PDP headache is treated with epidural blood patch, sphenopalatine block, or occipital block with an anesthesiology consultation. If preeclampsia and PDP are ruled out, or if there are more concerning neurologic features, imaging is essential, as 25% of pregnant patients with acute headaches will have a secondary etiology. Magnetic resonance imaging without contrast is preferred due to concerns about gadolinium crossing the placenta and the lack of data on long-term accumulation in fetal  tissues. Once diagnosed on imaging, PRES and RCVS are treated with antihypertensives and delivery. CVST is treated with anticoagulation and a thrombophilia workup. IIH may be treated with acetazolamide after 20 weeks or serial lumbar punctures. Intracranial vascular abnormalities may be treated with endoscopic resection and steroids. ●

In the musical Hamilton, there is a line from the song “The Election of 1800” in which, after a tumultuous time, Thomas Jefferson pleads for a sense of normalcy with, “Can we get back to politics?”

Trying to get back to “normal,” whatever that is, characterized the year 2022. Peeking out from under the constant shadow of the COVID-19 pandemic (not really gone, definitely not forgotten) were some blockbuster obstetrical headlines, including those on the CHAP (Chronic Hypertension and Pregnancy) trial and the impact of the Dobbs v Jackson Supreme Court decision. As these have been extensively covered in both OBG Management and other publications, in this Update we simply ask, “Can we get back to obstetrics?” as we focus on some straightforward patient care guidelines.

Thus, we offer updated information on the use of progesterone for preterm birth prevention, management of pregnancies that result from in vitro fertilization (IVF), and headache management in pregnant and postpartum patients.

Society guidance and FDA  advisement on the use of  progesterone for the prevention  of spontaneous preterm birth

American College of Obstetricians and Gynecologists’ Committee on Practice Bulletins–Obstetrics. Prediction and prevention of spontaneous preterm birth. ACOG practice bulletin no. 234. Obstet Gynecol. 2021;138:e65-e90.

EPPPIC Group. Evaluating Progestogens for Preventing Preterm birth International Collaborative (EPPPIC): meta-analysis of individual participant data from randomised controlled trials. Lancet. 2021;397:1183-1194.

This is not déjà vu! Progesterone and spontaneous preterm birth (sPTB) is a hot topic again. If you wonder what to tell your patients, you are not alone. Preterm birth (PTB) continues to pose a challenge in obstetrics, with a most recently reported overall rate of 10.49%¹ in the United States—a 4% increase from 2019. Preterm birth accounts for approximately 75% of perinatal mortality and more than half of neonatal morbidity.²

What has not changed

A recent practice bulletin from the American College of Obstetricians and Gynecologists (ACOG) notes that some risk factors and screening assessments for PTB remain unchanged, including²:

• A history of PTB increases the risk for subsequent PTB. Risk increases with the number of prior preterm deliveries.
• A short cervix (<25 mm between 16 and  24 weeks’ gestation) is a risk factor for sPTB.
• The cervix should be visualized during the anatomy ultrasound exam (18 0/7 to 22 6/7 weeks’ gestation) in all pregnant patients regardless of prior birth history. If the cervix length (CL) appears shortened on transabdominal imaging, transvaginal (TV) imaging should be performed.
• Patients with a current singleton pregnancy and history of sPTB should have serial TV cervical measurements between 16 0/7 and 24 0/7 weeks’ gestation.²

EPPPIC changes and key takeaway points

In a meta-analysis of data from 31 randomized controlled trials, the EPPPIC (Evaluating Progestogens for Preventing Preterm birth International Collaborative) investigators compared vaginal progesterone, intramuscular 17-hydroxyprogesterone caproate  (17-OHPC), or oral progesterone with control or with each other in women at risk for PTB.³ Outcomes included PTB and the associated adverse neonatal and maternal outcomes.

The EPPPIC study’s main findings were:

• Singleton pregnancies at high risk for PTB due to prior sPTB or short cervix who received 17-OHPC or vaginal progesterone were less likely to deliver before  34 weeks’ gestation compared with those who received no treatment.
• There is a benefit to both 17-OHPC and vaginal progesterone in reducing the risk of PTB, with no clear evidence to support one intervention’s effectiveness over the other.
• There is benefit to either 17-OHPC or vaginal progesterone for CL less than 25 mm. The shorter the CL, the greater the absolute risk reduction on PTB.
• In multifetal pregnancies, use of 17-OHPC, when compared with placebo, was shown to increase the risk of preterm premature rupture of membranes. Neither 17-OHPC nor vaginal progesterone was found to reduce the risk of sPTB in multifetal pregnancies.³

What continues to change

While the March 30, 2021, statement from the Society for Maternal-Fetal Medicine (SMFM), “Response to EPPPIC and consideration for the use of progestogens for the prevention of preterm birth” (https://www .smfm.org/publications/383-smfm-stat ement-response-to-epppic-and-consider ations-of-the-use-of-progestogens-for-the -prevention-of-preterm-birth), stands, ACOG has withdrawn its accompanying Practice Advisory on guidance for integrating the EPPPIC findings.

In August 2022, the US Food and Drug Administration (FDA) granted a hearing on the Center for Drug Evaluation and Research’s proposal to withdraw approval for Makena (hydroxyprogesterone caproate injection, 250 mg/mL, once weekly) on the basis that available evidence does not demonstrate that it is effective for its approved indication to reduce the risk of PTB in women with a singleton pregnancy with a history of singleton sPTB.⁴

The key takeaway points from the FDA hearing (October 17–19, 2022) were:

• A better designed randomized controlled confirmatory trial is needed in the most at-risk patients to determine if Makena is effective for its approved indication.
• Makena and its approved generic equivalents remain on the market until the FDA makes its final decision regarding approval.⁴

Continue to: Managing pregnancies that result from IVF...

Society for Maternal-Fetal Medicine (SMFM); Ghidini A, Gandhi M, McCoy J, et al; Publications Committee. Society for Maternal-Fetal Medicine consult series #60: management of pregnancies resulting from in vitro fertilization. Am J Obstet Gynecol. 2022;226:B2-B12.

Assisted reproductive technology contributes to 1.6% of all infant births, and although most pregnancies are uncomplicated, some specific risks alter management.^5–7 For example, IVF is associated with increased rates of prematurity and its complications, fetal growth restriction, low birth weight, congenital anomalies, genetic abnormalities, and placental abnormalities. In addition, there is doubling of the risk of morbidities to the pregnant IVF patient, including but not limited to hypertensive disorders and diabetes. These complications are thought to be related to both the process of IVF itself as well as to conditions that contribute to subfertility and infertility in the first place.

Genetic screening and diagnostic testing options

IVF pregnancies have a documented increase in chromosomal abnormalities compared with spontaneously conceived pregnancies due to the following factors:

• karyotypic abnormalities in couples with infertility
• microdeletions on the Y chromosome in patients with oligospermia or azoospermia
• de novo chromosomal abnormalities in IVF pregnancies that utilize intracytoplasmic sperm injection (ICSI)
• fragile X mutations in patients with reduced ovarian reserve
• imprinting disorders in patients with fertility issues.

A common misconception is that preimplantation genetic testing renders prenatal genetic screening or testing unnecessary. However, preimplantation testing can be anywhere from 43% to 84% concordant with prenatal diagnostic testing due to biologic and technical factors. Therefore, all pregnancies should be offered the same options of aneuploidy screening as well as diagnostic testing. Pretest counseling should include an increased risk in IVF pregnancies of false-positives for the first-trimester screen and “no-call” results for cell-free fetal DNA. Additionally, diagnostic testing is recommended specifically in cases where mosaic embryos are transferred when euploid embryos are not available.

Counseling on fetal reduction for multifetal pregnancies

The risks of multifetal pregnancies (particularly higher order multiples) are significant and well documented for both the patient and the fetuses. It is therefore recommended that the option of multifetal pregnancy reduction be discussed, including the risks and benefits of reduction versus pregnancy continuation, timing, procedural considerations, and genetic testing options.^5,8

Detailed anatomic survey and fetal echocardiogram are indicated

Fetal anomalies, including congenital cardiac defects, occur at a higher rate in IVF pregnancies compared with spontaneously conceived pregnancies (475/10,000 live births vs 317/10,000 live births). Placental anomalies (such as placenta previa, vasa previa, and velamentous cord insertion) are also more common in this population. A detailed anatomic survey is therefore recommended for all IVF pregnancies and it is suggested that a fetal echocardiogram is offered these patients as well.

Pregnancy management and delivery considerations

Despite an increased risk of preterm birth, preeclampsia, and fetal growth restriction in IVF pregnancies (odds ratios range, 1.4–2), serial cervical lengths, serial growth ultrasound exams, and low-dose aspirin are not recommended for the sole indication of IVF. Due to lack of data on the utility of serial exams, a single screening cervical length at the time of anatomic survey and a third-trimester growth assessment are recommended. For aspirin, IVF qualifies as a “moderate” risk factor for preeclampsia; it is therefore recommended if another moderate risk factor is present (for example, nulliparity, obesity, or family history of preeclampsia).⁹

There is a 2- to 3-fold increased risk of stillbirth in IVF pregnancies; therefore, antenatal surveillance in the third trimester is recommended (weekly starting at 36 weeks for the sole indication of IVF).¹⁰ As no specific studies have evaluated the timing of delivery in IVF pregnancies, delivery recommendations include the option of 39-week delivery with shared decision-making with the patient.

Continue to: Evaluating and treating headaches in pregnancy and postpartum...

Evaluating and treating headaches in pregnancy and postpartum

American College of Obstetricians and Gynecologists. Clinical practice guideline no. 3: headaches in pregnancy and postpartum. Obstet Gynecol. 2022;139:944-972.

For obstetricians, headaches are a common and often frustrating condition to treat, as many of the available diagnostic tools and medications are either not recommended or have no data on use in pregnancy and lactation. Additionally, a headache is not always just a headache but could be a sign of a time-sensitive serious complication. An updated guideline from the American College of Obstetricians and Gynecologists approaches the topic of headaches in a stepwise algorithm that promotes efficiency and efficacy in diagnosis  and treatment.¹¹

Types of headaches

The primary headache types—migraine, cluster, and tension—are distinguished from each other by patient characteristics, quality, duration, location, and related symptoms. Reassuringly, headache frequency decreases by 30% to 80% during pregnancy, which allows for the option to decrease, change, or stop current medications, ideally prior to pregnancy. Prevention via use of calcium channel blockers, antihistamines, or β-blockers is recommended, as requiring acute treatments more than 2 days per week increases the risk of medication overuse headaches.

Treating acute headache

For patients who present with an acute headache consistent with their usual type, treatment starts with known medications that are compatible with pregnancy and proceeds in a stepwise fashion:

1. Acetaminophen 1,000 mg orally with or without caffeine 130 mg orally (maximum dose, acetaminophen < 3.25–4 g per day, caffeine 200 mg per day)

2. Metoclopramide 10 mg intravenously with or without diphenhydramine 25 mg intravenously (for nausea and to counteract restlessness and offer sedation)

3. If headache continues after steps 1 and 2, consider the following secondary treatment options: magnesium sulfate 1–2 g intravenously, sumatriptan 6 mg subcutaneously or 20-mg nasal spray, ibuprofen 600 mg orally once, or ketorolac 30 mg intravenously once (second trimester only)

4. If continued treatment and/or hospitalization is required after step 3, steroids can be used: prednisone 20 mg 4 times a day for 2 days or methylprednisolone 4-mg dose pack over 6 days

5. Do not use butalbital, opioids, or ergotamines due to lack of efficacy in providing additional pain relief, potential for addiction, risk of medication overuse headaches, and association with fetal/ pregnancy abnormalities.

Consider secondary headache

An acute headache discordant from the patient’s usual type or with concerning symptoms (“red flags”) requires consideration of secondary headaches as well as a comprehensive symptom evaluation, imaging, and consultation as needed. While secondary headaches postpartum are most likely musculoskeletal in nature, the following symptoms need to be evaluated immediately:

• rapid onset/change from baseline
• “thunderclap” nature
• hypertension
• fever
• focal neurologic deficits (blurry vision or blindness, confusion, seizures)
• altered consciousness
• laboratory abnormalities.

The differential diagnosis includes preeclampsia, reversible cerebral vasoconstriction syndrome (RCVS), posterior reversible encephalopathy syndrome (PRES), infection, cerebral venous sinus thrombosis (CVST), post–dural puncture (PDP) headache, idiopathic intracranial hypertension (IIH), and less likely, carotid dissection, subarachnoid hemorrhage, intracranial hemorrhage, pituitary apoplexy, or neoplasm.

Treatment. Individualized treatment depends on the diagnosis. Preeclampsia with severe features is treated with antihypertensive medication, magnesium sulfate, and delivery planning. PDP headache is treated with epidural blood patch, sphenopalatine block, or occipital block with an anesthesiology consultation. If preeclampsia and PDP are ruled out, or if there are more concerning neurologic features, imaging is essential, as 25% of pregnant patients with acute headaches will have a secondary etiology. Magnetic resonance imaging without contrast is preferred due to concerns about gadolinium crossing the placenta and the lack of data on long-term accumulation in fetal  tissues. Once diagnosed on imaging, PRES and RCVS are treated with antihypertensives and delivery. CVST is treated with anticoagulation and a thrombophilia workup. IIH may be treated with acetazolamide after 20 weeks or serial lumbar punctures. Intracranial vascular abnormalities may be treated with endoscopic resection and steroids. ●

In the musical Hamilton, there is a line from the song “The Election of 1800” in which, after a tumultuous time, Thomas Jefferson pleads for a sense of normalcy with, “Can we get back to politics?”

Trying to get back to “normal,” whatever that is, characterized the year 2022. Peeking out from under the constant shadow of the COVID-19 pandemic (not really gone, definitely not forgotten) were some blockbuster obstetrical headlines, including those on the CHAP (Chronic Hypertension and Pregnancy) trial and the impact of the Dobbs v Jackson Supreme Court decision. As these have been extensively covered in both OBG Management and other publications, in this Update we simply ask, “Can we get back to obstetrics?” as we focus on some straightforward patient care guidelines.

Thus, we offer updated information on the use of progesterone for preterm birth prevention, management of pregnancies that result from in vitro fertilization (IVF), and headache management in pregnant and postpartum patients.

Society guidance and FDA  advisement on the use of  progesterone for the prevention  of spontaneous preterm birth

American College of Obstetricians and Gynecologists’ Committee on Practice Bulletins–Obstetrics. Prediction and prevention of spontaneous preterm birth. ACOG practice bulletin no. 234. Obstet Gynecol. 2021;138:e65-e90.

EPPPIC Group. Evaluating Progestogens for Preventing Preterm birth International Collaborative (EPPPIC): meta-analysis of individual participant data from randomised controlled trials. Lancet. 2021;397:1183-1194.

This is not déjà vu! Progesterone and spontaneous preterm birth (sPTB) is a hot topic again. If you wonder what to tell your patients, you are not alone. Preterm birth (PTB) continues to pose a challenge in obstetrics, with a most recently reported overall rate of 10.49%¹ in the United States—a 4% increase from 2019. Preterm birth accounts for approximately 75% of perinatal mortality and more than half of neonatal morbidity.²

What has not changed

A recent practice bulletin from the American College of Obstetricians and Gynecologists (ACOG) notes that some risk factors and screening assessments for PTB remain unchanged, including²:

• A history of PTB increases the risk for subsequent PTB. Risk increases with the number of prior preterm deliveries.
• A short cervix (<25 mm between 16 and  24 weeks’ gestation) is a risk factor for sPTB.
• The cervix should be visualized during the anatomy ultrasound exam (18 0/7 to 22 6/7 weeks’ gestation) in all pregnant patients regardless of prior birth history. If the cervix length (CL) appears shortened on transabdominal imaging, transvaginal (TV) imaging should be performed.
• Patients with a current singleton pregnancy and history of sPTB should have serial TV cervical measurements between 16 0/7 and 24 0/7 weeks’ gestation.²

EPPPIC changes and key takeaway points

In a meta-analysis of data from 31 randomized controlled trials, the EPPPIC (Evaluating Progestogens for Preventing Preterm birth International Collaborative) investigators compared vaginal progesterone, intramuscular 17-hydroxyprogesterone caproate  (17-OHPC), or oral progesterone with control or with each other in women at risk for PTB.³ Outcomes included PTB and the associated adverse neonatal and maternal outcomes.

The EPPPIC study’s main findings were:

• Singleton pregnancies at high risk for PTB due to prior sPTB or short cervix who received 17-OHPC or vaginal progesterone were less likely to deliver before  34 weeks’ gestation compared with those who received no treatment.
• There is a benefit to both 17-OHPC and vaginal progesterone in reducing the risk of PTB, with no clear evidence to support one intervention’s effectiveness over the other.
• There is benefit to either 17-OHPC or vaginal progesterone for CL less than 25 mm. The shorter the CL, the greater the absolute risk reduction on PTB.
• In multifetal pregnancies, use of 17-OHPC, when compared with placebo, was shown to increase the risk of preterm premature rupture of membranes. Neither 17-OHPC nor vaginal progesterone was found to reduce the risk of sPTB in multifetal pregnancies.³

What continues to change

While the March 30, 2021, statement from the Society for Maternal-Fetal Medicine (SMFM), “Response to EPPPIC and consideration for the use of progestogens for the prevention of preterm birth” (https://www .smfm.org/publications/383-smfm-stat ement-response-to-epppic-and-consider ations-of-the-use-of-progestogens-for-the -prevention-of-preterm-birth), stands, ACOG has withdrawn its accompanying Practice Advisory on guidance for integrating the EPPPIC findings.

In August 2022, the US Food and Drug Administration (FDA) granted a hearing on the Center for Drug Evaluation and Research’s proposal to withdraw approval for Makena (hydroxyprogesterone caproate injection, 250 mg/mL, once weekly) on the basis that available evidence does not demonstrate that it is effective for its approved indication to reduce the risk of PTB in women with a singleton pregnancy with a history of singleton sPTB.⁴

The key takeaway points from the FDA hearing (October 17–19, 2022) were:

• A better designed randomized controlled confirmatory trial is needed in the most at-risk patients to determine if Makena is effective for its approved indication.
• Makena and its approved generic equivalents remain on the market until the FDA makes its final decision regarding approval.⁴

Continue to: Managing pregnancies that result from IVF...

Society for Maternal-Fetal Medicine (SMFM); Ghidini A, Gandhi M, McCoy J, et al; Publications Committee. Society for Maternal-Fetal Medicine consult series #60: management of pregnancies resulting from in vitro fertilization. Am J Obstet Gynecol. 2022;226:B2-B12.

Assisted reproductive technology contributes to 1.6% of all infant births, and although most pregnancies are uncomplicated, some specific risks alter management.^5–7 For example, IVF is associated with increased rates of prematurity and its complications, fetal growth restriction, low birth weight, congenital anomalies, genetic abnormalities, and placental abnormalities. In addition, there is doubling of the risk of morbidities to the pregnant IVF patient, including but not limited to hypertensive disorders and diabetes. These complications are thought to be related to both the process of IVF itself as well as to conditions that contribute to subfertility and infertility in the first place.

Genetic screening and diagnostic testing options

IVF pregnancies have a documented increase in chromosomal abnormalities compared with spontaneously conceived pregnancies due to the following factors:

• karyotypic abnormalities in couples with infertility
• microdeletions on the Y chromosome in patients with oligospermia or azoospermia
• de novo chromosomal abnormalities in IVF pregnancies that utilize intracytoplasmic sperm injection (ICSI)
• fragile X mutations in patients with reduced ovarian reserve
• imprinting disorders in patients with fertility issues.

A common misconception is that preimplantation genetic testing renders prenatal genetic screening or testing unnecessary. However, preimplantation testing can be anywhere from 43% to 84% concordant with prenatal diagnostic testing due to biologic and technical factors. Therefore, all pregnancies should be offered the same options of aneuploidy screening as well as diagnostic testing. Pretest counseling should include an increased risk in IVF pregnancies of false-positives for the first-trimester screen and “no-call” results for cell-free fetal DNA. Additionally, diagnostic testing is recommended specifically in cases where mosaic embryos are transferred when euploid embryos are not available.

Counseling on fetal reduction for multifetal pregnancies

The risks of multifetal pregnancies (particularly higher order multiples) are significant and well documented for both the patient and the fetuses. It is therefore recommended that the option of multifetal pregnancy reduction be discussed, including the risks and benefits of reduction versus pregnancy continuation, timing, procedural considerations, and genetic testing options.^5,8

Detailed anatomic survey and fetal echocardiogram are indicated

Fetal anomalies, including congenital cardiac defects, occur at a higher rate in IVF pregnancies compared with spontaneously conceived pregnancies (475/10,000 live births vs 317/10,000 live births). Placental anomalies (such as placenta previa, vasa previa, and velamentous cord insertion) are also more common in this population. A detailed anatomic survey is therefore recommended for all IVF pregnancies and it is suggested that a fetal echocardiogram is offered these patients as well.

Pregnancy management and delivery considerations

Despite an increased risk of preterm birth, preeclampsia, and fetal growth restriction in IVF pregnancies (odds ratios range, 1.4–2), serial cervical lengths, serial growth ultrasound exams, and low-dose aspirin are not recommended for the sole indication of IVF. Due to lack of data on the utility of serial exams, a single screening cervical length at the time of anatomic survey and a third-trimester growth assessment are recommended. For aspirin, IVF qualifies as a “moderate” risk factor for preeclampsia; it is therefore recommended if another moderate risk factor is present (for example, nulliparity, obesity, or family history of preeclampsia).⁹

There is a 2- to 3-fold increased risk of stillbirth in IVF pregnancies; therefore, antenatal surveillance in the third trimester is recommended (weekly starting at 36 weeks for the sole indication of IVF).¹⁰ As no specific studies have evaluated the timing of delivery in IVF pregnancies, delivery recommendations include the option of 39-week delivery with shared decision-making with the patient.

Continue to: Evaluating and treating headaches in pregnancy and postpartum...

Evaluating and treating headaches in pregnancy and postpartum

American College of Obstetricians and Gynecologists. Clinical practice guideline no. 3: headaches in pregnancy and postpartum. Obstet Gynecol. 2022;139:944-972.

For obstetricians, headaches are a common and often frustrating condition to treat, as many of the available diagnostic tools and medications are either not recommended or have no data on use in pregnancy and lactation. Additionally, a headache is not always just a headache but could be a sign of a time-sensitive serious complication. An updated guideline from the American College of Obstetricians and Gynecologists approaches the topic of headaches in a stepwise algorithm that promotes efficiency and efficacy in diagnosis  and treatment.¹¹

Types of headaches

The primary headache types—migraine, cluster, and tension—are distinguished from each other by patient characteristics, quality, duration, location, and related symptoms. Reassuringly, headache frequency decreases by 30% to 80% during pregnancy, which allows for the option to decrease, change, or stop current medications, ideally prior to pregnancy. Prevention via use of calcium channel blockers, antihistamines, or β-blockers is recommended, as requiring acute treatments more than 2 days per week increases the risk of medication overuse headaches.

Treating acute headache

For patients who present with an acute headache consistent with their usual type, treatment starts with known medications that are compatible with pregnancy and proceeds in a stepwise fashion:

1. Acetaminophen 1,000 mg orally with or without caffeine 130 mg orally (maximum dose, acetaminophen < 3.25–4 g per day, caffeine 200 mg per day)

2. Metoclopramide 10 mg intravenously with or without diphenhydramine 25 mg intravenously (for nausea and to counteract restlessness and offer sedation)

3. If headache continues after steps 1 and 2, consider the following secondary treatment options: magnesium sulfate 1–2 g intravenously, sumatriptan 6 mg subcutaneously or 20-mg nasal spray, ibuprofen 600 mg orally once, or ketorolac 30 mg intravenously once (second trimester only)

4. If continued treatment and/or hospitalization is required after step 3, steroids can be used: prednisone 20 mg 4 times a day for 2 days or methylprednisolone 4-mg dose pack over 6 days

5. Do not use butalbital, opioids, or ergotamines due to lack of efficacy in providing additional pain relief, potential for addiction, risk of medication overuse headaches, and association with fetal/ pregnancy abnormalities.

Consider secondary headache

An acute headache discordant from the patient’s usual type or with concerning symptoms (“red flags”) requires consideration of secondary headaches as well as a comprehensive symptom evaluation, imaging, and consultation as needed. While secondary headaches postpartum are most likely musculoskeletal in nature, the following symptoms need to be evaluated immediately:

• rapid onset/change from baseline
• “thunderclap” nature
• hypertension
• fever
• focal neurologic deficits (blurry vision or blindness, confusion, seizures)
• altered consciousness
• laboratory abnormalities.

The differential diagnosis includes preeclampsia, reversible cerebral vasoconstriction syndrome (RCVS), posterior reversible encephalopathy syndrome (PRES), infection, cerebral venous sinus thrombosis (CVST), post–dural puncture (PDP) headache, idiopathic intracranial hypertension (IIH), and less likely, carotid dissection, subarachnoid hemorrhage, intracranial hemorrhage, pituitary apoplexy, or neoplasm.

Treatment. Individualized treatment depends on the diagnosis. Preeclampsia with severe features is treated with antihypertensive medication, magnesium sulfate, and delivery planning. PDP headache is treated with epidural blood patch, sphenopalatine block, or occipital block with an anesthesiology consultation. If preeclampsia and PDP are ruled out, or if there are more concerning neurologic features, imaging is essential, as 25% of pregnant patients with acute headaches will have a secondary etiology. Magnetic resonance imaging without contrast is preferred due to concerns about gadolinium crossing the placenta and the lack of data on long-term accumulation in fetal  tissues. Once diagnosed on imaging, PRES and RCVS are treated with antihypertensives and delivery. CVST is treated with anticoagulation and a thrombophilia workup. IIH may be treated with acetazolamide after 20 weeks or serial lumbar punctures. Intracranial vascular abnormalities may be treated with endoscopic resection and steroids. ●

Postpartum/perinatal depression (PPD) remains the most common complication in modern obstetrics, with a prevalence of 10%-15% based on multiple studies over the last 2 decades. Over those same 2 decades, there has been growing interest and motivation across the country – from small community hospitals to major academic centers – to promote screening. Such screening is integrated into obstetrical practices, typically using the Edinburgh Postnatal Depression Scale (EPDS), the most widely used validated screen for PPD globally.

As mentioned in previous columns, the U.S. Preventive Services Task Force recommended screening for PPD in 2016, which includes screening women at highest risk, and both acutely treating and preventing PPD.

Since then, screening women for a common clinical problem like PPD has been widely adopted by clinicians representing a broad spectrum of interdisciplinary care. Providers who are engaged in the treatment of postpartum women – obstetricians, psychiatrists, doulas, lactation consultants, facilitators of postpartum support groups, and advocacy groups among others – are included.

An open question and one of great concern recently to our group and others has been what happens after screening. It is clear that identification of PPD per se is not necessarily a challenge, and we have multiple effective treatments from antidepressants to mindfulness-based cognitive therapy to cognitive-behavioral interventions. There is also a growing number of digital applications aimed at mitigation of depressive symptoms in women with postpartum major depressive disorder. One unanswered question is how to engage women after identification of PPD and how to facilitate access to care in a way that maximizes the likelihood that women who actually are suffering from PPD get adequate treatment.

The “perinatal treatment cascade” refers to the majority of women who, on the other side of identification of PPD, fail to receive adequate treatment and continue to have persistent depression. This is perhaps the greatest challenge to the field and to clinicians – how do we, on the other side of screening, see that these women get access to care and get well?

With that backdrop, it is surprising that the Canadian Task Force on Preventive Health Care has recently recommended against screening with systematic questionnaires, noting that benefits were unclear and not a particular advantage relative to standard practice. The recommendation carries an assumption that standard practice involves queries about mental health. While the task force continues to recommend screening for PPD, their recommendation against screening with a standardized questionnaire represents a bold, sweeping, if not myopic view.

While the Canadian Task Force on Preventive Health Care made their recommendation based on a single randomized controlled trial with the assumption that women were getting mental health counseling, and that women liked getting mental health engagement around their depression, that is not a uniform part of practice. Thus, it is puzzling why the task force would make the recommendation based on such sparse data.

The way to optimize access to care and referral systems for women who are suffering from PPD is not to remove a part of the system that’s already working. Well-validated questionnaires such as the EPDS are easy to administer and are routinely integrated into the electronic health systems records of both small and large centers. These questionnaires are an inexpensive way to increase the likelihood that women get identified and referred for a spectrum of potentially helpful interventions.

PPD is also easy to treat with medications and a wide spectrum of nonpharmacologic interventions. Novel interventions are also being explored to maximize access for women with postpartum mood and anxiety disorders such as peer-delivered behavioral activation and cognitive-behavioral therapy, which could be community based and implemented from urban to rural settings across the United States.

What may need the greatest study is the path to accessing effective treatments and resources for these women and this problem has prompted our group to explore these issues in our more recent investigations. Better understanding of those factors that limit access to mental health providers with expertise in perinatal mental health to the logistical issues of navigating the health care system for sleep-deprived new moms and their families demands greater attention and clearer answers.

The whole field has an obligation to postpartum women to figure out the amalgam of practitioners, resources, and platforms that need to be used to engage women so that they get effective treatment – because we have effective treatments. But the solution to improving perinatal mental health outcomes, unlike the approach of our colleagues in Canada, is not to be found in abandoning questionnaire-based screening, but in identifying the best ways to prevent PPD and to maximize access to care.

Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital (MGH) in Boston, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications. Email Dr. Cohen at [email protected].

Postpartum/perinatal depression (PPD) remains the most common complication in modern obstetrics, with a prevalence of 10%-15% based on multiple studies over the last 2 decades. Over those same 2 decades, there has been growing interest and motivation across the country – from small community hospitals to major academic centers – to promote screening. Such screening is integrated into obstetrical practices, typically using the Edinburgh Postnatal Depression Scale (EPDS), the most widely used validated screen for PPD globally.

As mentioned in previous columns, the U.S. Preventive Services Task Force recommended screening for PPD in 2016, which includes screening women at highest risk, and both acutely treating and preventing PPD.

Since then, screening women for a common clinical problem like PPD has been widely adopted by clinicians representing a broad spectrum of interdisciplinary care. Providers who are engaged in the treatment of postpartum women – obstetricians, psychiatrists, doulas, lactation consultants, facilitators of postpartum support groups, and advocacy groups among others – are included.

An open question and one of great concern recently to our group and others has been what happens after screening. It is clear that identification of PPD per se is not necessarily a challenge, and we have multiple effective treatments from antidepressants to mindfulness-based cognitive therapy to cognitive-behavioral interventions. There is also a growing number of digital applications aimed at mitigation of depressive symptoms in women with postpartum major depressive disorder. One unanswered question is how to engage women after identification of PPD and how to facilitate access to care in a way that maximizes the likelihood that women who actually are suffering from PPD get adequate treatment.

The “perinatal treatment cascade” refers to the majority of women who, on the other side of identification of PPD, fail to receive adequate treatment and continue to have persistent depression. This is perhaps the greatest challenge to the field and to clinicians – how do we, on the other side of screening, see that these women get access to care and get well?

With that backdrop, it is surprising that the Canadian Task Force on Preventive Health Care has recently recommended against screening with systematic questionnaires, noting that benefits were unclear and not a particular advantage relative to standard practice. The recommendation carries an assumption that standard practice involves queries about mental health. While the task force continues to recommend screening for PPD, their recommendation against screening with a standardized questionnaire represents a bold, sweeping, if not myopic view.

While the Canadian Task Force on Preventive Health Care made their recommendation based on a single randomized controlled trial with the assumption that women were getting mental health counseling, and that women liked getting mental health engagement around their depression, that is not a uniform part of practice. Thus, it is puzzling why the task force would make the recommendation based on such sparse data.

The way to optimize access to care and referral systems for women who are suffering from PPD is not to remove a part of the system that’s already working. Well-validated questionnaires such as the EPDS are easy to administer and are routinely integrated into the electronic health systems records of both small and large centers. These questionnaires are an inexpensive way to increase the likelihood that women get identified and referred for a spectrum of potentially helpful interventions.

PPD is also easy to treat with medications and a wide spectrum of nonpharmacologic interventions. Novel interventions are also being explored to maximize access for women with postpartum mood and anxiety disorders such as peer-delivered behavioral activation and cognitive-behavioral therapy, which could be community based and implemented from urban to rural settings across the United States.

What may need the greatest study is the path to accessing effective treatments and resources for these women and this problem has prompted our group to explore these issues in our more recent investigations. Better understanding of those factors that limit access to mental health providers with expertise in perinatal mental health to the logistical issues of navigating the health care system for sleep-deprived new moms and their families demands greater attention and clearer answers.

The whole field has an obligation to postpartum women to figure out the amalgam of practitioners, resources, and platforms that need to be used to engage women so that they get effective treatment – because we have effective treatments. But the solution to improving perinatal mental health outcomes, unlike the approach of our colleagues in Canada, is not to be found in abandoning questionnaire-based screening, but in identifying the best ways to prevent PPD and to maximize access to care.

Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital (MGH) in Boston, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications. Email Dr. Cohen at [email protected].

Postpartum/perinatal depression (PPD) remains the most common complication in modern obstetrics, with a prevalence of 10%-15% based on multiple studies over the last 2 decades. Over those same 2 decades, there has been growing interest and motivation across the country – from small community hospitals to major academic centers – to promote screening. Such screening is integrated into obstetrical practices, typically using the Edinburgh Postnatal Depression Scale (EPDS), the most widely used validated screen for PPD globally.

As mentioned in previous columns, the U.S. Preventive Services Task Force recommended screening for PPD in 2016, which includes screening women at highest risk, and both acutely treating and preventing PPD.

Since then, screening women for a common clinical problem like PPD has been widely adopted by clinicians representing a broad spectrum of interdisciplinary care. Providers who are engaged in the treatment of postpartum women – obstetricians, psychiatrists, doulas, lactation consultants, facilitators of postpartum support groups, and advocacy groups among others – are included.

An open question and one of great concern recently to our group and others has been what happens after screening. It is clear that identification of PPD per se is not necessarily a challenge, and we have multiple effective treatments from antidepressants to mindfulness-based cognitive therapy to cognitive-behavioral interventions. There is also a growing number of digital applications aimed at mitigation of depressive symptoms in women with postpartum major depressive disorder. One unanswered question is how to engage women after identification of PPD and how to facilitate access to care in a way that maximizes the likelihood that women who actually are suffering from PPD get adequate treatment.

The “perinatal treatment cascade” refers to the majority of women who, on the other side of identification of PPD, fail to receive adequate treatment and continue to have persistent depression. This is perhaps the greatest challenge to the field and to clinicians – how do we, on the other side of screening, see that these women get access to care and get well?

With that backdrop, it is surprising that the Canadian Task Force on Preventive Health Care has recently recommended against screening with systematic questionnaires, noting that benefits were unclear and not a particular advantage relative to standard practice. The recommendation carries an assumption that standard practice involves queries about mental health. While the task force continues to recommend screening for PPD, their recommendation against screening with a standardized questionnaire represents a bold, sweeping, if not myopic view.

While the Canadian Task Force on Preventive Health Care made their recommendation based on a single randomized controlled trial with the assumption that women were getting mental health counseling, and that women liked getting mental health engagement around their depression, that is not a uniform part of practice. Thus, it is puzzling why the task force would make the recommendation based on such sparse data.

The way to optimize access to care and referral systems for women who are suffering from PPD is not to remove a part of the system that’s already working. Well-validated questionnaires such as the EPDS are easy to administer and are routinely integrated into the electronic health systems records of both small and large centers. These questionnaires are an inexpensive way to increase the likelihood that women get identified and referred for a spectrum of potentially helpful interventions.

PPD is also easy to treat with medications and a wide spectrum of nonpharmacologic interventions. Novel interventions are also being explored to maximize access for women with postpartum mood and anxiety disorders such as peer-delivered behavioral activation and cognitive-behavioral therapy, which could be community based and implemented from urban to rural settings across the United States.

What may need the greatest study is the path to accessing effective treatments and resources for these women and this problem has prompted our group to explore these issues in our more recent investigations. Better understanding of those factors that limit access to mental health providers with expertise in perinatal mental health to the logistical issues of navigating the health care system for sleep-deprived new moms and their families demands greater attention and clearer answers.

The whole field has an obligation to postpartum women to figure out the amalgam of practitioners, resources, and platforms that need to be used to engage women so that they get effective treatment – because we have effective treatments. But the solution to improving perinatal mental health outcomes, unlike the approach of our colleagues in Canada, is not to be found in abandoning questionnaire-based screening, but in identifying the best ways to prevent PPD and to maximize access to care.

Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital (MGH) in Boston, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications. Email Dr. Cohen at [email protected].

Women infected with COVID-19 during pregnancy are seven times more likely to die during childbirth or during the pregnancy than uninfected pregnant women, a new study shows. The new report also warns of many other severe complications linked with the virus during pregnancy, as well as risks to the baby after birth.

But the researchers said they did not find that COVID-19 infection during pregnancy impacted the risk of stillbirth or a baby’s growth rate during pregnancy.

The study, which was a meta-analysis of previous research, was published Jan. 16 in the journal BMJ Global Health. Data from 12 studies from 12 countries were combined so researchers could analyze outcomes for 13,136 pregnant women.

Babies born to mothers who were infected with COVID during pregnancy had almost double the risk of needing stays in the neonatal intensive care unit and also were more likely to be born preterm, compared with babies who were born to pregnant women who didn’t get COVID.

The researchers also found that pregnant women who got COVID were more likely to be admitted to intensive care units, need a ventilator to help them survive, develop dangerous blood clots, or develop preeclampsia, which is a high blood pressure disorder that can be fatal for the mother or baby.

One of the strengths of the study was that it included women in different trimesters during pregnancy.

“That’s something new here too is that COVID at any time during pregnancy did bring this extra risk onto mom and babies,” said lead author Emily R. Smith, ScD, MPH, assistant professor of global health at the George Washington University, in a video statement. 

The report is prompting calls for improved efforts to convince pregnant women to get vaccinated for COVID-19. The rate among them remains low: About 1 in 5 pregnant women had received the most updated COVID-19 booster as of Jan. 7, according to the CDC.

“The implications here are that it’s really important that if you’re pregnant or if you’re thinking about becoming pregnant, to get vaccinated,” Dr. Smith said. “This can really reduce the risk of having some of these bad outcomes for mom or for baby.”

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

Women infected with COVID-19 during pregnancy are seven times more likely to die during childbirth or during the pregnancy than uninfected pregnant women, a new study shows. The new report also warns of many other severe complications linked with the virus during pregnancy, as well as risks to the baby after birth.

But the researchers said they did not find that COVID-19 infection during pregnancy impacted the risk of stillbirth or a baby’s growth rate during pregnancy.

The study, which was a meta-analysis of previous research, was published Jan. 16 in the journal BMJ Global Health. Data from 12 studies from 12 countries were combined so researchers could analyze outcomes for 13,136 pregnant women.

Babies born to mothers who were infected with COVID during pregnancy had almost double the risk of needing stays in the neonatal intensive care unit and also were more likely to be born preterm, compared with babies who were born to pregnant women who didn’t get COVID.

The researchers also found that pregnant women who got COVID were more likely to be admitted to intensive care units, need a ventilator to help them survive, develop dangerous blood clots, or develop preeclampsia, which is a high blood pressure disorder that can be fatal for the mother or baby.

One of the strengths of the study was that it included women in different trimesters during pregnancy.

“That’s something new here too is that COVID at any time during pregnancy did bring this extra risk onto mom and babies,” said lead author Emily R. Smith, ScD, MPH, assistant professor of global health at the George Washington University, in a video statement. 

The report is prompting calls for improved efforts to convince pregnant women to get vaccinated for COVID-19. The rate among them remains low: About 1 in 5 pregnant women had received the most updated COVID-19 booster as of Jan. 7, according to the CDC.

“The implications here are that it’s really important that if you’re pregnant or if you’re thinking about becoming pregnant, to get vaccinated,” Dr. Smith said. “This can really reduce the risk of having some of these bad outcomes for mom or for baby.”

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

Women infected with COVID-19 during pregnancy are seven times more likely to die during childbirth or during the pregnancy than uninfected pregnant women, a new study shows. The new report also warns of many other severe complications linked with the virus during pregnancy, as well as risks to the baby after birth.

But the researchers said they did not find that COVID-19 infection during pregnancy impacted the risk of stillbirth or a baby’s growth rate during pregnancy.

The study, which was a meta-analysis of previous research, was published Jan. 16 in the journal BMJ Global Health. Data from 12 studies from 12 countries were combined so researchers could analyze outcomes for 13,136 pregnant women.

Babies born to mothers who were infected with COVID during pregnancy had almost double the risk of needing stays in the neonatal intensive care unit and also were more likely to be born preterm, compared with babies who were born to pregnant women who didn’t get COVID.

The researchers also found that pregnant women who got COVID were more likely to be admitted to intensive care units, need a ventilator to help them survive, develop dangerous blood clots, or develop preeclampsia, which is a high blood pressure disorder that can be fatal for the mother or baby.

One of the strengths of the study was that it included women in different trimesters during pregnancy.

“That’s something new here too is that COVID at any time during pregnancy did bring this extra risk onto mom and babies,” said lead author Emily R. Smith, ScD, MPH, assistant professor of global health at the George Washington University, in a video statement. 

The report is prompting calls for improved efforts to convince pregnant women to get vaccinated for COVID-19. The rate among them remains low: About 1 in 5 pregnant women had received the most updated COVID-19 booster as of Jan. 7, according to the CDC.

“The implications here are that it’s really important that if you’re pregnant or if you’re thinking about becoming pregnant, to get vaccinated,” Dr. Smith said. “This can really reduce the risk of having some of these bad outcomes for mom or for baby.”

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

Women living in states that expanded Medicaid over the past decade were nearly 20% less likely to be hospitalized within 2 months of giving birth, according to a first-of-its-kind study published in Health Affairs.

Researchers analyzed patient records from eight states – four that expanded Medicaid insurance to include a broader swath of residents following the implementation of the Affordable Care Act, and four states that did not.

Hospitalizations in the 60 days after a woman gave birth fell by 17% in states that expanded Medicaid. The analysis also revealed an 8% drop in hospitalizations between 61 days and 6 months post partum.

“This is a very meaningful decline in hospitalization rates,” said Laura Wherry, PhD, a professor of economics and public service at New York University and a co-author of the study.

Women in states that chose not to expand Medicaid experienced a 7% increase in postpartum hospitalizations during that same time frame, the researchers report.

Many states raised income eligibility thresholds to 138% of the federal poverty level in 2014 with the implementation of the Affordable Care Act, which resulted in more coverage for low-income expectant mothers. To date, a dozen states have not implemented Medicaid expansion.

Dr. Wherry and her colleague wanted to take a closer look at outcomes for pregnant women during the postpartum period, both before and after states chose to expand Medicaid.

“A lot of prior work looking at the Medicaid program examined huge expansions to cover pregnant women during pregnancy, but often other periods of a woman’s life have been overlooked,” Dr. Wherry said. “What we were interested in is how that changed with the Affordable Care Act. You no longer needed to be pregnant to qualify.”

The researchers analyzed hospital discharge data between 2010 and 2017 before and after expansion in Iowa, Maryland, New Mexico, and Washington, which expanded coverage under Medicaid, and Florida, Georgia, Mississippi, and Utah, which did not do so.

Prior to 2014, fewer than 2% of births resulted in a postpartum hospitalization during the 60-day period in Medicaid expansion states. But in states that expanded Medicaid, hospitalizations decreased by 0.289 percentage points (P = .052), or 17% during the 60-day post-birth period.

Approximately 75% of the decline was attributed to diagnoses related to complications in pregnancy, childbirth, and the postpartum period.

Dr. Wherry said a variety of factors possibly drove down hospitalizations for new mothers who were able to obtain Medicaid coverage, including access to robust prenatal care, preconception counseling, and improved management of postpartum conditions outside the hospital.

The study provides a strategy for tackling the rising rate of maternal mortality in the United States, an increase largely attributed to postpartum deaths, said Lindsay Admon, MD, an ob.gyn. at the University of Michigan Medical School in Ann Arbor.

“This is one of the first studies showing or suggesting that Medicaid expansion not only led to improvements in Medicaid insurance but health outcomes as well,” said Dr. Admon, who is also researching maternal health and expanded Medicaid coverage.

Federal law has long required states to provide coverage for pregnant women up to 60 days post partum.

The 2021 American Rescue Act allowed states to extend coverage for pregnant women beyond the federal requirement to a year. More than half of states have chosen to do so. Since the study indicates that Medicaid expansion improves outcomes for these enrollees, Dr. Wherry and Dr. Admon said they hope state officials will consider the new findings during discussions to utilize the Rescue Act Coverage for pregnant women.

Dr. Wherry received support for the study from the Robert Wood Johnson Foundation Policies for Action Program and grant funding from the National Institute on Aging and the National Institute of Child Health and Human Development. Another author received grants from the Agency for Healthcare Research and Quality and the National Institute of Child Health and Human Development.

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

Women living in states that expanded Medicaid over the past decade were nearly 20% less likely to be hospitalized within 2 months of giving birth, according to a first-of-its-kind study published in Health Affairs.

Researchers analyzed patient records from eight states – four that expanded Medicaid insurance to include a broader swath of residents following the implementation of the Affordable Care Act, and four states that did not.

Hospitalizations in the 60 days after a woman gave birth fell by 17% in states that expanded Medicaid. The analysis also revealed an 8% drop in hospitalizations between 61 days and 6 months post partum.

“This is a very meaningful decline in hospitalization rates,” said Laura Wherry, PhD, a professor of economics and public service at New York University and a co-author of the study.

Women in states that chose not to expand Medicaid experienced a 7% increase in postpartum hospitalizations during that same time frame, the researchers report.

Many states raised income eligibility thresholds to 138% of the federal poverty level in 2014 with the implementation of the Affordable Care Act, which resulted in more coverage for low-income expectant mothers. To date, a dozen states have not implemented Medicaid expansion.

Dr. Wherry and her colleague wanted to take a closer look at outcomes for pregnant women during the postpartum period, both before and after states chose to expand Medicaid.

“A lot of prior work looking at the Medicaid program examined huge expansions to cover pregnant women during pregnancy, but often other periods of a woman’s life have been overlooked,” Dr. Wherry said. “What we were interested in is how that changed with the Affordable Care Act. You no longer needed to be pregnant to qualify.”

The researchers analyzed hospital discharge data between 2010 and 2017 before and after expansion in Iowa, Maryland, New Mexico, and Washington, which expanded coverage under Medicaid, and Florida, Georgia, Mississippi, and Utah, which did not do so.

Prior to 2014, fewer than 2% of births resulted in a postpartum hospitalization during the 60-day period in Medicaid expansion states. But in states that expanded Medicaid, hospitalizations decreased by 0.289 percentage points (P = .052), or 17% during the 60-day post-birth period.

Approximately 75% of the decline was attributed to diagnoses related to complications in pregnancy, childbirth, and the postpartum period.

Dr. Wherry said a variety of factors possibly drove down hospitalizations for new mothers who were able to obtain Medicaid coverage, including access to robust prenatal care, preconception counseling, and improved management of postpartum conditions outside the hospital.

The study provides a strategy for tackling the rising rate of maternal mortality in the United States, an increase largely attributed to postpartum deaths, said Lindsay Admon, MD, an ob.gyn. at the University of Michigan Medical School in Ann Arbor.

“This is one of the first studies showing or suggesting that Medicaid expansion not only led to improvements in Medicaid insurance but health outcomes as well,” said Dr. Admon, who is also researching maternal health and expanded Medicaid coverage.

Federal law has long required states to provide coverage for pregnant women up to 60 days post partum.

The 2021 American Rescue Act allowed states to extend coverage for pregnant women beyond the federal requirement to a year. More than half of states have chosen to do so. Since the study indicates that Medicaid expansion improves outcomes for these enrollees, Dr. Wherry and Dr. Admon said they hope state officials will consider the new findings during discussions to utilize the Rescue Act Coverage for pregnant women.

Dr. Wherry received support for the study from the Robert Wood Johnson Foundation Policies for Action Program and grant funding from the National Institute on Aging and the National Institute of Child Health and Human Development. Another author received grants from the Agency for Healthcare Research and Quality and the National Institute of Child Health and Human Development.

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

Women living in states that expanded Medicaid over the past decade were nearly 20% less likely to be hospitalized within 2 months of giving birth, according to a first-of-its-kind study published in Health Affairs.

Researchers analyzed patient records from eight states – four that expanded Medicaid insurance to include a broader swath of residents following the implementation of the Affordable Care Act, and four states that did not.

Hospitalizations in the 60 days after a woman gave birth fell by 17% in states that expanded Medicaid. The analysis also revealed an 8% drop in hospitalizations between 61 days and 6 months post partum.

“This is a very meaningful decline in hospitalization rates,” said Laura Wherry, PhD, a professor of economics and public service at New York University and a co-author of the study.

Women in states that chose not to expand Medicaid experienced a 7% increase in postpartum hospitalizations during that same time frame, the researchers report.

Many states raised income eligibility thresholds to 138% of the federal poverty level in 2014 with the implementation of the Affordable Care Act, which resulted in more coverage for low-income expectant mothers. To date, a dozen states have not implemented Medicaid expansion.

Dr. Wherry and her colleague wanted to take a closer look at outcomes for pregnant women during the postpartum period, both before and after states chose to expand Medicaid.

“A lot of prior work looking at the Medicaid program examined huge expansions to cover pregnant women during pregnancy, but often other periods of a woman’s life have been overlooked,” Dr. Wherry said. “What we were interested in is how that changed with the Affordable Care Act. You no longer needed to be pregnant to qualify.”

The researchers analyzed hospital discharge data between 2010 and 2017 before and after expansion in Iowa, Maryland, New Mexico, and Washington, which expanded coverage under Medicaid, and Florida, Georgia, Mississippi, and Utah, which did not do so.

Prior to 2014, fewer than 2% of births resulted in a postpartum hospitalization during the 60-day period in Medicaid expansion states. But in states that expanded Medicaid, hospitalizations decreased by 0.289 percentage points (P = .052), or 17% during the 60-day post-birth period.

Approximately 75% of the decline was attributed to diagnoses related to complications in pregnancy, childbirth, and the postpartum period.

Dr. Wherry said a variety of factors possibly drove down hospitalizations for new mothers who were able to obtain Medicaid coverage, including access to robust prenatal care, preconception counseling, and improved management of postpartum conditions outside the hospital.

The study provides a strategy for tackling the rising rate of maternal mortality in the United States, an increase largely attributed to postpartum deaths, said Lindsay Admon, MD, an ob.gyn. at the University of Michigan Medical School in Ann Arbor.

“This is one of the first studies showing or suggesting that Medicaid expansion not only led to improvements in Medicaid insurance but health outcomes as well,” said Dr. Admon, who is also researching maternal health and expanded Medicaid coverage.

Federal law has long required states to provide coverage for pregnant women up to 60 days post partum.

The 2021 American Rescue Act allowed states to extend coverage for pregnant women beyond the federal requirement to a year. More than half of states have chosen to do so. Since the study indicates that Medicaid expansion improves outcomes for these enrollees, Dr. Wherry and Dr. Admon said they hope state officials will consider the new findings during discussions to utilize the Rescue Act Coverage for pregnant women.

Dr. Wherry received support for the study from the Robert Wood Johnson Foundation Policies for Action Program and grant funding from the National Institute on Aging and the National Institute of Child Health and Human Development. Another author received grants from the Agency for Healthcare Research and Quality and the National Institute of Child Health and Human Development.

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

The largest combined analysis of birth outcome data for women with systemic lupus erythematosus (SLE) who took belimumab (Benlysta) during pregnancy appears to indicate that the biologic is “unlikely to cause very frequent birth defects,” but the full extent of possible risk remains unknown. The drug’s effect on B cells, immune function, and infections in exposed offspring were not captured in the data, but a separate case report published after the belimumab pregnancy data report indicates that the drug does cross the placenta and builds up in the blood of the newborn, reducing B cells at birth.

Children of women with SLE have increased birth defect risks, and standard SLE therapeutic agents (for example, cyclophosphamide, methotrexate, mycophenolate mofetil) have been implicated in birth defects and pregnancy loss, but birth defect data for biologic drugs such as belimumab are limited. While belimumab animal data revealed no evidence of fetal harm or pregnancy loss rates, there was evidence of immature and mature B-cell count reductions.

Belimumab is approved by the Food and Drug Administration for use in patients aged 5 years and older with active, autoantibody-positive SLE who are taking standard therapy, and also for those with lupus nephritis.

Michelle Petri, MD, of Johns Hopkins University, Baltimore, and coauthors reported in Annals of the Rheumatic Diseases on data they compiled through March 8, 2020, from belimumab clinical trials, the Belimumab Pregnancy Registry (BPR), and postmarketing/spontaneous reports that encompassed 319 pregnancies with known outcomes.

Across 18 clinical trials with 223 live births, birth defects occurred in 4 of 72 (5.6%) belimumab-exposed pregnancies and in 0 of 9 in placebo-exposed pregnancies. Pregnancy loss (excluding elective terminations) occurred in 31.8% (35 of 110) of belimumab-exposed women and 43.8% (7 of 16) of placebo-exposed women in clinical trials. In the BPR retrospective cohort, 4.2% had pregnancy loss. Postmarketing and spontaneous reports had a pregnancy loss rate of 31.4% (43 of 137). Concomitant medications, confounding factors, and/or missing data were noted in all belimumab-exposed women in clinical trials and the BPR cohort. Dr. Petri and colleagues reported no consistent pattern of birth defects across datasets but stated: “Low numbers of exposed pregnancies, presence of confounding factors/other biases, and incomplete information preclude informed recommendations regarding risk of birth defects and pregnancy loss with belimumab use.”

In an interview, coauthor Megan E. B. Clowse, MD, MPH, associate professor of medicine and director of the division of rheumatology and immunology at Duke University, Durham, N.C., said that “the Annals of the Rheumatic Diseases article provides some reassurance that belimumab is unlikely to cause very frequent birth defects. It is clearly not in the risk-range for thalidomide or mycophenolate. However, due to the complexity of collecting these data, this manuscript can’t explore the full extent of possible risks. It also did not provide information about B cells, immune function, or infection risks in exposed offspring.”

A separate case report by Helle Bitter of the department of rheumatology at Sorlandet Hospital Kristiansand (Norway) in Annals of the Rheumatic Diseases is the first to show transplacental passage of belimumab in humans. Other prior reports have shown such transplacental passage for monoclonal IgG antibodies (tumor necrosis factor inhibitors and rituximab). Even though the last infusion was given late in the second trimester, belimumab was present in cord serum at birth, suggesting much higher concentrations before treatment was stopped. While B-cell numbers were reduced at birth, they returned to normal ranges by 4 months post partum when they were undetectable. In the mother, B-cell numbers remained low throughout the study period extending to 7 months after delivery. The authors stated that the child had a normal vaccination response, and except for the reduced B-cell levels at birth, had no adverse effects of prenatal exposure to maternal medication through age 6 years.

“The belimumab transfer in the case report is the level that we would anticipate based on similar studies in infant/mother pairs on other IgG1 antibody biologics like adalimumab – about 60% higher than the maternal level at birth,” Dr. Clowse said. “That the baby has very low B cells at birth is worrisome to me, demonstrating the lasting effect of maternal belimumab on the infant’s immune system, even when the drug was stopped 14 weeks prior to delivery. While this single infant did not have problems with infections, with more widespread use it seems possible that infants would be found to have higher rates of infections after in utero belimumab exposure.”

The field of lupus research greatly needs controlled studies of newer biologics in pregnancy, Dr. Clowse said. “Women with active lupus in pregnancy – particularly with active lupus nephritis – continue to suffer tragic outcomes at an alarming rate. Newer treatments for lupus nephritis provide some hope that we might be able to control lupus nephritis in pregnancy more effectively. The available data suggests the risks of these medications are not so large as to make studies unreasonable. Our current data doesn’t allow us to sufficiently balance the potential risks and benefits in a way that provides clinically useful guidance. Trials of these medications, however, would enable us to identify improved treatment strategies that could result in healthier women, pregnancies, and babies.”

GlaxoSmithKline funded the study. Dr. Clowse reported receiving consulting fees and grants from UCB and GlaxoSmithKline that relate to pregnancy in women with lupus.

The largest combined analysis of birth outcome data for women with systemic lupus erythematosus (SLE) who took belimumab (Benlysta) during pregnancy appears to indicate that the biologic is “unlikely to cause very frequent birth defects,” but the full extent of possible risk remains unknown. The drug’s effect on B cells, immune function, and infections in exposed offspring were not captured in the data, but a separate case report published after the belimumab pregnancy data report indicates that the drug does cross the placenta and builds up in the blood of the newborn, reducing B cells at birth.

Children of women with SLE have increased birth defect risks, and standard SLE therapeutic agents (for example, cyclophosphamide, methotrexate, mycophenolate mofetil) have been implicated in birth defects and pregnancy loss, but birth defect data for biologic drugs such as belimumab are limited. While belimumab animal data revealed no evidence of fetal harm or pregnancy loss rates, there was evidence of immature and mature B-cell count reductions.

Belimumab is approved by the Food and Drug Administration for use in patients aged 5 years and older with active, autoantibody-positive SLE who are taking standard therapy, and also for those with lupus nephritis.

Michelle Petri, MD, of Johns Hopkins University, Baltimore, and coauthors reported in Annals of the Rheumatic Diseases on data they compiled through March 8, 2020, from belimumab clinical trials, the Belimumab Pregnancy Registry (BPR), and postmarketing/spontaneous reports that encompassed 319 pregnancies with known outcomes.

Across 18 clinical trials with 223 live births, birth defects occurred in 4 of 72 (5.6%) belimumab-exposed pregnancies and in 0 of 9 in placebo-exposed pregnancies. Pregnancy loss (excluding elective terminations) occurred in 31.8% (35 of 110) of belimumab-exposed women and 43.8% (7 of 16) of placebo-exposed women in clinical trials. In the BPR retrospective cohort, 4.2% had pregnancy loss. Postmarketing and spontaneous reports had a pregnancy loss rate of 31.4% (43 of 137). Concomitant medications, confounding factors, and/or missing data were noted in all belimumab-exposed women in clinical trials and the BPR cohort. Dr. Petri and colleagues reported no consistent pattern of birth defects across datasets but stated: “Low numbers of exposed pregnancies, presence of confounding factors/other biases, and incomplete information preclude informed recommendations regarding risk of birth defects and pregnancy loss with belimumab use.”

In an interview, coauthor Megan E. B. Clowse, MD, MPH, associate professor of medicine and director of the division of rheumatology and immunology at Duke University, Durham, N.C., said that “the Annals of the Rheumatic Diseases article provides some reassurance that belimumab is unlikely to cause very frequent birth defects. It is clearly not in the risk-range for thalidomide or mycophenolate. However, due to the complexity of collecting these data, this manuscript can’t explore the full extent of possible risks. It also did not provide information about B cells, immune function, or infection risks in exposed offspring.”

A separate case report by Helle Bitter of the department of rheumatology at Sorlandet Hospital Kristiansand (Norway) in Annals of the Rheumatic Diseases is the first to show transplacental passage of belimumab in humans. Other prior reports have shown such transplacental passage for monoclonal IgG antibodies (tumor necrosis factor inhibitors and rituximab). Even though the last infusion was given late in the second trimester, belimumab was present in cord serum at birth, suggesting much higher concentrations before treatment was stopped. While B-cell numbers were reduced at birth, they returned to normal ranges by 4 months post partum when they were undetectable. In the mother, B-cell numbers remained low throughout the study period extending to 7 months after delivery. The authors stated that the child had a normal vaccination response, and except for the reduced B-cell levels at birth, had no adverse effects of prenatal exposure to maternal medication through age 6 years.

“The belimumab transfer in the case report is the level that we would anticipate based on similar studies in infant/mother pairs on other IgG1 antibody biologics like adalimumab – about 60% higher than the maternal level at birth,” Dr. Clowse said. “That the baby has very low B cells at birth is worrisome to me, demonstrating the lasting effect of maternal belimumab on the infant’s immune system, even when the drug was stopped 14 weeks prior to delivery. While this single infant did not have problems with infections, with more widespread use it seems possible that infants would be found to have higher rates of infections after in utero belimumab exposure.”

The field of lupus research greatly needs controlled studies of newer biologics in pregnancy, Dr. Clowse said. “Women with active lupus in pregnancy – particularly with active lupus nephritis – continue to suffer tragic outcomes at an alarming rate. Newer treatments for lupus nephritis provide some hope that we might be able to control lupus nephritis in pregnancy more effectively. The available data suggests the risks of these medications are not so large as to make studies unreasonable. Our current data doesn’t allow us to sufficiently balance the potential risks and benefits in a way that provides clinically useful guidance. Trials of these medications, however, would enable us to identify improved treatment strategies that could result in healthier women, pregnancies, and babies.”

GlaxoSmithKline funded the study. Dr. Clowse reported receiving consulting fees and grants from UCB and GlaxoSmithKline that relate to pregnancy in women with lupus.

The largest combined analysis of birth outcome data for women with systemic lupus erythematosus (SLE) who took belimumab (Benlysta) during pregnancy appears to indicate that the biologic is “unlikely to cause very frequent birth defects,” but the full extent of possible risk remains unknown. The drug’s effect on B cells, immune function, and infections in exposed offspring were not captured in the data, but a separate case report published after the belimumab pregnancy data report indicates that the drug does cross the placenta and builds up in the blood of the newborn, reducing B cells at birth.

Children of women with SLE have increased birth defect risks, and standard SLE therapeutic agents (for example, cyclophosphamide, methotrexate, mycophenolate mofetil) have been implicated in birth defects and pregnancy loss, but birth defect data for biologic drugs such as belimumab are limited. While belimumab animal data revealed no evidence of fetal harm or pregnancy loss rates, there was evidence of immature and mature B-cell count reductions.

Belimumab is approved by the Food and Drug Administration for use in patients aged 5 years and older with active, autoantibody-positive SLE who are taking standard therapy, and also for those with lupus nephritis.

Michelle Petri, MD, of Johns Hopkins University, Baltimore, and coauthors reported in Annals of the Rheumatic Diseases on data they compiled through March 8, 2020, from belimumab clinical trials, the Belimumab Pregnancy Registry (BPR), and postmarketing/spontaneous reports that encompassed 319 pregnancies with known outcomes.

Across 18 clinical trials with 223 live births, birth defects occurred in 4 of 72 (5.6%) belimumab-exposed pregnancies and in 0 of 9 in placebo-exposed pregnancies. Pregnancy loss (excluding elective terminations) occurred in 31.8% (35 of 110) of belimumab-exposed women and 43.8% (7 of 16) of placebo-exposed women in clinical trials. In the BPR retrospective cohort, 4.2% had pregnancy loss. Postmarketing and spontaneous reports had a pregnancy loss rate of 31.4% (43 of 137). Concomitant medications, confounding factors, and/or missing data were noted in all belimumab-exposed women in clinical trials and the BPR cohort. Dr. Petri and colleagues reported no consistent pattern of birth defects across datasets but stated: “Low numbers of exposed pregnancies, presence of confounding factors/other biases, and incomplete information preclude informed recommendations regarding risk of birth defects and pregnancy loss with belimumab use.”

In an interview, coauthor Megan E. B. Clowse, MD, MPH, associate professor of medicine and director of the division of rheumatology and immunology at Duke University, Durham, N.C., said that “the Annals of the Rheumatic Diseases article provides some reassurance that belimumab is unlikely to cause very frequent birth defects. It is clearly not in the risk-range for thalidomide or mycophenolate. However, due to the complexity of collecting these data, this manuscript can’t explore the full extent of possible risks. It also did not provide information about B cells, immune function, or infection risks in exposed offspring.”

A separate case report by Helle Bitter of the department of rheumatology at Sorlandet Hospital Kristiansand (Norway) in Annals of the Rheumatic Diseases is the first to show transplacental passage of belimumab in humans. Other prior reports have shown such transplacental passage for monoclonal IgG antibodies (tumor necrosis factor inhibitors and rituximab). Even though the last infusion was given late in the second trimester, belimumab was present in cord serum at birth, suggesting much higher concentrations before treatment was stopped. While B-cell numbers were reduced at birth, they returned to normal ranges by 4 months post partum when they were undetectable. In the mother, B-cell numbers remained low throughout the study period extending to 7 months after delivery. The authors stated that the child had a normal vaccination response, and except for the reduced B-cell levels at birth, had no adverse effects of prenatal exposure to maternal medication through age 6 years.

“The belimumab transfer in the case report is the level that we would anticipate based on similar studies in infant/mother pairs on other IgG1 antibody biologics like adalimumab – about 60% higher than the maternal level at birth,” Dr. Clowse said. “That the baby has very low B cells at birth is worrisome to me, demonstrating the lasting effect of maternal belimumab on the infant’s immune system, even when the drug was stopped 14 weeks prior to delivery. While this single infant did not have problems with infections, with more widespread use it seems possible that infants would be found to have higher rates of infections after in utero belimumab exposure.”

The field of lupus research greatly needs controlled studies of newer biologics in pregnancy, Dr. Clowse said. “Women with active lupus in pregnancy – particularly with active lupus nephritis – continue to suffer tragic outcomes at an alarming rate. Newer treatments for lupus nephritis provide some hope that we might be able to control lupus nephritis in pregnancy more effectively. The available data suggests the risks of these medications are not so large as to make studies unreasonable. Our current data doesn’t allow us to sufficiently balance the potential risks and benefits in a way that provides clinically useful guidance. Trials of these medications, however, would enable us to identify improved treatment strategies that could result in healthier women, pregnancies, and babies.”

GlaxoSmithKline funded the study. Dr. Clowse reported receiving consulting fees and grants from UCB and GlaxoSmithKline that relate to pregnancy in women with lupus.

CASE Pregnant patient with concerning symptoms of infection

A 28-year-old primigravid woman at 26 weeks’ gestation requests evaluation because of a 3-day history of low-grade fever (38.3 °C), chills, malaise, myalgias, pain in her upper back, nausea, diarrhea, and intermittent uterine contractions. Her symptoms began 2 days after she and her husband dined at a local Mexican restaurant. She specifically recalls eating unpasteurized cheese (queso fresco). Her husband also is experiencing similar symptoms.

• What is the most likely diagnosis?
• What tests should be performed to confirm the diagnosis?
• Does this infection pose a risk to the fetus?
• How should this patient be treated?

Listeriosis, a potentially serious foodborne illness, is an unusual infection in pregnancy. It can cause a number of adverse effects in both the pregnant woman and her fetus, including fetal death in utero. In this article, we review the microbiology and epidemiology of Listeria infection, consider the important steps in diagnosis, and discuss treatment options and prevention measures.

The causative organism in listeriosis

Listeriosis is caused by Listeria monocytogenes, a gram-positive, non–spore-forming bacillus. The organism is catalase positive and oxidase negative, and it exhibits tumbling motility when grown in culture. It can grow at temperatures less than 4 °C, which facilitates foodborne transmission of the bacterium despite adequate refrigeration. Of the 13 serotypes of L monocytogenes, the 1/2a, 1/2b, and 4b are most likely to be associated with human infection. The major virulence factors of L monocytogenes are the internalin surface proteins and the pore-forming listeriolysin O (LLO) cytotoxin. These factors enable the organism to effectively invade host cells.¹

The pathogen uses several mechanisms to evade gastrointestinal defenses prior to entry into the bloodstream. It avoids destruction in the stomach by using proton pump inhibitors to elevate the pH of gastric acid. In the duodenum, it survives the antibacterial properties of bile by secreting bile salt hydrolases, which catabolize bile salts. In addition, the cytotoxin listeriolysin S (LLS) disrupts the protective barrier created by the normal gut flora. Once the organism penetrates the gastrointestinal barriers, it disseminates through the blood and lymphatics and then infects other tissues, such as the brain and placenta.^1,2

Pathogenesis of infection

The primary reservoir of Listeria is soil and decaying vegetable matter. The organism also has been isolated from animal feed, water, sewage, and many animal species. With rare exceptions, most infections in adults result from inadvertent ingestion of the organism in contaminated food. In certain high-risk occupations, such as veterinary medicine, farming, and laboratory work, infection of the skin or eye can result from direct contact with an infected animal.³

Of note, foodborne illness caused by Listeria has the third highest mortality rate of any foodborne infection, 16% compared with 35% for Vibrio vulnificus and 17% for Clostridium botulinum.^2,3 The principal foods that have been linked to listeriosis include:

• soft cheeses, particularly those made from unpasteurized milk
• melon
• hot dogs
• lunch meat, such as bologna
• deli meat, especially chicken
• canned foods, such as smoked seafood, and pâté or meat spreads that are labeled “keep refrigerated”
• unpasteurized milk
• sprouts
• hummus.

In healthy adults, listeriosis is usually a short-lived illness. However, in older adults, immunocompromised patients, and pregnant women, the infection can be devastating. Infection in the pregnant woman also poses major danger to the developing fetus because the organism has a special predilection for placental and fetal tissue.^1,3,4

Immunity to Listeria infection depends primarily on T-cell lymphokine activation of macrophages. These latter cells are responsible for clearing the bacterium from the blood. As noted above, the principal virulence factor of L monocytogenes is listeriolysin O, a cholesterol-dependent cytolysin. This substance induces T-cell receptor unresponsiveness, thus interfering with the host immune response to the invading pathogen.^1,3-5

Continue to: Clinical manifestations of listeriosis...

Listeria infections may present with various manifestations, depending on the degree of exposure and the underlying immunocompetence of the host (FIGURE). In its most common and simplest form, listeriosis presents as a mild to moderate gastroenteritis following exposure to contaminated food. Symptoms typically develop within 24 hours of exposure and include fever, myalgias, abdominal or back pain, nausea, vomiting, and diarrhea.⁵

Conversely, in immunocompromised patients, including pregnant women, listeriosis can present as life-threatening sepsis and/or central nervous system (CNS) infection (invasive infection). In this clinical setting, the mean incubation period is 11 days. The manifestations of CNS infection include meningoencephalitis, cerebritis, rhombencephalitis (infection and inflammation of the brain stem), brain abscess, and spinal cord abscess.⁵

In addition to these 2 clinical presentations, listeriosis can cause unusual focal infections as illustrated in the FIGURE. Some of these infections have unique clinical associations. For example, skin or eye infections may occur as a result of direct inoculation in veterinarians, farmers, and laboratory workers. Listeria peritonitis may occur in patients who are receiving peritoneal dialysis and in those who have cirrhosis. Prosthetic joint and graft infections, of course, may occur in patients who have had invasive procedures for implantation of grafts or prosthetic devices.⁵

Listeriosis is especially dangerous in pregnancy because it not only can cause serious injury to the mother and even death but it also may pose a major risk to fetal well-being. Possible perinatal complications include fetal death; preterm labor and delivery; and neonatal sepsis, meningitis, and death.^5-8

Making the diagnosis

Diagnosis begins with a thorough and focused history to assess for characteristic symptoms and possible Listeria exposure. Exposure should be presumed for patients who report consuming high-risk foods, especially foods recently recalled by the US Food and Drug Administration.

In the asymptomatic pregnant patient, diagnostic testing can be deferred, and the patient should be instructed to return for evaluation if symptoms develop within 2 months of exposure. However, symptomatic, febrile patients require testing. The most valuable testing modality is Gram stain and culture of blood. Gram stain typically will show gram-positive pleomorphic rods with rounded ends. Amniocentesis may be indicated if blood cultures are not definitive. Meconium staining of the amniotic fluid and a positive Gram stain are highly indicative of fetal infection. Cultures of the cerebrospinal fluid are indicated in any individual with focal neurologic findings. Stool cultures are rarely indicated.

When obtaining any of the cultures noted above, the clinician should alert the microbiologist of the concern for listeriosis because L monocytogenes can be confused with common contaminants, such as diphtheroids.^5-9

Treatment and follow-up

The treatment of listeriosis in pregnancy depends on the severity of the infection and the immune status of the mother. The TABLE offers several different clinical scenarios and the appropriate treatment for each. As noted, several scenarios may require cultures of the blood, cerebrospinal fluid, and amniotic fluid.^7,9,10

Following treatment of the mother, serial ultrasound examinations should be performed to monitor fetal growth, CNS anatomy, placental morphology, amniotic fluid volume, and umbilical artery Doppler velocimetry. In the presence of fetal growth restriction, oligohydramnios, or abnormal Doppler velocimetry, biophysical profile testing should be performed. After delivery, the placenta should be examined carefully for histologic evidence of Listeria infection, such as miliary abscesses, and cultured for the bacterium.^7-9

Prevention measures

Conservative measures for prevention of Listeria infection in pregnant women include the following^7,10-12:

• Refrigerate milk and milk products at 40 °F (4.4 °C).
• Thoroughly cook raw food from animal sources.
• Wash raw vegetables carefully before eating.
• Keep uncooked meats separate from cooked meats and vegetables.
• Do not consume any beverages or foods made from unpasteurized milk.
• After handling uncooked foods, carefully wash all utensils and hands.
• Avoid all soft cheeses, such as Mexican-style feta, Brie, Camembert, and blue cheese, even if they are supposedly made from pasteurized milk.
• Reheat until steaming hot all leftover foods or ready-to-eat foods, such as hot dogs.
• Do not let juice from hot dogs or lunch meat packages drip onto other foods, utensils, or food preparation surfaces.
• Do not store opened hot dog packages in the refrigerator for more than 1 week. Do not store unopened packages for longer than 2 weeks.
• Do not store unopened lunch and deli meat packages in the refrigerator for longer than 2 weeks. Do not store opened packages for longer than 3 to 5 days.
• If other immunosuppressive conditions are present in combination with pregnancy, thoroughly heat cold cuts before eating.
• Do not eat raw or even lightly cooked sprouts of any kind. Cook sprouts thoroughly. Rinsing sprouts will not remove Listeria organisms.
• Do not eat refrigerated pâté or meat spreads from a deli counter or the refrigerated section of a grocery store.
• Canned or shelf-stable pâté and meat spreads are safe to eat, but be sure to refrigerate them after opening the packages.
• Do not eat refrigerated smoked seafood. Canned or shelf-stable seafood, particularly when incorporated into a casserole, is safe to eat.
• Eat cut melon immediately. Refrigerate uneaten melon quickly if not eaten. Discard cut melon that is left at room temperature for more than 4 hours.

CASE Diagnosis made and prompt treatment initiated

The most likely diagnosis in this patient is listeriosis. Because the patient is moderately ill and experiencing uterine contractions, she should be hospitalized and monitored for progressive cervical dilation. Blood cultures should be obtained to identify L monocytogenes. In addition, an amniocentesis should be performed, and the amniotic fluid should be cultured for this microorganism. Stool culture and culture of the cerebrospinal fluid are not indicated. The patient should be treated with intravenous ampicillin, 2 g every 4 hours for 14 days. If she is allergic to penicillin, the alternative drug is trimethoprim-sulfamethoxazole, 8 to 10 mg/kg per day in 2 divided doses, for 14 days. Prompt and effective treatment of the mother should prevent infection in the fetus and newborn. ●

CASE Pregnant patient with concerning symptoms of infection

A 28-year-old primigravid woman at 26 weeks’ gestation requests evaluation because of a 3-day history of low-grade fever (38.3 °C), chills, malaise, myalgias, pain in her upper back, nausea, diarrhea, and intermittent uterine contractions. Her symptoms began 2 days after she and her husband dined at a local Mexican restaurant. She specifically recalls eating unpasteurized cheese (queso fresco). Her husband also is experiencing similar symptoms.

• What is the most likely diagnosis?
• What tests should be performed to confirm the diagnosis?
• Does this infection pose a risk to the fetus?
• How should this patient be treated?

Listeriosis, a potentially serious foodborne illness, is an unusual infection in pregnancy. It can cause a number of adverse effects in both the pregnant woman and her fetus, including fetal death in utero. In this article, we review the microbiology and epidemiology of Listeria infection, consider the important steps in diagnosis, and discuss treatment options and prevention measures.

The causative organism in listeriosis

Listeriosis is caused by Listeria monocytogenes, a gram-positive, non–spore-forming bacillus. The organism is catalase positive and oxidase negative, and it exhibits tumbling motility when grown in culture. It can grow at temperatures less than 4 °C, which facilitates foodborne transmission of the bacterium despite adequate refrigeration. Of the 13 serotypes of L monocytogenes, the 1/2a, 1/2b, and 4b are most likely to be associated with human infection. The major virulence factors of L monocytogenes are the internalin surface proteins and the pore-forming listeriolysin O (LLO) cytotoxin. These factors enable the organism to effectively invade host cells.¹

The pathogen uses several mechanisms to evade gastrointestinal defenses prior to entry into the bloodstream. It avoids destruction in the stomach by using proton pump inhibitors to elevate the pH of gastric acid. In the duodenum, it survives the antibacterial properties of bile by secreting bile salt hydrolases, which catabolize bile salts. In addition, the cytotoxin listeriolysin S (LLS) disrupts the protective barrier created by the normal gut flora. Once the organism penetrates the gastrointestinal barriers, it disseminates through the blood and lymphatics and then infects other tissues, such as the brain and placenta.^1,2

Pathogenesis of infection

The primary reservoir of Listeria is soil and decaying vegetable matter. The organism also has been isolated from animal feed, water, sewage, and many animal species. With rare exceptions, most infections in adults result from inadvertent ingestion of the organism in contaminated food. In certain high-risk occupations, such as veterinary medicine, farming, and laboratory work, infection of the skin or eye can result from direct contact with an infected animal.³

Of note, foodborne illness caused by Listeria has the third highest mortality rate of any foodborne infection, 16% compared with 35% for Vibrio vulnificus and 17% for Clostridium botulinum.^2,3 The principal foods that have been linked to listeriosis include:

• soft cheeses, particularly those made from unpasteurized milk
• melon
• hot dogs
• lunch meat, such as bologna
• deli meat, especially chicken
• canned foods, such as smoked seafood, and pâté or meat spreads that are labeled “keep refrigerated”
• unpasteurized milk
• sprouts
• hummus.

In healthy adults, listeriosis is usually a short-lived illness. However, in older adults, immunocompromised patients, and pregnant women, the infection can be devastating. Infection in the pregnant woman also poses major danger to the developing fetus because the organism has a special predilection for placental and fetal tissue.^1,3,4

Immunity to Listeria infection depends primarily on T-cell lymphokine activation of macrophages. These latter cells are responsible for clearing the bacterium from the blood. As noted above, the principal virulence factor of L monocytogenes is listeriolysin O, a cholesterol-dependent cytolysin. This substance induces T-cell receptor unresponsiveness, thus interfering with the host immune response to the invading pathogen.^1,3-5

Continue to: Clinical manifestations of listeriosis...

Listeria infections may present with various manifestations, depending on the degree of exposure and the underlying immunocompetence of the host (FIGURE). In its most common and simplest form, listeriosis presents as a mild to moderate gastroenteritis following exposure to contaminated food. Symptoms typically develop within 24 hours of exposure and include fever, myalgias, abdominal or back pain, nausea, vomiting, and diarrhea.⁵

Conversely, in immunocompromised patients, including pregnant women, listeriosis can present as life-threatening sepsis and/or central nervous system (CNS) infection (invasive infection). In this clinical setting, the mean incubation period is 11 days. The manifestations of CNS infection include meningoencephalitis, cerebritis, rhombencephalitis (infection and inflammation of the brain stem), brain abscess, and spinal cord abscess.⁵

In addition to these 2 clinical presentations, listeriosis can cause unusual focal infections as illustrated in the FIGURE. Some of these infections have unique clinical associations. For example, skin or eye infections may occur as a result of direct inoculation in veterinarians, farmers, and laboratory workers. Listeria peritonitis may occur in patients who are receiving peritoneal dialysis and in those who have cirrhosis. Prosthetic joint and graft infections, of course, may occur in patients who have had invasive procedures for implantation of grafts or prosthetic devices.⁵

Listeriosis is especially dangerous in pregnancy because it not only can cause serious injury to the mother and even death but it also may pose a major risk to fetal well-being. Possible perinatal complications include fetal death; preterm labor and delivery; and neonatal sepsis, meningitis, and death.^5-8

Making the diagnosis

Diagnosis begins with a thorough and focused history to assess for characteristic symptoms and possible Listeria exposure. Exposure should be presumed for patients who report consuming high-risk foods, especially foods recently recalled by the US Food and Drug Administration.

In the asymptomatic pregnant patient, diagnostic testing can be deferred, and the patient should be instructed to return for evaluation if symptoms develop within 2 months of exposure. However, symptomatic, febrile patients require testing. The most valuable testing modality is Gram stain and culture of blood. Gram stain typically will show gram-positive pleomorphic rods with rounded ends. Amniocentesis may be indicated if blood cultures are not definitive. Meconium staining of the amniotic fluid and a positive Gram stain are highly indicative of fetal infection. Cultures of the cerebrospinal fluid are indicated in any individual with focal neurologic findings. Stool cultures are rarely indicated.

When obtaining any of the cultures noted above, the clinician should alert the microbiologist of the concern for listeriosis because L monocytogenes can be confused with common contaminants, such as diphtheroids.^5-9

Treatment and follow-up

The treatment of listeriosis in pregnancy depends on the severity of the infection and the immune status of the mother. The TABLE offers several different clinical scenarios and the appropriate treatment for each. As noted, several scenarios may require cultures of the blood, cerebrospinal fluid, and amniotic fluid.^7,9,10

Following treatment of the mother, serial ultrasound examinations should be performed to monitor fetal growth, CNS anatomy, placental morphology, amniotic fluid volume, and umbilical artery Doppler velocimetry. In the presence of fetal growth restriction, oligohydramnios, or abnormal Doppler velocimetry, biophysical profile testing should be performed. After delivery, the placenta should be examined carefully for histologic evidence of Listeria infection, such as miliary abscesses, and cultured for the bacterium.^7-9

Prevention measures

Conservative measures for prevention of Listeria infection in pregnant women include the following^7,10-12:

• Refrigerate milk and milk products at 40 °F (4.4 °C).
• Thoroughly cook raw food from animal sources.
• Wash raw vegetables carefully before eating.
• Keep uncooked meats separate from cooked meats and vegetables.
• Do not consume any beverages or foods made from unpasteurized milk.
• After handling uncooked foods, carefully wash all utensils and hands.
• Avoid all soft cheeses, such as Mexican-style feta, Brie, Camembert, and blue cheese, even if they are supposedly made from pasteurized milk.
• Reheat until steaming hot all leftover foods or ready-to-eat foods, such as hot dogs.
• Do not let juice from hot dogs or lunch meat packages drip onto other foods, utensils, or food preparation surfaces.
• Do not store opened hot dog packages in the refrigerator for more than 1 week. Do not store unopened packages for longer than 2 weeks.
• Do not store unopened lunch and deli meat packages in the refrigerator for longer than 2 weeks. Do not store opened packages for longer than 3 to 5 days.
• If other immunosuppressive conditions are present in combination with pregnancy, thoroughly heat cold cuts before eating.
• Do not eat raw or even lightly cooked sprouts of any kind. Cook sprouts thoroughly. Rinsing sprouts will not remove Listeria organisms.
• Do not eat refrigerated pâté or meat spreads from a deli counter or the refrigerated section of a grocery store.
• Canned or shelf-stable pâté and meat spreads are safe to eat, but be sure to refrigerate them after opening the packages.
• Do not eat refrigerated smoked seafood. Canned or shelf-stable seafood, particularly when incorporated into a casserole, is safe to eat.
• Eat cut melon immediately. Refrigerate uneaten melon quickly if not eaten. Discard cut melon that is left at room temperature for more than 4 hours.

CASE Diagnosis made and prompt treatment initiated

The most likely diagnosis in this patient is listeriosis. Because the patient is moderately ill and experiencing uterine contractions, she should be hospitalized and monitored for progressive cervical dilation. Blood cultures should be obtained to identify L monocytogenes. In addition, an amniocentesis should be performed, and the amniotic fluid should be cultured for this microorganism. Stool culture and culture of the cerebrospinal fluid are not indicated. The patient should be treated with intravenous ampicillin, 2 g every 4 hours for 14 days. If she is allergic to penicillin, the alternative drug is trimethoprim-sulfamethoxazole, 8 to 10 mg/kg per day in 2 divided doses, for 14 days. Prompt and effective treatment of the mother should prevent infection in the fetus and newborn. ●

CASE Pregnant patient with concerning symptoms of infection

A 28-year-old primigravid woman at 26 weeks’ gestation requests evaluation because of a 3-day history of low-grade fever (38.3 °C), chills, malaise, myalgias, pain in her upper back, nausea, diarrhea, and intermittent uterine contractions. Her symptoms began 2 days after she and her husband dined at a local Mexican restaurant. She specifically recalls eating unpasteurized cheese (queso fresco). Her husband also is experiencing similar symptoms.

• What is the most likely diagnosis?
• What tests should be performed to confirm the diagnosis?
• Does this infection pose a risk to the fetus?
• How should this patient be treated?

Listeriosis, a potentially serious foodborne illness, is an unusual infection in pregnancy. It can cause a number of adverse effects in both the pregnant woman and her fetus, including fetal death in utero. In this article, we review the microbiology and epidemiology of Listeria infection, consider the important steps in diagnosis, and discuss treatment options and prevention measures.

The causative organism in listeriosis

Listeriosis is caused by Listeria monocytogenes, a gram-positive, non–spore-forming bacillus. The organism is catalase positive and oxidase negative, and it exhibits tumbling motility when grown in culture. It can grow at temperatures less than 4 °C, which facilitates foodborne transmission of the bacterium despite adequate refrigeration. Of the 13 serotypes of L monocytogenes, the 1/2a, 1/2b, and 4b are most likely to be associated with human infection. The major virulence factors of L monocytogenes are the internalin surface proteins and the pore-forming listeriolysin O (LLO) cytotoxin. These factors enable the organism to effectively invade host cells.¹

The pathogen uses several mechanisms to evade gastrointestinal defenses prior to entry into the bloodstream. It avoids destruction in the stomach by using proton pump inhibitors to elevate the pH of gastric acid. In the duodenum, it survives the antibacterial properties of bile by secreting bile salt hydrolases, which catabolize bile salts. In addition, the cytotoxin listeriolysin S (LLS) disrupts the protective barrier created by the normal gut flora. Once the organism penetrates the gastrointestinal barriers, it disseminates through the blood and lymphatics and then infects other tissues, such as the brain and placenta.^1,2

Pathogenesis of infection

The primary reservoir of Listeria is soil and decaying vegetable matter. The organism also has been isolated from animal feed, water, sewage, and many animal species. With rare exceptions, most infections in adults result from inadvertent ingestion of the organism in contaminated food. In certain high-risk occupations, such as veterinary medicine, farming, and laboratory work, infection of the skin or eye can result from direct contact with an infected animal.³

Of note, foodborne illness caused by Listeria has the third highest mortality rate of any foodborne infection, 16% compared with 35% for Vibrio vulnificus and 17% for Clostridium botulinum.^2,3 The principal foods that have been linked to listeriosis include:

• soft cheeses, particularly those made from unpasteurized milk
• melon
• hot dogs
• lunch meat, such as bologna
• deli meat, especially chicken
• canned foods, such as smoked seafood, and pâté or meat spreads that are labeled “keep refrigerated”
• unpasteurized milk
• sprouts
• hummus.

In healthy adults, listeriosis is usually a short-lived illness. However, in older adults, immunocompromised patients, and pregnant women, the infection can be devastating. Infection in the pregnant woman also poses major danger to the developing fetus because the organism has a special predilection for placental and fetal tissue.^1,3,4

Immunity to Listeria infection depends primarily on T-cell lymphokine activation of macrophages. These latter cells are responsible for clearing the bacterium from the blood. As noted above, the principal virulence factor of L monocytogenes is listeriolysin O, a cholesterol-dependent cytolysin. This substance induces T-cell receptor unresponsiveness, thus interfering with the host immune response to the invading pathogen.^1,3-5

Continue to: Clinical manifestations of listeriosis...

Listeria infections may present with various manifestations, depending on the degree of exposure and the underlying immunocompetence of the host (FIGURE). In its most common and simplest form, listeriosis presents as a mild to moderate gastroenteritis following exposure to contaminated food. Symptoms typically develop within 24 hours of exposure and include fever, myalgias, abdominal or back pain, nausea, vomiting, and diarrhea.⁵

Conversely, in immunocompromised patients, including pregnant women, listeriosis can present as life-threatening sepsis and/or central nervous system (CNS) infection (invasive infection). In this clinical setting, the mean incubation period is 11 days. The manifestations of CNS infection include meningoencephalitis, cerebritis, rhombencephalitis (infection and inflammation of the brain stem), brain abscess, and spinal cord abscess.⁵

In addition to these 2 clinical presentations, listeriosis can cause unusual focal infections as illustrated in the FIGURE. Some of these infections have unique clinical associations. For example, skin or eye infections may occur as a result of direct inoculation in veterinarians, farmers, and laboratory workers. Listeria peritonitis may occur in patients who are receiving peritoneal dialysis and in those who have cirrhosis. Prosthetic joint and graft infections, of course, may occur in patients who have had invasive procedures for implantation of grafts or prosthetic devices.⁵

Listeriosis is especially dangerous in pregnancy because it not only can cause serious injury to the mother and even death but it also may pose a major risk to fetal well-being. Possible perinatal complications include fetal death; preterm labor and delivery; and neonatal sepsis, meningitis, and death.^5-8

Making the diagnosis

Diagnosis begins with a thorough and focused history to assess for characteristic symptoms and possible Listeria exposure. Exposure should be presumed for patients who report consuming high-risk foods, especially foods recently recalled by the US Food and Drug Administration.

In the asymptomatic pregnant patient, diagnostic testing can be deferred, and the patient should be instructed to return for evaluation if symptoms develop within 2 months of exposure. However, symptomatic, febrile patients require testing. The most valuable testing modality is Gram stain and culture of blood. Gram stain typically will show gram-positive pleomorphic rods with rounded ends. Amniocentesis may be indicated if blood cultures are not definitive. Meconium staining of the amniotic fluid and a positive Gram stain are highly indicative of fetal infection. Cultures of the cerebrospinal fluid are indicated in any individual with focal neurologic findings. Stool cultures are rarely indicated.

When obtaining any of the cultures noted above, the clinician should alert the microbiologist of the concern for listeriosis because L monocytogenes can be confused with common contaminants, such as diphtheroids.^5-9

Treatment and follow-up

The treatment of listeriosis in pregnancy depends on the severity of the infection and the immune status of the mother. The TABLE offers several different clinical scenarios and the appropriate treatment for each. As noted, several scenarios may require cultures of the blood, cerebrospinal fluid, and amniotic fluid.^7,9,10

Following treatment of the mother, serial ultrasound examinations should be performed to monitor fetal growth, CNS anatomy, placental morphology, amniotic fluid volume, and umbilical artery Doppler velocimetry. In the presence of fetal growth restriction, oligohydramnios, or abnormal Doppler velocimetry, biophysical profile testing should be performed. After delivery, the placenta should be examined carefully for histologic evidence of Listeria infection, such as miliary abscesses, and cultured for the bacterium.^7-9

Prevention measures

Conservative measures for prevention of Listeria infection in pregnant women include the following^7,10-12:

• Refrigerate milk and milk products at 40 °F (4.4 °C).
• Thoroughly cook raw food from animal sources.
• Wash raw vegetables carefully before eating.
• Keep uncooked meats separate from cooked meats and vegetables.
• Do not consume any beverages or foods made from unpasteurized milk.
• After handling uncooked foods, carefully wash all utensils and hands.
• Avoid all soft cheeses, such as Mexican-style feta, Brie, Camembert, and blue cheese, even if they are supposedly made from pasteurized milk.
• Reheat until steaming hot all leftover foods or ready-to-eat foods, such as hot dogs.
• Do not let juice from hot dogs or lunch meat packages drip onto other foods, utensils, or food preparation surfaces.
• Do not store opened hot dog packages in the refrigerator for more than 1 week. Do not store unopened packages for longer than 2 weeks.
• Do not store unopened lunch and deli meat packages in the refrigerator for longer than 2 weeks. Do not store opened packages for longer than 3 to 5 days.
• If other immunosuppressive conditions are present in combination with pregnancy, thoroughly heat cold cuts before eating.
• Do not eat raw or even lightly cooked sprouts of any kind. Cook sprouts thoroughly. Rinsing sprouts will not remove Listeria organisms.
• Do not eat refrigerated pâté or meat spreads from a deli counter or the refrigerated section of a grocery store.
• Canned or shelf-stable pâté and meat spreads are safe to eat, but be sure to refrigerate them after opening the packages.
• Do not eat refrigerated smoked seafood. Canned or shelf-stable seafood, particularly when incorporated into a casserole, is safe to eat.
• Eat cut melon immediately. Refrigerate uneaten melon quickly if not eaten. Discard cut melon that is left at room temperature for more than 4 hours.

CASE Diagnosis made and prompt treatment initiated

The most likely diagnosis in this patient is listeriosis. Because the patient is moderately ill and experiencing uterine contractions, she should be hospitalized and monitored for progressive cervical dilation. Blood cultures should be obtained to identify L monocytogenes. In addition, an amniocentesis should be performed, and the amniotic fluid should be cultured for this microorganism. Stool culture and culture of the cerebrospinal fluid are not indicated. The patient should be treated with intravenous ampicillin, 2 g every 4 hours for 14 days. If she is allergic to penicillin, the alternative drug is trimethoprim-sulfamethoxazole, 8 to 10 mg/kg per day in 2 divided doses, for 14 days. Prompt and effective treatment of the mother should prevent infection in the fetus and newborn. ●