Obstetrics

A multicenter, international phase 2 trial known as EDELIFE is underway to investigate the safety and efficacy of an in utero treatment for developing males with X-linked hypohidrotic ectodermal dysplasia (XLHED).

This condition is caused by mutations in the gene coding for ectodysplasin A (EDA), a protein that signals the epithelial-mesenchymal transition during embryogenesis. EDA loss or dysfunction precludes binding to its endogenous EDA1 receptor (EDAR), and downstream development of teeth, hair, nails, and skin adnexae, most notably eccrine glands.

shironosov/Getty Images

The treatment, ER004, is a first-in-class signaling protein EDA replacement molecule now under investigation by the EspeRare Foundation, with support from the Pierre Fabre Foundation. The pioneering clinical trial is evaluating the delivery of ER004 protein replacement in utero to affected fetuses, allowing antenatal binding to the EDAR. According to the EDELIFE web site, when ER004 is administered to XLHED-affected males in utero, it “should act as a replacement for the missing EDA and trigger the process that leads to the normal development of a baby’s skin, teeth, hair, and sweat glands, leading to better formation of these structures.”

The protein is delivered into the amniotic fluid via a needle and syringe under ultrasound guidance. In a report on this treatment used in a pair of affected twins and a third XLHED-affected male published in 2018, the authors reported that the three babies were able to sweat normally after birth, “and XLHED-related illness had not developed by 14-22 months of age.”

The goal of the prospective, open-label, genotype match–controlled EDELIFE trial is to confirm the efficacy and safety results for ER004 in a larger group of boys, and to determine if it can lead to robust, and long-lasting improvement in XLHED-associated defects.

In the United States, the first pregnant woman to join the study received the treatment in February 2023 at Washington University in St. Louis. Other clinical sites are located in France, Germany, Italy, Spain, and the United Kingdom. Led by principal investigator Holm Schneider, MD, of the University Erlanger-Nurnberg (Germany), researchers are seeking to enroll mothers aged 18 years and older who are genetically confirmed carriers of the XLHED mutation and pregnant with a boy or considering pregnancy. The control group will include XLHED-affected males, 6 months to 60 years old, who are blood relatives of the pregnant woman participating in the study.

Clinicians treating affected families or potentially eligible subjects are encouraged to contact the trial investigators at this link.

A multicenter, international phase 2 trial known as EDELIFE is underway to investigate the safety and efficacy of an in utero treatment for developing males with X-linked hypohidrotic ectodermal dysplasia (XLHED).

This condition is caused by mutations in the gene coding for ectodysplasin A (EDA), a protein that signals the epithelial-mesenchymal transition during embryogenesis. EDA loss or dysfunction precludes binding to its endogenous EDA1 receptor (EDAR), and downstream development of teeth, hair, nails, and skin adnexae, most notably eccrine glands.

shironosov/Getty Images

The treatment, ER004, is a first-in-class signaling protein EDA replacement molecule now under investigation by the EspeRare Foundation, with support from the Pierre Fabre Foundation. The pioneering clinical trial is evaluating the delivery of ER004 protein replacement in utero to affected fetuses, allowing antenatal binding to the EDAR. According to the EDELIFE web site, when ER004 is administered to XLHED-affected males in utero, it “should act as a replacement for the missing EDA and trigger the process that leads to the normal development of a baby’s skin, teeth, hair, and sweat glands, leading to better formation of these structures.”

The protein is delivered into the amniotic fluid via a needle and syringe under ultrasound guidance. In a report on this treatment used in a pair of affected twins and a third XLHED-affected male published in 2018, the authors reported that the three babies were able to sweat normally after birth, “and XLHED-related illness had not developed by 14-22 months of age.”

The goal of the prospective, open-label, genotype match–controlled EDELIFE trial is to confirm the efficacy and safety results for ER004 in a larger group of boys, and to determine if it can lead to robust, and long-lasting improvement in XLHED-associated defects.

In the United States, the first pregnant woman to join the study received the treatment in February 2023 at Washington University in St. Louis. Other clinical sites are located in France, Germany, Italy, Spain, and the United Kingdom. Led by principal investigator Holm Schneider, MD, of the University Erlanger-Nurnberg (Germany), researchers are seeking to enroll mothers aged 18 years and older who are genetically confirmed carriers of the XLHED mutation and pregnant with a boy or considering pregnancy. The control group will include XLHED-affected males, 6 months to 60 years old, who are blood relatives of the pregnant woman participating in the study.

Clinicians treating affected families or potentially eligible subjects are encouraged to contact the trial investigators at this link.

A multicenter, international phase 2 trial known as EDELIFE is underway to investigate the safety and efficacy of an in utero treatment for developing males with X-linked hypohidrotic ectodermal dysplasia (XLHED).

This condition is caused by mutations in the gene coding for ectodysplasin A (EDA), a protein that signals the epithelial-mesenchymal transition during embryogenesis. EDA loss or dysfunction precludes binding to its endogenous EDA1 receptor (EDAR), and downstream development of teeth, hair, nails, and skin adnexae, most notably eccrine glands.

shironosov/Getty Images

The treatment, ER004, is a first-in-class signaling protein EDA replacement molecule now under investigation by the EspeRare Foundation, with support from the Pierre Fabre Foundation. The pioneering clinical trial is evaluating the delivery of ER004 protein replacement in utero to affected fetuses, allowing antenatal binding to the EDAR. According to the EDELIFE web site, when ER004 is administered to XLHED-affected males in utero, it “should act as a replacement for the missing EDA and trigger the process that leads to the normal development of a baby’s skin, teeth, hair, and sweat glands, leading to better formation of these structures.”

The protein is delivered into the amniotic fluid via a needle and syringe under ultrasound guidance. In a report on this treatment used in a pair of affected twins and a third XLHED-affected male published in 2018, the authors reported that the three babies were able to sweat normally after birth, “and XLHED-related illness had not developed by 14-22 months of age.”

The goal of the prospective, open-label, genotype match–controlled EDELIFE trial is to confirm the efficacy and safety results for ER004 in a larger group of boys, and to determine if it can lead to robust, and long-lasting improvement in XLHED-associated defects.

In the United States, the first pregnant woman to join the study received the treatment in February 2023 at Washington University in St. Louis. Other clinical sites are located in France, Germany, Italy, Spain, and the United Kingdom. Led by principal investigator Holm Schneider, MD, of the University Erlanger-Nurnberg (Germany), researchers are seeking to enroll mothers aged 18 years and older who are genetically confirmed carriers of the XLHED mutation and pregnant with a boy or considering pregnancy. The control group will include XLHED-affected males, 6 months to 60 years old, who are blood relatives of the pregnant woman participating in the study.

Clinicians treating affected families or potentially eligible subjects are encouraged to contact the trial investigators at this link.

Initiating oxycodone instead of codeine for postpartum analgesia was associated with an increased risk of persistent opioid use after vaginal, but not cesarean, delivery, new research suggests.

“In the last decade in Ontario, oxycodone surpassed codeine as the most commonly prescribed opioid postpartum for pain control,” Jonathan Zipursky, MD, PhD, of Sunnybrook Health Sciences Centre, ICES, Toronto, and the University of Toronto, said in an interview. “This likely had to do with concerns with codeine use during breastfeeding, many of which are unsubstantiated.

“We hypothesized that use of oxycodone would be associated with an increased risk of persistent postpartum opioid use,” he said. “However, we did not find this.”

Instead, other factors, such as the quantity of opioids initially prescribed, were probably more important risks, he said.

Sunnybrook Health Sciences Centre

Oxycodone okay

The investigators analyzed data from 70,607 people (median age, 32) who filled an opioid prescription within 7 days of discharge from the hospital between 2012 and 2020. Two-thirds (69.8%) received oxycodone and one-third received (30.2%) codeine.

The median gestational age at delivery was 39 weeks, and 80% of participants had a cesarean delivery. The median opioid prescription duration was 3 days. The median opioid content per prescription was 150 morphine milligram equivalents (MMEs) among those prescribed oxycodone and 135 MMEs for codeine.

The main outcome was persistent opioid use. This was defined as one or more additional prescriptions for an opioid within 90 days of the first postpartum prescription and one or more additional prescriptions in the 91-365 days after.

Oxycodone receipt was not associated with persistent opioid use, compared with codeine (relative risk, 1.04).

However, in a secondary analysis by mode of delivery, an association was seen between a prescription for oxycodone and persistent use after vaginal (RR, 1.63), but not after cesarean (RR, 0.85), delivery.

Dr. Zipursky noted that the quantity of opioids prescribed in the initial postpartum prescription “is likely a more important modifiable risk factor for new persistent opioid use, rather than the type of opioid prescribed.”

For example, a prescription containing more than 225 MMEs (equivalent to about 30 tablets of 5 mg oxycodone and to 50 tablets of 30 mg codeine) was associated with a roughly twofold increased risk of persistent use, compared with less than 112.5 MMEs after both vaginal (odds ratio, 2.51) and cesarean (OR, 1.78) delivery.

Furthermore, a prescription duration of more than 7 days was also associated with a roughly twofold increased risk of persistent use, compared with a duration of 1-3 days after both vaginal (OR, 2.43) and cesarean (OR, 1.52) delivery.

Most risk factors for persistent opioid use – a history of mental illness, substance use disorder, and more maternal comorbidities (aggregated diagnosis groups > 10) – were consistent across modes of delivery.

“Awareness of modifiable factors associated with new, persistent opioid use may help clinicians tailor opioid prescribing while ensuring adequate analgesia after delivery,” Dr. Zipursky suggested.
 

Less is more

In a comment, Elaine Duryea, MD, assistant professor in the department of obstetrics and gynecology at UT Southwestern Medical Center and medical director of the Maternal-Fetal Medicine Clinic at Parkland Health and Hospital System, both in Dallas, said, “It is likely exposure to any opioid, rather than a specific opioid, that can promote continued use – that is, past the medically indicated period.”

UT Southwestern Medical Center

Dr. Duryea was principal investigator of a study, published in the American Journal of Obstetrics and Gynecology, that showed a multimodal regimen that included scheduled nonsteroidal anti-inflammatory drugs and acetaminophen, with opioids used as needed, resulted in a decrease in opioid use while adequately controlling pain after cesarean delivery.

“It is important to understand how to appropriately tailor the amount of opioid given to patients at the time of hospital discharge after cesarean in order to treat pain effectively but not send patients home with more opioids than [are] really needed,” she said.

It is also important to “individualize prescribing practices and maximize the use of non-opioid medication to treat postpartum and postoperative pain. Opioids should be a last resort for breakthrough pain, not first-line therapy,” Dr. Duryea concluded.

The study was funded by a Canadian Institutes of Health Research project grant. Dr. Zipursky has received payments from private law firms for medicolegal opinions on the safety and effectiveness of analgesics, including opioids.

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

Initiating oxycodone instead of codeine for postpartum analgesia was associated with an increased risk of persistent opioid use after vaginal, but not cesarean, delivery, new research suggests.

“In the last decade in Ontario, oxycodone surpassed codeine as the most commonly prescribed opioid postpartum for pain control,” Jonathan Zipursky, MD, PhD, of Sunnybrook Health Sciences Centre, ICES, Toronto, and the University of Toronto, said in an interview. “This likely had to do with concerns with codeine use during breastfeeding, many of which are unsubstantiated.

“We hypothesized that use of oxycodone would be associated with an increased risk of persistent postpartum opioid use,” he said. “However, we did not find this.”

Instead, other factors, such as the quantity of opioids initially prescribed, were probably more important risks, he said.

Sunnybrook Health Sciences Centre

Oxycodone okay

The investigators analyzed data from 70,607 people (median age, 32) who filled an opioid prescription within 7 days of discharge from the hospital between 2012 and 2020. Two-thirds (69.8%) received oxycodone and one-third received (30.2%) codeine.

The median gestational age at delivery was 39 weeks, and 80% of participants had a cesarean delivery. The median opioid prescription duration was 3 days. The median opioid content per prescription was 150 morphine milligram equivalents (MMEs) among those prescribed oxycodone and 135 MMEs for codeine.

The main outcome was persistent opioid use. This was defined as one or more additional prescriptions for an opioid within 90 days of the first postpartum prescription and one or more additional prescriptions in the 91-365 days after.

Oxycodone receipt was not associated with persistent opioid use, compared with codeine (relative risk, 1.04).

However, in a secondary analysis by mode of delivery, an association was seen between a prescription for oxycodone and persistent use after vaginal (RR, 1.63), but not after cesarean (RR, 0.85), delivery.

Dr. Zipursky noted that the quantity of opioids prescribed in the initial postpartum prescription “is likely a more important modifiable risk factor for new persistent opioid use, rather than the type of opioid prescribed.”

For example, a prescription containing more than 225 MMEs (equivalent to about 30 tablets of 5 mg oxycodone and to 50 tablets of 30 mg codeine) was associated with a roughly twofold increased risk of persistent use, compared with less than 112.5 MMEs after both vaginal (odds ratio, 2.51) and cesarean (OR, 1.78) delivery.

Furthermore, a prescription duration of more than 7 days was also associated with a roughly twofold increased risk of persistent use, compared with a duration of 1-3 days after both vaginal (OR, 2.43) and cesarean (OR, 1.52) delivery.

Most risk factors for persistent opioid use – a history of mental illness, substance use disorder, and more maternal comorbidities (aggregated diagnosis groups > 10) – were consistent across modes of delivery.

“Awareness of modifiable factors associated with new, persistent opioid use may help clinicians tailor opioid prescribing while ensuring adequate analgesia after delivery,” Dr. Zipursky suggested.
 

Less is more

In a comment, Elaine Duryea, MD, assistant professor in the department of obstetrics and gynecology at UT Southwestern Medical Center and medical director of the Maternal-Fetal Medicine Clinic at Parkland Health and Hospital System, both in Dallas, said, “It is likely exposure to any opioid, rather than a specific opioid, that can promote continued use – that is, past the medically indicated period.”

UT Southwestern Medical Center

Dr. Duryea was principal investigator of a study, published in the American Journal of Obstetrics and Gynecology, that showed a multimodal regimen that included scheduled nonsteroidal anti-inflammatory drugs and acetaminophen, with opioids used as needed, resulted in a decrease in opioid use while adequately controlling pain after cesarean delivery.

“It is important to understand how to appropriately tailor the amount of opioid given to patients at the time of hospital discharge after cesarean in order to treat pain effectively but not send patients home with more opioids than [are] really needed,” she said.

It is also important to “individualize prescribing practices and maximize the use of non-opioid medication to treat postpartum and postoperative pain. Opioids should be a last resort for breakthrough pain, not first-line therapy,” Dr. Duryea concluded.

The study was funded by a Canadian Institutes of Health Research project grant. Dr. Zipursky has received payments from private law firms for medicolegal opinions on the safety and effectiveness of analgesics, including opioids.

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

Initiating oxycodone instead of codeine for postpartum analgesia was associated with an increased risk of persistent opioid use after vaginal, but not cesarean, delivery, new research suggests.

“In the last decade in Ontario, oxycodone surpassed codeine as the most commonly prescribed opioid postpartum for pain control,” Jonathan Zipursky, MD, PhD, of Sunnybrook Health Sciences Centre, ICES, Toronto, and the University of Toronto, said in an interview. “This likely had to do with concerns with codeine use during breastfeeding, many of which are unsubstantiated.

“We hypothesized that use of oxycodone would be associated with an increased risk of persistent postpartum opioid use,” he said. “However, we did not find this.”

Instead, other factors, such as the quantity of opioids initially prescribed, were probably more important risks, he said.

Sunnybrook Health Sciences Centre

Oxycodone okay

The investigators analyzed data from 70,607 people (median age, 32) who filled an opioid prescription within 7 days of discharge from the hospital between 2012 and 2020. Two-thirds (69.8%) received oxycodone and one-third received (30.2%) codeine.

The median gestational age at delivery was 39 weeks, and 80% of participants had a cesarean delivery. The median opioid prescription duration was 3 days. The median opioid content per prescription was 150 morphine milligram equivalents (MMEs) among those prescribed oxycodone and 135 MMEs for codeine.

The main outcome was persistent opioid use. This was defined as one or more additional prescriptions for an opioid within 90 days of the first postpartum prescription and one or more additional prescriptions in the 91-365 days after.

Oxycodone receipt was not associated with persistent opioid use, compared with codeine (relative risk, 1.04).

However, in a secondary analysis by mode of delivery, an association was seen between a prescription for oxycodone and persistent use after vaginal (RR, 1.63), but not after cesarean (RR, 0.85), delivery.

Dr. Zipursky noted that the quantity of opioids prescribed in the initial postpartum prescription “is likely a more important modifiable risk factor for new persistent opioid use, rather than the type of opioid prescribed.”

For example, a prescription containing more than 225 MMEs (equivalent to about 30 tablets of 5 mg oxycodone and to 50 tablets of 30 mg codeine) was associated with a roughly twofold increased risk of persistent use, compared with less than 112.5 MMEs after both vaginal (odds ratio, 2.51) and cesarean (OR, 1.78) delivery.

Furthermore, a prescription duration of more than 7 days was also associated with a roughly twofold increased risk of persistent use, compared with a duration of 1-3 days after both vaginal (OR, 2.43) and cesarean (OR, 1.52) delivery.

Most risk factors for persistent opioid use – a history of mental illness, substance use disorder, and more maternal comorbidities (aggregated diagnosis groups > 10) – were consistent across modes of delivery.

“Awareness of modifiable factors associated with new, persistent opioid use may help clinicians tailor opioid prescribing while ensuring adequate analgesia after delivery,” Dr. Zipursky suggested.
 

Less is more

In a comment, Elaine Duryea, MD, assistant professor in the department of obstetrics and gynecology at UT Southwestern Medical Center and medical director of the Maternal-Fetal Medicine Clinic at Parkland Health and Hospital System, both in Dallas, said, “It is likely exposure to any opioid, rather than a specific opioid, that can promote continued use – that is, past the medically indicated period.”

UT Southwestern Medical Center

Dr. Duryea was principal investigator of a study, published in the American Journal of Obstetrics and Gynecology, that showed a multimodal regimen that included scheduled nonsteroidal anti-inflammatory drugs and acetaminophen, with opioids used as needed, resulted in a decrease in opioid use while adequately controlling pain after cesarean delivery.

“It is important to understand how to appropriately tailor the amount of opioid given to patients at the time of hospital discharge after cesarean in order to treat pain effectively but not send patients home with more opioids than [are] really needed,” she said.

It is also important to “individualize prescribing practices and maximize the use of non-opioid medication to treat postpartum and postoperative pain. Opioids should be a last resort for breakthrough pain, not first-line therapy,” Dr. Duryea concluded.

The study was funded by a Canadian Institutes of Health Research project grant. Dr. Zipursky has received payments from private law firms for medicolegal opinions on the safety and effectiveness of analgesics, including opioids.

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

The Food and Drug Administration is considering approving a postpartum depression medication that can start working rapidly – in as little as 3 days. Promising results for the drug, zuranolone, were published recently in The American Journal of Psychiatry.

Approximately 17% of women are affected by postpartum depression (PPD) during pregnancy or after birth, study authors noted. The condition often results in reduced breastfeeding, poor maternal-infant bonding, and hindering behavioral, emotional and brain development of the baby. Severe PPD can lead to suicide of the mother, which accounts for 20% of all postpartum deaths, they wrote.

The study included 196 people who had given birth in the past year, and were between the ages of 18 and 45 years old. Participants had major depression that began in the 3rd trimester of pregnancy or during the first 4 weeks of the postpartum period. Among participants, 22% were Black and 38% were Hispanic.

Of those who took zuranolone, 57% had significantly improved depression symptoms after taking the drug for 14 days, and 27% were in remission at the conclusion of the 14-day treatment. The average time it took for symptoms to significantly decline was 9 days. Most people who saw improvements had them continue for the entire 45-day follow-up period. The most common side effects were drowsiness, dizziness, and sleepiness.

Currently, PPD treatment includes taking antidepressants, which can take up to 12 weeks to work. 

Researchers noted that the limitations of the study were that it only included women with severe PPD, and that women with a history of bipolar or psychotic disorders were excluded. Women in the study were not allowed to breastfeed, so the effect of zuranolone on lactation is unknown, they wrote.

A February news release from drugmaker Biogen indicated the FDA may decide whether to approve the medicine by Aug. 5.

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

The Food and Drug Administration is considering approving a postpartum depression medication that can start working rapidly – in as little as 3 days. Promising results for the drug, zuranolone, were published recently in The American Journal of Psychiatry.

Approximately 17% of women are affected by postpartum depression (PPD) during pregnancy or after birth, study authors noted. The condition often results in reduced breastfeeding, poor maternal-infant bonding, and hindering behavioral, emotional and brain development of the baby. Severe PPD can lead to suicide of the mother, which accounts for 20% of all postpartum deaths, they wrote.

The study included 196 people who had given birth in the past year, and were between the ages of 18 and 45 years old. Participants had major depression that began in the 3rd trimester of pregnancy or during the first 4 weeks of the postpartum period. Among participants, 22% were Black and 38% were Hispanic.

Of those who took zuranolone, 57% had significantly improved depression symptoms after taking the drug for 14 days, and 27% were in remission at the conclusion of the 14-day treatment. The average time it took for symptoms to significantly decline was 9 days. Most people who saw improvements had them continue for the entire 45-day follow-up period. The most common side effects were drowsiness, dizziness, and sleepiness.

Currently, PPD treatment includes taking antidepressants, which can take up to 12 weeks to work. 

Researchers noted that the limitations of the study were that it only included women with severe PPD, and that women with a history of bipolar or psychotic disorders were excluded. Women in the study were not allowed to breastfeed, so the effect of zuranolone on lactation is unknown, they wrote.

A February news release from drugmaker Biogen indicated the FDA may decide whether to approve the medicine by Aug. 5.

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

The Food and Drug Administration is considering approving a postpartum depression medication that can start working rapidly – in as little as 3 days. Promising results for the drug, zuranolone, were published recently in The American Journal of Psychiatry.

Approximately 17% of women are affected by postpartum depression (PPD) during pregnancy or after birth, study authors noted. The condition often results in reduced breastfeeding, poor maternal-infant bonding, and hindering behavioral, emotional and brain development of the baby. Severe PPD can lead to suicide of the mother, which accounts for 20% of all postpartum deaths, they wrote.

The study included 196 people who had given birth in the past year, and were between the ages of 18 and 45 years old. Participants had major depression that began in the 3rd trimester of pregnancy or during the first 4 weeks of the postpartum period. Among participants, 22% were Black and 38% were Hispanic.

Of those who took zuranolone, 57% had significantly improved depression symptoms after taking the drug for 14 days, and 27% were in remission at the conclusion of the 14-day treatment. The average time it took for symptoms to significantly decline was 9 days. Most people who saw improvements had them continue for the entire 45-day follow-up period. The most common side effects were drowsiness, dizziness, and sleepiness.

Currently, PPD treatment includes taking antidepressants, which can take up to 12 weeks to work. 

Researchers noted that the limitations of the study were that it only included women with severe PPD, and that women with a history of bipolar or psychotic disorders were excluded. Women in the study were not allowed to breastfeed, so the effect of zuranolone on lactation is unknown, they wrote.

A February news release from drugmaker Biogen indicated the FDA may decide whether to approve the medicine by Aug. 5.

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

A woman who was born without a uterus has given birth to a boy in Alabama.

It’s the first time that a baby has been born to a woman with a transplanted uterus outside of a clinical trial. Officials from University of Alabama–Birmingham Hospital, where the 2-year process took place, said in a statement on July 24 that the birth sets its uterus transplant program on track to perhaps become covered under insurance plans.

The process of uterus transplant, in vitro fertilization, and pregnancy involves 50 medical providers and is open to women who have uterine factor infertility (UFI). The condition may affect up to 5% of reproductive-age women worldwide. Women with UFI cannot carry a pregnancy to term because they were either born without a uterus, had it removed via hysterectomy, or have a uterus that does not function properly.

The woman, whom the hospital identified as Mallory, moved with her family to the Birmingham area to enter the transplant program, which is one of four programs operating in the United States. Mallory learned when she was 17 years old that she was born without a uterus because of Mayer-Rokitansky-Küster-Hauser syndrome. Her first child, a daughter, was born after her sister carried the pregnancy as a surrogate.

Mallory received her uterus from a deceased donor. Her son was born in May.

“As with other types of organ transplants, the woman must take immunosuppressive medications to prevent the body from rejecting the transplanted uterus,” the transplant program’s website states. “After the baby is born and if the woman does not want more children, the transplanted uterus is removed with a hysterectomy procedure, and the woman no longer needs to take antirejection medications.”

“There are all different ways to grow your family if you have uterine factor infertility, but this [uterus transplantation] is what I feel like I knew that I was supposed to do,” Mallory said in a statement. “I mean, just hearing the cry at first was just, you know, mind blowing.”

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

A woman who was born without a uterus has given birth to a boy in Alabama.

It’s the first time that a baby has been born to a woman with a transplanted uterus outside of a clinical trial. Officials from University of Alabama–Birmingham Hospital, where the 2-year process took place, said in a statement on July 24 that the birth sets its uterus transplant program on track to perhaps become covered under insurance plans.

The process of uterus transplant, in vitro fertilization, and pregnancy involves 50 medical providers and is open to women who have uterine factor infertility (UFI). The condition may affect up to 5% of reproductive-age women worldwide. Women with UFI cannot carry a pregnancy to term because they were either born without a uterus, had it removed via hysterectomy, or have a uterus that does not function properly.

The woman, whom the hospital identified as Mallory, moved with her family to the Birmingham area to enter the transplant program, which is one of four programs operating in the United States. Mallory learned when she was 17 years old that she was born without a uterus because of Mayer-Rokitansky-Küster-Hauser syndrome. Her first child, a daughter, was born after her sister carried the pregnancy as a surrogate.

Mallory received her uterus from a deceased donor. Her son was born in May.

“As with other types of organ transplants, the woman must take immunosuppressive medications to prevent the body from rejecting the transplanted uterus,” the transplant program’s website states. “After the baby is born and if the woman does not want more children, the transplanted uterus is removed with a hysterectomy procedure, and the woman no longer needs to take antirejection medications.”

“There are all different ways to grow your family if you have uterine factor infertility, but this [uterus transplantation] is what I feel like I knew that I was supposed to do,” Mallory said in a statement. “I mean, just hearing the cry at first was just, you know, mind blowing.”

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

A woman who was born without a uterus has given birth to a boy in Alabama.

It’s the first time that a baby has been born to a woman with a transplanted uterus outside of a clinical trial. Officials from University of Alabama–Birmingham Hospital, where the 2-year process took place, said in a statement on July 24 that the birth sets its uterus transplant program on track to perhaps become covered under insurance plans.

The process of uterus transplant, in vitro fertilization, and pregnancy involves 50 medical providers and is open to women who have uterine factor infertility (UFI). The condition may affect up to 5% of reproductive-age women worldwide. Women with UFI cannot carry a pregnancy to term because they were either born without a uterus, had it removed via hysterectomy, or have a uterus that does not function properly.

The woman, whom the hospital identified as Mallory, moved with her family to the Birmingham area to enter the transplant program, which is one of four programs operating in the United States. Mallory learned when she was 17 years old that she was born without a uterus because of Mayer-Rokitansky-Küster-Hauser syndrome. Her first child, a daughter, was born after her sister carried the pregnancy as a surrogate.

Mallory received her uterus from a deceased donor. Her son was born in May.

“As with other types of organ transplants, the woman must take immunosuppressive medications to prevent the body from rejecting the transplanted uterus,” the transplant program’s website states. “After the baby is born and if the woman does not want more children, the transplanted uterus is removed with a hysterectomy procedure, and the woman no longer needs to take antirejection medications.”

“There are all different ways to grow your family if you have uterine factor infertility, but this [uterus transplantation] is what I feel like I knew that I was supposed to do,” Mallory said in a statement. “I mean, just hearing the cry at first was just, you know, mind blowing.”

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

TOPLINE:

Chronic pancreatitis raises the risk for pregnancy complications, including gestational diabetes, gestational hypertensive complications, and preterm labor, according to a large study.

METHODOLOGY:

• A retrospective analysis of hospital discharge records from the National Inpatient Sample database between 2009 and 2019 was conducted.
• The sample included 3,094 pregnancies with chronic pancreatitis and roughly 40.8 million pregnancies without this condition.
• The study focused on primary maternal outcomes and primary perinatal outcomes in pregnancies affected by chronic pancreatitis after accounting for relevant covariates.

TAKEAWAY:

• Chronic pancreatitis pregnancies had elevated rates of gestational diabetes (adjusted odds ratio, 1.63), gestational hypertensive complications (aOR, 2.48), preterm labor (aOR, 3.10), and small size for gestational age (aOR, 2.40).
• Women with chronic pancreatitis and a history of renal failure were more prone to gestational hypertensive complications (aOR, 20.09).
• Women with alcohol-induced chronic pancreatitis had a 17-fold higher risk for fetal death (aOR, 17.15).
• Pregnancies with chronic pancreatitis were associated with longer hospital stays and higher hospital costs.

IN PRACTICE:

“Our study provides novel insights into the impact of chronic pancreatitis on maternal and fetal health. The implications of our findings are critical for health care professionals, particularly those involved in preconception counseling. Pregnant women with chronic pancreatitis should be under the care of a multidisciplinary team of health care providers,” the authors advise.

SOURCE:

The study was led by Chengu Niu, MD, with Rochester General Hospital, Rochester, N.Y. It was published online July 18 in Digestive and Liver Disease. The study had no specific funding.

LIMITATIONS:

The authors note potential inaccuracies because of coding in the National Inpatient Sample database, a lack of detailed information regarding medication use, and a lack of follow-up clinical information. The findings are specific to the United States and may not be applicable to other countries.

DISCLOSURES:

The authors have no relevant disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

Chronic pancreatitis raises the risk for pregnancy complications, including gestational diabetes, gestational hypertensive complications, and preterm labor, according to a large study.

METHODOLOGY:

• A retrospective analysis of hospital discharge records from the National Inpatient Sample database between 2009 and 2019 was conducted.
• The sample included 3,094 pregnancies with chronic pancreatitis and roughly 40.8 million pregnancies without this condition.
• The study focused on primary maternal outcomes and primary perinatal outcomes in pregnancies affected by chronic pancreatitis after accounting for relevant covariates.

TAKEAWAY:

• Chronic pancreatitis pregnancies had elevated rates of gestational diabetes (adjusted odds ratio, 1.63), gestational hypertensive complications (aOR, 2.48), preterm labor (aOR, 3.10), and small size for gestational age (aOR, 2.40).
• Women with chronic pancreatitis and a history of renal failure were more prone to gestational hypertensive complications (aOR, 20.09).
• Women with alcohol-induced chronic pancreatitis had a 17-fold higher risk for fetal death (aOR, 17.15).
• Pregnancies with chronic pancreatitis were associated with longer hospital stays and higher hospital costs.

IN PRACTICE:

“Our study provides novel insights into the impact of chronic pancreatitis on maternal and fetal health. The implications of our findings are critical for health care professionals, particularly those involved in preconception counseling. Pregnant women with chronic pancreatitis should be under the care of a multidisciplinary team of health care providers,” the authors advise.

SOURCE:

The study was led by Chengu Niu, MD, with Rochester General Hospital, Rochester, N.Y. It was published online July 18 in Digestive and Liver Disease. The study had no specific funding.

LIMITATIONS:

The authors note potential inaccuracies because of coding in the National Inpatient Sample database, a lack of detailed information regarding medication use, and a lack of follow-up clinical information. The findings are specific to the United States and may not be applicable to other countries.

DISCLOSURES:

The authors have no relevant disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

Chronic pancreatitis raises the risk for pregnancy complications, including gestational diabetes, gestational hypertensive complications, and preterm labor, according to a large study.

METHODOLOGY:

• A retrospective analysis of hospital discharge records from the National Inpatient Sample database between 2009 and 2019 was conducted.
• The sample included 3,094 pregnancies with chronic pancreatitis and roughly 40.8 million pregnancies without this condition.
• The study focused on primary maternal outcomes and primary perinatal outcomes in pregnancies affected by chronic pancreatitis after accounting for relevant covariates.

TAKEAWAY:

• Chronic pancreatitis pregnancies had elevated rates of gestational diabetes (adjusted odds ratio, 1.63), gestational hypertensive complications (aOR, 2.48), preterm labor (aOR, 3.10), and small size for gestational age (aOR, 2.40).
• Women with chronic pancreatitis and a history of renal failure were more prone to gestational hypertensive complications (aOR, 20.09).
• Women with alcohol-induced chronic pancreatitis had a 17-fold higher risk for fetal death (aOR, 17.15).
• Pregnancies with chronic pancreatitis were associated with longer hospital stays and higher hospital costs.

IN PRACTICE:

“Our study provides novel insights into the impact of chronic pancreatitis on maternal and fetal health. The implications of our findings are critical for health care professionals, particularly those involved in preconception counseling. Pregnant women with chronic pancreatitis should be under the care of a multidisciplinary team of health care providers,” the authors advise.

SOURCE:

The study was led by Chengu Niu, MD, with Rochester General Hospital, Rochester, N.Y. It was published online July 18 in Digestive and Liver Disease. The study had no specific funding.

LIMITATIONS:

The authors note potential inaccuracies because of coding in the National Inpatient Sample database, a lack of detailed information regarding medication use, and a lack of follow-up clinical information. The findings are specific to the United States and may not be applicable to other countries.

DISCLOSURES:

The authors have no relevant disclosures.

A version of this article appeared on Medscape.com.

Higher rates of cervical cancer screening are associated with an increased risk of preterm delivery (PTD) in young nulliparous women aged 18-24 years, a large population-based study found.

For each additional recommended screening before childbirth, there was a direct increase in absolute PTD risk of 0.073 (95% confidence interval, 0.026-0.120), according to a study led by Rebecca A. Bromley-Dulfano, MS, an MD candidate at Stanford (Calif.) University and a PhD candidate in health policy at Harvard University, Cambridge, Mass.

courtesy Ms. Bromley-Dulfano

There was no significant change in very preterm delivery (VPTD) risk, but mothers with hypertension or diabetes were at higher PTD risk.

Women in this younger age group are more prone to PTD. According to the study’s estimate, an additional 73 PTDs per 100,000 women could be expected for every 1 additional recommended screening before childbirth. For the year 2018, that translated to an estimated 1,348 PTDs that could have been averted, with reduced screening requirements (3% relative reduction).

“If you screen someone for cervical cancer and find a cervical lesion, the possible next steps can include a biopsy and an excisional procedure to remove the lesion,” Ms. Bromley-Dulfano explained, “and these procedures which remove a small (mostly diseased) part of the cervix have been shown to slightly increase the risk of PTD. Particularly in young individuals with a cervix who are known to have high rates of lesion regression and who have more potential childbearing years ahead of them, it is important to weigh the oncological benefits with the adverse birth outcome risks.” 

Young women are more likely to have false-positive results on Papanicolaou tests and lesion regression within 2 years but may undergo unnecessary treatment, the authors noted.

Cervical excision procedures have previously been associated in clinical trials with an increase in PTB risk.

In their 2017 decision model in a fictive cohort, for example, Kamphuis and colleagues found the most intensive screening program was associated with an increase in maternal life years of 9%, a decrease in cervical cancer incidence of 67%, and a decrease in cervical cancer deaths of 75%. But those gains came at the cost of 250% more preterm births, compared with the least intensive program.

“These results can be used in future simulation models integrating oncological trade-offs to help ascertain optimal screening strategies,” the researchers wrote.

While the optimal screening strategy must trade off the oncologic benefits of cancer detection against the neonatal harms of overtreatment, the ideal age of cervical cancer screening onset and frequency remain uncertain, the authors noted. Recent American Cancer Society guidelines recommending less frequent screening for some diverge from those of other societies.

“The first and foremost priority is for gynecologists to continue to have individualized conversations with patients about all of the benefits and risks of procedures that patients undergo and to understand the benefits and risks influencing screening guidelines,” Ms. Bromley-Dulfano said.
 

Cross-sectional study

The study used data from the Centers for Disease Control and Prevention’s National Center for Health Statistics to analyze associations between cervical cancer screening guidelines and birth outcomes women who had a singleton nulliparous birth from 19916 to 2018. Gestational age and maternal characteristics were drawn from birth certificates.

The mean age of the 11,333,151 multiracial cohort of women was 20.9 years, and 6.8% had hypertension or diabetes. The mean number of guideline-recommended screenings by time of childbirth was 2.4. Overall, PTD and very PTD occurred in 1,140,490 individuals (10.1%) and 333,040 (2.9%) of births, respectively.

Those with hypertension or diabetes had a somewhat higher PTD risk: 0.26% (95% CI, 0.11-0.4) versus 0.06% (95% CI, 0.01-0.10; Wald test, P < .001).

courtesy Northwell Health

Offering an outsider’s perspective on the analysis, ob.gyn. Fidel A. Valea, MD, director of gynecologic oncology at the Northwell Health Cancer Institute in New Hyde Park, N.Y., urged caution in drawing conclusions from large population analyses such as this.

“This study had over 11 million data points. Often these large numbers will show statistical differences that are not clinically significant,” he said in an interview. He noted that while small studies have shown a possible impact of frequent Pap tests on cervical function, “this is not 100% proven. Research from Texas showed that screening made a difference only in cases of dysplasia.”

Dr. Valea also noted that screening guidelines have already changed over the lengthy time span of the study and do reflect the concerns of the study authors.

“We know that the HPV virus is cleared more readily by young women than older women and so we have made adjustments and test them less frequently and we test them less early.” He added that conservative options are recommended even in the case of dysplasia.

In defense of the Pap smear test, he added: “It has virtually wiped out cervical cancer in the U.S., bringing it from No. 1 to No. 13.” While broadening HPV vaccination programs may impact guidelines in the future, “vaccination is still in its infancy. We have to wait until women have lived long to enough to see an impact.”

As to why this age group is more vulnerable to PTD, Dr. Valea said, “It’s likely multifactorial, with lifestyle and other factors involved.” Although based on U.S. data, the authors said their results may be useful for other public health entities, particularly in countries where cervical cancer is considerably more prevalent.

This work received no specific funding. The authors and Dr. Valea disclosed no competing interests.

Higher rates of cervical cancer screening are associated with an increased risk of preterm delivery (PTD) in young nulliparous women aged 18-24 years, a large population-based study found.

For each additional recommended screening before childbirth, there was a direct increase in absolute PTD risk of 0.073 (95% confidence interval, 0.026-0.120), according to a study led by Rebecca A. Bromley-Dulfano, MS, an MD candidate at Stanford (Calif.) University and a PhD candidate in health policy at Harvard University, Cambridge, Mass.

courtesy Ms. Bromley-Dulfano

There was no significant change in very preterm delivery (VPTD) risk, but mothers with hypertension or diabetes were at higher PTD risk.

Women in this younger age group are more prone to PTD. According to the study’s estimate, an additional 73 PTDs per 100,000 women could be expected for every 1 additional recommended screening before childbirth. For the year 2018, that translated to an estimated 1,348 PTDs that could have been averted, with reduced screening requirements (3% relative reduction).

“If you screen someone for cervical cancer and find a cervical lesion, the possible next steps can include a biopsy and an excisional procedure to remove the lesion,” Ms. Bromley-Dulfano explained, “and these procedures which remove a small (mostly diseased) part of the cervix have been shown to slightly increase the risk of PTD. Particularly in young individuals with a cervix who are known to have high rates of lesion regression and who have more potential childbearing years ahead of them, it is important to weigh the oncological benefits with the adverse birth outcome risks.” 

Young women are more likely to have false-positive results on Papanicolaou tests and lesion regression within 2 years but may undergo unnecessary treatment, the authors noted.

Cervical excision procedures have previously been associated in clinical trials with an increase in PTB risk.

In their 2017 decision model in a fictive cohort, for example, Kamphuis and colleagues found the most intensive screening program was associated with an increase in maternal life years of 9%, a decrease in cervical cancer incidence of 67%, and a decrease in cervical cancer deaths of 75%. But those gains came at the cost of 250% more preterm births, compared with the least intensive program.

“These results can be used in future simulation models integrating oncological trade-offs to help ascertain optimal screening strategies,” the researchers wrote.

While the optimal screening strategy must trade off the oncologic benefits of cancer detection against the neonatal harms of overtreatment, the ideal age of cervical cancer screening onset and frequency remain uncertain, the authors noted. Recent American Cancer Society guidelines recommending less frequent screening for some diverge from those of other societies.

“The first and foremost priority is for gynecologists to continue to have individualized conversations with patients about all of the benefits and risks of procedures that patients undergo and to understand the benefits and risks influencing screening guidelines,” Ms. Bromley-Dulfano said.
 

Cross-sectional study

The study used data from the Centers for Disease Control and Prevention’s National Center for Health Statistics to analyze associations between cervical cancer screening guidelines and birth outcomes women who had a singleton nulliparous birth from 19916 to 2018. Gestational age and maternal characteristics were drawn from birth certificates.

The mean age of the 11,333,151 multiracial cohort of women was 20.9 years, and 6.8% had hypertension or diabetes. The mean number of guideline-recommended screenings by time of childbirth was 2.4. Overall, PTD and very PTD occurred in 1,140,490 individuals (10.1%) and 333,040 (2.9%) of births, respectively.

Those with hypertension or diabetes had a somewhat higher PTD risk: 0.26% (95% CI, 0.11-0.4) versus 0.06% (95% CI, 0.01-0.10; Wald test, P < .001).

courtesy Northwell Health

Offering an outsider’s perspective on the analysis, ob.gyn. Fidel A. Valea, MD, director of gynecologic oncology at the Northwell Health Cancer Institute in New Hyde Park, N.Y., urged caution in drawing conclusions from large population analyses such as this.

“This study had over 11 million data points. Often these large numbers will show statistical differences that are not clinically significant,” he said in an interview. He noted that while small studies have shown a possible impact of frequent Pap tests on cervical function, “this is not 100% proven. Research from Texas showed that screening made a difference only in cases of dysplasia.”

Dr. Valea also noted that screening guidelines have already changed over the lengthy time span of the study and do reflect the concerns of the study authors.

“We know that the HPV virus is cleared more readily by young women than older women and so we have made adjustments and test them less frequently and we test them less early.” He added that conservative options are recommended even in the case of dysplasia.

In defense of the Pap smear test, he added: “It has virtually wiped out cervical cancer in the U.S., bringing it from No. 1 to No. 13.” While broadening HPV vaccination programs may impact guidelines in the future, “vaccination is still in its infancy. We have to wait until women have lived long to enough to see an impact.”

As to why this age group is more vulnerable to PTD, Dr. Valea said, “It’s likely multifactorial, with lifestyle and other factors involved.” Although based on U.S. data, the authors said their results may be useful for other public health entities, particularly in countries where cervical cancer is considerably more prevalent.

This work received no specific funding. The authors and Dr. Valea disclosed no competing interests.

Higher rates of cervical cancer screening are associated with an increased risk of preterm delivery (PTD) in young nulliparous women aged 18-24 years, a large population-based study found.

For each additional recommended screening before childbirth, there was a direct increase in absolute PTD risk of 0.073 (95% confidence interval, 0.026-0.120), according to a study led by Rebecca A. Bromley-Dulfano, MS, an MD candidate at Stanford (Calif.) University and a PhD candidate in health policy at Harvard University, Cambridge, Mass.

courtesy Ms. Bromley-Dulfano

There was no significant change in very preterm delivery (VPTD) risk, but mothers with hypertension or diabetes were at higher PTD risk.

Women in this younger age group are more prone to PTD. According to the study’s estimate, an additional 73 PTDs per 100,000 women could be expected for every 1 additional recommended screening before childbirth. For the year 2018, that translated to an estimated 1,348 PTDs that could have been averted, with reduced screening requirements (3% relative reduction).

“If you screen someone for cervical cancer and find a cervical lesion, the possible next steps can include a biopsy and an excisional procedure to remove the lesion,” Ms. Bromley-Dulfano explained, “and these procedures which remove a small (mostly diseased) part of the cervix have been shown to slightly increase the risk of PTD. Particularly in young individuals with a cervix who are known to have high rates of lesion regression and who have more potential childbearing years ahead of them, it is important to weigh the oncological benefits with the adverse birth outcome risks.” 

Young women are more likely to have false-positive results on Papanicolaou tests and lesion regression within 2 years but may undergo unnecessary treatment, the authors noted.

Cervical excision procedures have previously been associated in clinical trials with an increase in PTB risk.

In their 2017 decision model in a fictive cohort, for example, Kamphuis and colleagues found the most intensive screening program was associated with an increase in maternal life years of 9%, a decrease in cervical cancer incidence of 67%, and a decrease in cervical cancer deaths of 75%. But those gains came at the cost of 250% more preterm births, compared with the least intensive program.

“These results can be used in future simulation models integrating oncological trade-offs to help ascertain optimal screening strategies,” the researchers wrote.

While the optimal screening strategy must trade off the oncologic benefits of cancer detection against the neonatal harms of overtreatment, the ideal age of cervical cancer screening onset and frequency remain uncertain, the authors noted. Recent American Cancer Society guidelines recommending less frequent screening for some diverge from those of other societies.

“The first and foremost priority is for gynecologists to continue to have individualized conversations with patients about all of the benefits and risks of procedures that patients undergo and to understand the benefits and risks influencing screening guidelines,” Ms. Bromley-Dulfano said.
 

Cross-sectional study

The study used data from the Centers for Disease Control and Prevention’s National Center for Health Statistics to analyze associations between cervical cancer screening guidelines and birth outcomes women who had a singleton nulliparous birth from 19916 to 2018. Gestational age and maternal characteristics were drawn from birth certificates.

The mean age of the 11,333,151 multiracial cohort of women was 20.9 years, and 6.8% had hypertension or diabetes. The mean number of guideline-recommended screenings by time of childbirth was 2.4. Overall, PTD and very PTD occurred in 1,140,490 individuals (10.1%) and 333,040 (2.9%) of births, respectively.

Those with hypertension or diabetes had a somewhat higher PTD risk: 0.26% (95% CI, 0.11-0.4) versus 0.06% (95% CI, 0.01-0.10; Wald test, P < .001).

courtesy Northwell Health

Offering an outsider’s perspective on the analysis, ob.gyn. Fidel A. Valea, MD, director of gynecologic oncology at the Northwell Health Cancer Institute in New Hyde Park, N.Y., urged caution in drawing conclusions from large population analyses such as this.

“This study had over 11 million data points. Often these large numbers will show statistical differences that are not clinically significant,” he said in an interview. He noted that while small studies have shown a possible impact of frequent Pap tests on cervical function, “this is not 100% proven. Research from Texas showed that screening made a difference only in cases of dysplasia.”

Dr. Valea also noted that screening guidelines have already changed over the lengthy time span of the study and do reflect the concerns of the study authors.

“We know that the HPV virus is cleared more readily by young women than older women and so we have made adjustments and test them less frequently and we test them less early.” He added that conservative options are recommended even in the case of dysplasia.

In defense of the Pap smear test, he added: “It has virtually wiped out cervical cancer in the U.S., bringing it from No. 1 to No. 13.” While broadening HPV vaccination programs may impact guidelines in the future, “vaccination is still in its infancy. We have to wait until women have lived long to enough to see an impact.”

As to why this age group is more vulnerable to PTD, Dr. Valea said, “It’s likely multifactorial, with lifestyle and other factors involved.” Although based on U.S. data, the authors said their results may be useful for other public health entities, particularly in countries where cervical cancer is considerably more prevalent.

This work received no specific funding. The authors and Dr. Valea disclosed no competing interests.

REPRODUCTIVE ROUNDS

Applications of office hysteroscopy for the infertility patient

J. Preston Parry, MD, MPH; Mark Trolice, MD, MBA

What role does diagnostic office hysteroscopy play in an infertility evaluation?

Performed properly, office hysteroscopy can transform your practice by accurately, gently, and safely assessing the uterine cavity as well as assessing tubal patency.

More specifically, hysteroscopy is the gold standard for assessing the uterine cavity. The sensitivity, specificity, and positive predictive and negative predictive values of hysterosalpingography (HSG) in evaluating uterine cavity abnormalities were 44.83%; 86.67%; 56.52%; and 80.25%, respectively. Given the poor sensitivity of HSG, a diagnosis of endometrial polyps and/or chronic endometritis is more likely to be missed.

Our crossover trial comparing HSG to office hysteroscopy for tubal patency showed that women were 110 times more likely to have the maximum level of pain with HSG than diagnostic hysteroscopy when using a 2.8-mm flexible hysteroscope. Further, infection rates and vasovagal events were far lower with hysteroscopy.

Finally, compared with HSG, we showed 98%-100% sensitivity and 84% specificity for tubal occlusion with hysteroscopy by air-infused saline. Conversely, HSG typically is associated with 76%-96% sensitivity and 67%-100% specificity. Additionally, we can often perform diagnostic hysteroscopies for approximately $35 per procedure for total fixed and disposable equipment costs.

https://www.mdedge.com/obgyn/reproductive-rounds

FEATURE

Is ChatGPT a friend or foe of medical publishing?

Lucy Hicks

Researchers may use artificial intelligence (AI) language models such as ChatGPT to write and revise scientific manuscripts, according to a new announcement from the International Committee of Medical Journal Editors. These tools should not be listed as authors, and researchers must denote how AI-assisted technologies were used, the committee said.

These new guidelines are the latest effort for medical journals to define policies for using these large-scale language models (LLMs) in scientific publication. While these AI-assisted tools can help with tasks such as writing, analyzing data, catching mistakes, and more, they are also prone to errors, noted Casey Greene, PhD, a professor of biomedical informatics at the University of Colorado at Denver, Aurora.

At the same time, experts argue that these AI tools could have a positive impact on the field by limiting some of the linguistic disparities in scientific publishing as well as alleviating the burden of some monotonous or mechanical tasks that come along with manuscript writing.

What experts can agree on, though, is that the use of AI tools is here to stay. “This is going to become a common tool,” Dr. Greene said.

A change in medical publishing

OpenAI released ChatGPT in November 2022. In its own words, ChatGPT is “a deep learning model that has been trained on a massive amount of text data to understand and generate humanlike text.” Enter a question or a prompt, and it will respond. For example, when asked how the AI tool can be used in scientific publishing, ChatGPT responded:

“ChatGPT can aid scientific publishing by generating ideas, clarifying concepts, conducting preliminary literature reviews, providing proofreading and editing suggestions, and assisting with outlining and organizing scientific papers. However, it should be used as a supportive tool alongside domain expertise and validation from trusted scientific sources.”

Just a few months after ChatGPT became available, researchers began using this tool in their own work. One individual, Som Biswas, MD, a radiologist at the University of Tennessee Health Science Center in Memphis, reportedly used ChatGPT to author 16 scientific articles in just 4 months, according to the Daily Beast. Five of these articles have been published in four different journals. Dr. Biswas declined to be interviewed for this article.

There were also reports of papers with ChatGPT as one of the listed authors, which sparked backlash. In response, JAMA, Nature, and Science all published editorials in January outlining their policies for using ChatGPT and other large language models in the scientific authoring process. Editors from the journals of the American College of Cardiology and the American College of Rheumatology also updated their policies to reflect the influence of AI authoring tools.

The consensus is that AI has no place on the author byline.

https://www.mdedge.com/obgyn/article/263471/business-medicine/chatgpt-friend-or-foe-medical-publishing

Continue to: FROM THE JOURNALS...

FROM THE JOURNALS

Review supports continued mask-wearing in health care visits

Jay Croft

A new study urges people to continue wearing protective masks in medical settings, even though the U.S. public health emergency declaration around COVID-19 has expired.

Masks continue to lower the risk of catching the virus during medical visits, according to the study, published in Annals of Internal Medicine. And there was not much difference between wearing surgical masks and N95 respirators in health care settings.

The researchers reviewed 3 randomized trials and 21 observational studies to compare the effectiveness of those and cloth masks in reducing COVID-19 transmission.

“Masking in interactions between patients and health care personnel should continue to receive serious consideration as a patient safety measure,” Tara N. Palmore, MD, of George Washington University, Washington, and David K. Henderson, MD, of the National Institutes of Health, Bethesda, Md., wrote in an opinion article accompanying the study.

“In our enthusiasm to return to the appearance and feeling of normalcy, and as institutions decide which mitigation strategies to discontinue, we strongly advocate not discarding this important lesson learned for the sake of our patients’ safety,” Dr. Palmore and Dr. Henderson wrote.

Surgical masks limit the spread of aerosols and droplets from people who have the flu, coronaviruses or other respiratory viruses, CNN reported. And while masks are not 100% effective, they substantially lower the amount of virus put into the air via coughing and talking.

https://www.mdedge.com/obgyn/covid-19-updates

CONFERENCE COVERAGE

A ‘one-stop shop’: New guidance on hormones and aging

Miriam E. Tucker

A new statement from the Endocrine Society on hormones and aging highlights the differences between normal aging and disease, and when treatment is and isn’t appropriate.

The idea of the statement “is to be complete, but also to clarify some misunderstandings. ...We tried to be very clear in the language about what we know, where we can go, where we shouldn’t go, and what we still need to learn,” statement coauthor Cynthia A. Stuenkel, MD, of the University of California, San Diego, said in an interview.

The document is divided into nine parts or axes: growth hormone, adrenal, ovarian, testicular, thyroid, osteoporosis, vitamin D deficiency, type 2 diabetes, and water metabolism. Each section covers natural history and observational data in older individuals, available therapies, clinical trial data on efficacy and safety in older individuals, bulleted “key points,” and research gaps.

“Hormones and Aging: An Endocrine Society Scientific Statement” was presented at the annual meeting of the Endocrine Society and published online in the Journal of Clinical Endocrinology & Metabolism.

During a press briefing, writing group chair Anne R. Cappola, MD, of the University of Pennsylvania, Philadelphia, said the goal is to “provide a really concise summary across each of these areas. ... There are multiple hormonal changes that occur with age, so we really couldn’t limit ourselves to just one gland or the few that we commonly think about. We wanted to cover all the axes.”

The statement tackles several controversial areas, including hormone therapy for menopausal symptoms in women and hypogonadal symptoms in men and diabetes treatment goals in older adults.

“Hormones have these almost mythical qualities to some people. ... ‘If I just had my hormones back the way they were, it would all work out.’ What we want to do is make sure that patients are being treated appropriately and that their symptoms are being heard and managed and ascribed to the appropriate problems and not necessarily to hormonal problems when they are not. ... Part of what we need to do is [provide] the evidence that we have, which includes evidence of when not to prescribe as well as [when] to prescribe,” Dr. Cappola said.

https://www.mdedge.com/obgyn/conference-coverage ●

REPRODUCTIVE ROUNDS

Applications of office hysteroscopy for the infertility patient

J. Preston Parry, MD, MPH; Mark Trolice, MD, MBA

What role does diagnostic office hysteroscopy play in an infertility evaluation?

Performed properly, office hysteroscopy can transform your practice by accurately, gently, and safely assessing the uterine cavity as well as assessing tubal patency.

More specifically, hysteroscopy is the gold standard for assessing the uterine cavity. The sensitivity, specificity, and positive predictive and negative predictive values of hysterosalpingography (HSG) in evaluating uterine cavity abnormalities were 44.83%; 86.67%; 56.52%; and 80.25%, respectively. Given the poor sensitivity of HSG, a diagnosis of endometrial polyps and/or chronic endometritis is more likely to be missed.

Our crossover trial comparing HSG to office hysteroscopy for tubal patency showed that women were 110 times more likely to have the maximum level of pain with HSG than diagnostic hysteroscopy when using a 2.8-mm flexible hysteroscope. Further, infection rates and vasovagal events were far lower with hysteroscopy.

Finally, compared with HSG, we showed 98%-100% sensitivity and 84% specificity for tubal occlusion with hysteroscopy by air-infused saline. Conversely, HSG typically is associated with 76%-96% sensitivity and 67%-100% specificity. Additionally, we can often perform diagnostic hysteroscopies for approximately $35 per procedure for total fixed and disposable equipment costs.

https://www.mdedge.com/obgyn/reproductive-rounds

FEATURE

Is ChatGPT a friend or foe of medical publishing?

Lucy Hicks

Researchers may use artificial intelligence (AI) language models such as ChatGPT to write and revise scientific manuscripts, according to a new announcement from the International Committee of Medical Journal Editors. These tools should not be listed as authors, and researchers must denote how AI-assisted technologies were used, the committee said.

These new guidelines are the latest effort for medical journals to define policies for using these large-scale language models (LLMs) in scientific publication. While these AI-assisted tools can help with tasks such as writing, analyzing data, catching mistakes, and more, they are also prone to errors, noted Casey Greene, PhD, a professor of biomedical informatics at the University of Colorado at Denver, Aurora.

At the same time, experts argue that these AI tools could have a positive impact on the field by limiting some of the linguistic disparities in scientific publishing as well as alleviating the burden of some monotonous or mechanical tasks that come along with manuscript writing.

What experts can agree on, though, is that the use of AI tools is here to stay. “This is going to become a common tool,” Dr. Greene said.

A change in medical publishing

OpenAI released ChatGPT in November 2022. In its own words, ChatGPT is “a deep learning model that has been trained on a massive amount of text data to understand and generate humanlike text.” Enter a question or a prompt, and it will respond. For example, when asked how the AI tool can be used in scientific publishing, ChatGPT responded:

“ChatGPT can aid scientific publishing by generating ideas, clarifying concepts, conducting preliminary literature reviews, providing proofreading and editing suggestions, and assisting with outlining and organizing scientific papers. However, it should be used as a supportive tool alongside domain expertise and validation from trusted scientific sources.”

Just a few months after ChatGPT became available, researchers began using this tool in their own work. One individual, Som Biswas, MD, a radiologist at the University of Tennessee Health Science Center in Memphis, reportedly used ChatGPT to author 16 scientific articles in just 4 months, according to the Daily Beast. Five of these articles have been published in four different journals. Dr. Biswas declined to be interviewed for this article.

There were also reports of papers with ChatGPT as one of the listed authors, which sparked backlash. In response, JAMA, Nature, and Science all published editorials in January outlining their policies for using ChatGPT and other large language models in the scientific authoring process. Editors from the journals of the American College of Cardiology and the American College of Rheumatology also updated their policies to reflect the influence of AI authoring tools.

The consensus is that AI has no place on the author byline.

https://www.mdedge.com/obgyn/article/263471/business-medicine/chatgpt-friend-or-foe-medical-publishing

Continue to: FROM THE JOURNALS...

FROM THE JOURNALS

Review supports continued mask-wearing in health care visits

Jay Croft

A new study urges people to continue wearing protective masks in medical settings, even though the U.S. public health emergency declaration around COVID-19 has expired.

Masks continue to lower the risk of catching the virus during medical visits, according to the study, published in Annals of Internal Medicine. And there was not much difference between wearing surgical masks and N95 respirators in health care settings.

The researchers reviewed 3 randomized trials and 21 observational studies to compare the effectiveness of those and cloth masks in reducing COVID-19 transmission.

“Masking in interactions between patients and health care personnel should continue to receive serious consideration as a patient safety measure,” Tara N. Palmore, MD, of George Washington University, Washington, and David K. Henderson, MD, of the National Institutes of Health, Bethesda, Md., wrote in an opinion article accompanying the study.

“In our enthusiasm to return to the appearance and feeling of normalcy, and as institutions decide which mitigation strategies to discontinue, we strongly advocate not discarding this important lesson learned for the sake of our patients’ safety,” Dr. Palmore and Dr. Henderson wrote.

Surgical masks limit the spread of aerosols and droplets from people who have the flu, coronaviruses or other respiratory viruses, CNN reported. And while masks are not 100% effective, they substantially lower the amount of virus put into the air via coughing and talking.

https://www.mdedge.com/obgyn/covid-19-updates

CONFERENCE COVERAGE

A ‘one-stop shop’: New guidance on hormones and aging

Miriam E. Tucker

A new statement from the Endocrine Society on hormones and aging highlights the differences between normal aging and disease, and when treatment is and isn’t appropriate.

The idea of the statement “is to be complete, but also to clarify some misunderstandings. ...We tried to be very clear in the language about what we know, where we can go, where we shouldn’t go, and what we still need to learn,” statement coauthor Cynthia A. Stuenkel, MD, of the University of California, San Diego, said in an interview.

The document is divided into nine parts or axes: growth hormone, adrenal, ovarian, testicular, thyroid, osteoporosis, vitamin D deficiency, type 2 diabetes, and water metabolism. Each section covers natural history and observational data in older individuals, available therapies, clinical trial data on efficacy and safety in older individuals, bulleted “key points,” and research gaps.

“Hormones and Aging: An Endocrine Society Scientific Statement” was presented at the annual meeting of the Endocrine Society and published online in the Journal of Clinical Endocrinology & Metabolism.

During a press briefing, writing group chair Anne R. Cappola, MD, of the University of Pennsylvania, Philadelphia, said the goal is to “provide a really concise summary across each of these areas. ... There are multiple hormonal changes that occur with age, so we really couldn’t limit ourselves to just one gland or the few that we commonly think about. We wanted to cover all the axes.”

The statement tackles several controversial areas, including hormone therapy for menopausal symptoms in women and hypogonadal symptoms in men and diabetes treatment goals in older adults.

“Hormones have these almost mythical qualities to some people. ... ‘If I just had my hormones back the way they were, it would all work out.’ What we want to do is make sure that patients are being treated appropriately and that their symptoms are being heard and managed and ascribed to the appropriate problems and not necessarily to hormonal problems when they are not. ... Part of what we need to do is [provide] the evidence that we have, which includes evidence of when not to prescribe as well as [when] to prescribe,” Dr. Cappola said.

https://www.mdedge.com/obgyn/conference-coverage ●

REPRODUCTIVE ROUNDS

Applications of office hysteroscopy for the infertility patient

J. Preston Parry, MD, MPH; Mark Trolice, MD, MBA

What role does diagnostic office hysteroscopy play in an infertility evaluation?

Performed properly, office hysteroscopy can transform your practice by accurately, gently, and safely assessing the uterine cavity as well as assessing tubal patency.

More specifically, hysteroscopy is the gold standard for assessing the uterine cavity. The sensitivity, specificity, and positive predictive and negative predictive values of hysterosalpingography (HSG) in evaluating uterine cavity abnormalities were 44.83%; 86.67%; 56.52%; and 80.25%, respectively. Given the poor sensitivity of HSG, a diagnosis of endometrial polyps and/or chronic endometritis is more likely to be missed.

Our crossover trial comparing HSG to office hysteroscopy for tubal patency showed that women were 110 times more likely to have the maximum level of pain with HSG than diagnostic hysteroscopy when using a 2.8-mm flexible hysteroscope. Further, infection rates and vasovagal events were far lower with hysteroscopy.

Finally, compared with HSG, we showed 98%-100% sensitivity and 84% specificity for tubal occlusion with hysteroscopy by air-infused saline. Conversely, HSG typically is associated with 76%-96% sensitivity and 67%-100% specificity. Additionally, we can often perform diagnostic hysteroscopies for approximately $35 per procedure for total fixed and disposable equipment costs.

https://www.mdedge.com/obgyn/reproductive-rounds

FEATURE

Is ChatGPT a friend or foe of medical publishing?

Lucy Hicks

Researchers may use artificial intelligence (AI) language models such as ChatGPT to write and revise scientific manuscripts, according to a new announcement from the International Committee of Medical Journal Editors. These tools should not be listed as authors, and researchers must denote how AI-assisted technologies were used, the committee said.

These new guidelines are the latest effort for medical journals to define policies for using these large-scale language models (LLMs) in scientific publication. While these AI-assisted tools can help with tasks such as writing, analyzing data, catching mistakes, and more, they are also prone to errors, noted Casey Greene, PhD, a professor of biomedical informatics at the University of Colorado at Denver, Aurora.

At the same time, experts argue that these AI tools could have a positive impact on the field by limiting some of the linguistic disparities in scientific publishing as well as alleviating the burden of some monotonous or mechanical tasks that come along with manuscript writing.

What experts can agree on, though, is that the use of AI tools is here to stay. “This is going to become a common tool,” Dr. Greene said.

A change in medical publishing

OpenAI released ChatGPT in November 2022. In its own words, ChatGPT is “a deep learning model that has been trained on a massive amount of text data to understand and generate humanlike text.” Enter a question or a prompt, and it will respond. For example, when asked how the AI tool can be used in scientific publishing, ChatGPT responded:

“ChatGPT can aid scientific publishing by generating ideas, clarifying concepts, conducting preliminary literature reviews, providing proofreading and editing suggestions, and assisting with outlining and organizing scientific papers. However, it should be used as a supportive tool alongside domain expertise and validation from trusted scientific sources.”

Just a few months after ChatGPT became available, researchers began using this tool in their own work. One individual, Som Biswas, MD, a radiologist at the University of Tennessee Health Science Center in Memphis, reportedly used ChatGPT to author 16 scientific articles in just 4 months, according to the Daily Beast. Five of these articles have been published in four different journals. Dr. Biswas declined to be interviewed for this article.

There were also reports of papers with ChatGPT as one of the listed authors, which sparked backlash. In response, JAMA, Nature, and Science all published editorials in January outlining their policies for using ChatGPT and other large language models in the scientific authoring process. Editors from the journals of the American College of Cardiology and the American College of Rheumatology also updated their policies to reflect the influence of AI authoring tools.

The consensus is that AI has no place on the author byline.

https://www.mdedge.com/obgyn/article/263471/business-medicine/chatgpt-friend-or-foe-medical-publishing

Continue to: FROM THE JOURNALS...

FROM THE JOURNALS

Review supports continued mask-wearing in health care visits

Jay Croft

A new study urges people to continue wearing protective masks in medical settings, even though the U.S. public health emergency declaration around COVID-19 has expired.

Masks continue to lower the risk of catching the virus during medical visits, according to the study, published in Annals of Internal Medicine. And there was not much difference between wearing surgical masks and N95 respirators in health care settings.

The researchers reviewed 3 randomized trials and 21 observational studies to compare the effectiveness of those and cloth masks in reducing COVID-19 transmission.

“Masking in interactions between patients and health care personnel should continue to receive serious consideration as a patient safety measure,” Tara N. Palmore, MD, of George Washington University, Washington, and David K. Henderson, MD, of the National Institutes of Health, Bethesda, Md., wrote in an opinion article accompanying the study.

“In our enthusiasm to return to the appearance and feeling of normalcy, and as institutions decide which mitigation strategies to discontinue, we strongly advocate not discarding this important lesson learned for the sake of our patients’ safety,” Dr. Palmore and Dr. Henderson wrote.

Surgical masks limit the spread of aerosols and droplets from people who have the flu, coronaviruses or other respiratory viruses, CNN reported. And while masks are not 100% effective, they substantially lower the amount of virus put into the air via coughing and talking.

https://www.mdedge.com/obgyn/covid-19-updates

CONFERENCE COVERAGE

A ‘one-stop shop’: New guidance on hormones and aging

Miriam E. Tucker

A new statement from the Endocrine Society on hormones and aging highlights the differences between normal aging and disease, and when treatment is and isn’t appropriate.

The idea of the statement “is to be complete, but also to clarify some misunderstandings. ...We tried to be very clear in the language about what we know, where we can go, where we shouldn’t go, and what we still need to learn,” statement coauthor Cynthia A. Stuenkel, MD, of the University of California, San Diego, said in an interview.

The document is divided into nine parts or axes: growth hormone, adrenal, ovarian, testicular, thyroid, osteoporosis, vitamin D deficiency, type 2 diabetes, and water metabolism. Each section covers natural history and observational data in older individuals, available therapies, clinical trial data on efficacy and safety in older individuals, bulleted “key points,” and research gaps.

“Hormones and Aging: An Endocrine Society Scientific Statement” was presented at the annual meeting of the Endocrine Society and published online in the Journal of Clinical Endocrinology & Metabolism.

During a press briefing, writing group chair Anne R. Cappola, MD, of the University of Pennsylvania, Philadelphia, said the goal is to “provide a really concise summary across each of these areas. ... There are multiple hormonal changes that occur with age, so we really couldn’t limit ourselves to just one gland or the few that we commonly think about. We wanted to cover all the axes.”

The statement tackles several controversial areas, including hormone therapy for menopausal symptoms in women and hypogonadal symptoms in men and diabetes treatment goals in older adults.

“Hormones have these almost mythical qualities to some people. ... ‘If I just had my hormones back the way they were, it would all work out.’ What we want to do is make sure that patients are being treated appropriately and that their symptoms are being heard and managed and ascribed to the appropriate problems and not necessarily to hormonal problems when they are not. ... Part of what we need to do is [provide] the evidence that we have, which includes evidence of when not to prescribe as well as [when] to prescribe,” Dr. Cappola said.

https://www.mdedge.com/obgyn/conference-coverage ●

The risks of common postpartum mental health (PMH) problems may soon be more predictable, thanks to a new comprehensive index for identifying mothers’ 1-year risk at time of delivery.

Developed by Canadian researchers, the easily implementable PMH CAREPLAN index “creates a framework for clinically actionable risk stratification that could assist patients and providers in determining an individual’s level of risk for common postpartum mental health disorders and direct them to appropriate intervention,” wrote a group led by Simone N. Vigod, MD, MSc, head of the department of psychiatry at Women’s College Hospital, Toronto, in the British Journal of Psychiatry.

courtesy Women&#039;s College Hospital

After giving birth, women are especially vulnerable to major depression, anxiety, PTSD, and obsessive-compulsive disorder, which have a general postpartum prevalence of 7%-20%.

Common PMH disorders are to be distinguished from the more rare but severe PMH disorders such as postpartum psychosis and bipolar disorder, the researchers stressed.

“We know there are interventions that can prevent these disorders, but these seem to work best in people who are at high risk for developing the illnesses, “ Dr. Vigod said. “So, we wanted to be able to determine the level of risk that a person might actually experience them.”

In an ideal world, she continued, physicians might be able to say to a patient: “You have a 50% chance of developing postpartum depression and anxiety, so it may be worth investing your time and resources in a course of preventive psychotherapy.” Or: “You have a 90% chance of developing these disorders, so it might be worth going back on your medications even though you are breastfeeding.” Or: “You have only a 1% chance of developing them, so probably it’s not worthwhile to go back on your medication prophylactically.”

A need for a new assessment tool, akin to the Framingham Risk Score for 10-year cardiovascular events and the FRAX scoring system for 10-year fracture risk, was evident since previous indices based largely on patient self-reporting have had moderate predictive capacity, and have not been adopted in clinical practice, Dr. Vigod and associates noted.
 

Split-cohort design

Using population-based health administrative data and hospital birth records from Ontario during 2012-2015, Dr. Vigod’s group created and internally validated a predictive model for common PMH disorders in a cohort of 152,362 mothers. They then converted it to a risk index after validation in an additional cohort of 75,772 mothers. The women had delivered live infants during 2012-2014.

A common PMH disorder occurred in 13,608 mothers, while 214,526 were unaffected.

Independently associated PMH variables were many: prenatal care provider, mental health diagnosis history and medications during pregnancy, psychiatric hospital admissions or ED visits, conception type and complications, and apprehension of newborn by child services. Other factors were region of maternal origin, extremes of gestational age at birth, primary maternal language, lactation intention, maternal age, and number of prenatal visits.

Based on a broad span of scores from 0 to 39, 1-year common PMH disorder risk ranged from 1.5% to 40.5%, with an overall 1-year prevalence of 6%, consistent with previous studies. That included 11,262 (5%) mothers with an anxiety or related disorder, 3,392 (1.5%) with a depressive episode, and 1,046 (0.5%) with both. The best trade-off of sensitivity/specificity for risk appeared to be at a screening threshold score of 17 or above.
 

Risk drivers

PMH-affected mothers were slightly younger than unaffected women (mean age, 29.9 years vs. 30.6 years), more likely to be primiparous (45.2% vs. 42%), and less likely to be recent immigrants (16.7% vs. 27.2%).

They were also more likely to have previously experienced postpartum depression (4.4% vs. 1.4%), any depression (15.3% vs. 4.4%), and any anxiety disorder (13.8% vs. 4.3%).

As to lifestyle, smoking was more common in women with PMH (15.0% vs. 10.2%), as were the use of nonprescribed substances (3% vs. 1.4%) and intimate partner violence in pregnancy (2.7% vs. 1.5%).

In addition, the affected group experienced more pregnancy complications than their unaffected peers (16% vs. 13.9%), preterm birth (8.2% vs. 6.8%), and Apgar scores below 7 at 1 or 5 minutes (10.5% vs. 7.6%).

Low income did not appear to have an impact since just over 20% in either group fell into the lowest neighborhood income quintile.

courtesy Northwestern Medicine

Commenting on the index but not involved in developing it, LaTasha D. Nelson, MD, an associate professor or medicine and a maternal-fetal medicine specialist at Northwestern Medicine in Chicago, doubted the Canadian model would work as well in the more fragmented U.S. health care system, compared with Canada’s universal model with its large provincial health databases.

She also found the large number of variables and broad score range potentially problematic, especially if the risk threshold is set at less than half the maximum score at 17, at which some low-risk mothers might get screening and perhaps intervention. “Are we going to use up the resources we have for those who might not need help, or are we going to treat someone who really needs it?” she asked.

Another concern is the postpartum timing of assessment. At Dr. Nelson’s center, mothers are checked for mental health at two points during pregnancy and those with higher scores are triaged for further care.

Dr. Nelson was also puzzled by the score-lowering impact of prenatal care given by a nurse practitioner and “other” provider : –5 and –2, respectively, versus +3 for a midwife and +1 for a family doctor. “This may capture more relaxed, easy-going multiparous mothers who felt comfortable turning to an NP,” she said.

It may indeed reflect that the risk level of a person who sees those providers is overall lower, Dr. Vigod agreed. “This is one reason why we would want to see replication of these results in other jurisdictions and by other ways of diagnosis before putting it out into clinical practice.”

As to the score-lowering effect of not speaking English as the primary tongue, Dr. Nelson wondered, “is that because we’re taking better care of mothers who speak the main language and missing those who speak other languages? Are they not getting the same level of interrogation?”

It may be that individuals in these groups were less likely to access mental health care, Dr. Vigod agreed, or it might reflect the so-called healthy immigrant effect or culturally different levels of postpartum support. “It might mean that there are more people who benefit from community-level protective factors in these groups. We know that social support is an important protective factor.”

Despite her reservations about the index, Dr. Nelson said that increasing attention to the pre- and postnatal mental health of mothers is an important part of maternal care. “This is an issue that needs to be recognized.”

The next step, Dr. Vigod said, is to determine whether the index holds up in other populations. “Then, we would want to test it out to see if recommending interventions based on a certain level of risk improves outcomes. At what percentage risk would starting an antidepressant medication result in a reduced risk for postpartum depression or anxiety – 90%, 80%, 70%, or less?”

The study received funding from the Canadian Institutes of Health Research. Data were analyzed by ICES, an independent nonprofit research organization that holds population-based data. Dr. Vigod reported royalties from UpToDate for materials related to depression and pregnancy. Dr. Nelson disclosed no relevant competing interests.

The risks of common postpartum mental health (PMH) problems may soon be more predictable, thanks to a new comprehensive index for identifying mothers’ 1-year risk at time of delivery.

Developed by Canadian researchers, the easily implementable PMH CAREPLAN index “creates a framework for clinically actionable risk stratification that could assist patients and providers in determining an individual’s level of risk for common postpartum mental health disorders and direct them to appropriate intervention,” wrote a group led by Simone N. Vigod, MD, MSc, head of the department of psychiatry at Women’s College Hospital, Toronto, in the British Journal of Psychiatry.

courtesy Women&#039;s College Hospital

After giving birth, women are especially vulnerable to major depression, anxiety, PTSD, and obsessive-compulsive disorder, which have a general postpartum prevalence of 7%-20%.

Common PMH disorders are to be distinguished from the more rare but severe PMH disorders such as postpartum psychosis and bipolar disorder, the researchers stressed.

“We know there are interventions that can prevent these disorders, but these seem to work best in people who are at high risk for developing the illnesses, “ Dr. Vigod said. “So, we wanted to be able to determine the level of risk that a person might actually experience them.”

In an ideal world, she continued, physicians might be able to say to a patient: “You have a 50% chance of developing postpartum depression and anxiety, so it may be worth investing your time and resources in a course of preventive psychotherapy.” Or: “You have a 90% chance of developing these disorders, so it might be worth going back on your medications even though you are breastfeeding.” Or: “You have only a 1% chance of developing them, so probably it’s not worthwhile to go back on your medication prophylactically.”

A need for a new assessment tool, akin to the Framingham Risk Score for 10-year cardiovascular events and the FRAX scoring system for 10-year fracture risk, was evident since previous indices based largely on patient self-reporting have had moderate predictive capacity, and have not been adopted in clinical practice, Dr. Vigod and associates noted.
 

Split-cohort design

Using population-based health administrative data and hospital birth records from Ontario during 2012-2015, Dr. Vigod’s group created and internally validated a predictive model for common PMH disorders in a cohort of 152,362 mothers. They then converted it to a risk index after validation in an additional cohort of 75,772 mothers. The women had delivered live infants during 2012-2014.

A common PMH disorder occurred in 13,608 mothers, while 214,526 were unaffected.

Independently associated PMH variables were many: prenatal care provider, mental health diagnosis history and medications during pregnancy, psychiatric hospital admissions or ED visits, conception type and complications, and apprehension of newborn by child services. Other factors were region of maternal origin, extremes of gestational age at birth, primary maternal language, lactation intention, maternal age, and number of prenatal visits.

Based on a broad span of scores from 0 to 39, 1-year common PMH disorder risk ranged from 1.5% to 40.5%, with an overall 1-year prevalence of 6%, consistent with previous studies. That included 11,262 (5%) mothers with an anxiety or related disorder, 3,392 (1.5%) with a depressive episode, and 1,046 (0.5%) with both. The best trade-off of sensitivity/specificity for risk appeared to be at a screening threshold score of 17 or above.
 

Risk drivers

PMH-affected mothers were slightly younger than unaffected women (mean age, 29.9 years vs. 30.6 years), more likely to be primiparous (45.2% vs. 42%), and less likely to be recent immigrants (16.7% vs. 27.2%).

They were also more likely to have previously experienced postpartum depression (4.4% vs. 1.4%), any depression (15.3% vs. 4.4%), and any anxiety disorder (13.8% vs. 4.3%).

As to lifestyle, smoking was more common in women with PMH (15.0% vs. 10.2%), as were the use of nonprescribed substances (3% vs. 1.4%) and intimate partner violence in pregnancy (2.7% vs. 1.5%).

In addition, the affected group experienced more pregnancy complications than their unaffected peers (16% vs. 13.9%), preterm birth (8.2% vs. 6.8%), and Apgar scores below 7 at 1 or 5 minutes (10.5% vs. 7.6%).

Low income did not appear to have an impact since just over 20% in either group fell into the lowest neighborhood income quintile.

courtesy Northwestern Medicine

Commenting on the index but not involved in developing it, LaTasha D. Nelson, MD, an associate professor or medicine and a maternal-fetal medicine specialist at Northwestern Medicine in Chicago, doubted the Canadian model would work as well in the more fragmented U.S. health care system, compared with Canada’s universal model with its large provincial health databases.

She also found the large number of variables and broad score range potentially problematic, especially if the risk threshold is set at less than half the maximum score at 17, at which some low-risk mothers might get screening and perhaps intervention. “Are we going to use up the resources we have for those who might not need help, or are we going to treat someone who really needs it?” she asked.

Another concern is the postpartum timing of assessment. At Dr. Nelson’s center, mothers are checked for mental health at two points during pregnancy and those with higher scores are triaged for further care.

Dr. Nelson was also puzzled by the score-lowering impact of prenatal care given by a nurse practitioner and “other” provider : –5 and –2, respectively, versus +3 for a midwife and +1 for a family doctor. “This may capture more relaxed, easy-going multiparous mothers who felt comfortable turning to an NP,” she said.

It may indeed reflect that the risk level of a person who sees those providers is overall lower, Dr. Vigod agreed. “This is one reason why we would want to see replication of these results in other jurisdictions and by other ways of diagnosis before putting it out into clinical practice.”

As to the score-lowering effect of not speaking English as the primary tongue, Dr. Nelson wondered, “is that because we’re taking better care of mothers who speak the main language and missing those who speak other languages? Are they not getting the same level of interrogation?”

It may be that individuals in these groups were less likely to access mental health care, Dr. Vigod agreed, or it might reflect the so-called healthy immigrant effect or culturally different levels of postpartum support. “It might mean that there are more people who benefit from community-level protective factors in these groups. We know that social support is an important protective factor.”

Despite her reservations about the index, Dr. Nelson said that increasing attention to the pre- and postnatal mental health of mothers is an important part of maternal care. “This is an issue that needs to be recognized.”

The next step, Dr. Vigod said, is to determine whether the index holds up in other populations. “Then, we would want to test it out to see if recommending interventions based on a certain level of risk improves outcomes. At what percentage risk would starting an antidepressant medication result in a reduced risk for postpartum depression or anxiety – 90%, 80%, 70%, or less?”

The study received funding from the Canadian Institutes of Health Research. Data were analyzed by ICES, an independent nonprofit research organization that holds population-based data. Dr. Vigod reported royalties from UpToDate for materials related to depression and pregnancy. Dr. Nelson disclosed no relevant competing interests.

The risks of common postpartum mental health (PMH) problems may soon be more predictable, thanks to a new comprehensive index for identifying mothers’ 1-year risk at time of delivery.

Developed by Canadian researchers, the easily implementable PMH CAREPLAN index “creates a framework for clinically actionable risk stratification that could assist patients and providers in determining an individual’s level of risk for common postpartum mental health disorders and direct them to appropriate intervention,” wrote a group led by Simone N. Vigod, MD, MSc, head of the department of psychiatry at Women’s College Hospital, Toronto, in the British Journal of Psychiatry.

courtesy Women&#039;s College Hospital

After giving birth, women are especially vulnerable to major depression, anxiety, PTSD, and obsessive-compulsive disorder, which have a general postpartum prevalence of 7%-20%.

Common PMH disorders are to be distinguished from the more rare but severe PMH disorders such as postpartum psychosis and bipolar disorder, the researchers stressed.

“We know there are interventions that can prevent these disorders, but these seem to work best in people who are at high risk for developing the illnesses, “ Dr. Vigod said. “So, we wanted to be able to determine the level of risk that a person might actually experience them.”

In an ideal world, she continued, physicians might be able to say to a patient: “You have a 50% chance of developing postpartum depression and anxiety, so it may be worth investing your time and resources in a course of preventive psychotherapy.” Or: “You have a 90% chance of developing these disorders, so it might be worth going back on your medications even though you are breastfeeding.” Or: “You have only a 1% chance of developing them, so probably it’s not worthwhile to go back on your medication prophylactically.”

A need for a new assessment tool, akin to the Framingham Risk Score for 10-year cardiovascular events and the FRAX scoring system for 10-year fracture risk, was evident since previous indices based largely on patient self-reporting have had moderate predictive capacity, and have not been adopted in clinical practice, Dr. Vigod and associates noted.
 

Split-cohort design

Using population-based health administrative data and hospital birth records from Ontario during 2012-2015, Dr. Vigod’s group created and internally validated a predictive model for common PMH disorders in a cohort of 152,362 mothers. They then converted it to a risk index after validation in an additional cohort of 75,772 mothers. The women had delivered live infants during 2012-2014.

A common PMH disorder occurred in 13,608 mothers, while 214,526 were unaffected.

Independently associated PMH variables were many: prenatal care provider, mental health diagnosis history and medications during pregnancy, psychiatric hospital admissions or ED visits, conception type and complications, and apprehension of newborn by child services. Other factors were region of maternal origin, extremes of gestational age at birth, primary maternal language, lactation intention, maternal age, and number of prenatal visits.

Based on a broad span of scores from 0 to 39, 1-year common PMH disorder risk ranged from 1.5% to 40.5%, with an overall 1-year prevalence of 6%, consistent with previous studies. That included 11,262 (5%) mothers with an anxiety or related disorder, 3,392 (1.5%) with a depressive episode, and 1,046 (0.5%) with both. The best trade-off of sensitivity/specificity for risk appeared to be at a screening threshold score of 17 or above.
 

Risk drivers

PMH-affected mothers were slightly younger than unaffected women (mean age, 29.9 years vs. 30.6 years), more likely to be primiparous (45.2% vs. 42%), and less likely to be recent immigrants (16.7% vs. 27.2%).

They were also more likely to have previously experienced postpartum depression (4.4% vs. 1.4%), any depression (15.3% vs. 4.4%), and any anxiety disorder (13.8% vs. 4.3%).

As to lifestyle, smoking was more common in women with PMH (15.0% vs. 10.2%), as were the use of nonprescribed substances (3% vs. 1.4%) and intimate partner violence in pregnancy (2.7% vs. 1.5%).

In addition, the affected group experienced more pregnancy complications than their unaffected peers (16% vs. 13.9%), preterm birth (8.2% vs. 6.8%), and Apgar scores below 7 at 1 or 5 minutes (10.5% vs. 7.6%).

Low income did not appear to have an impact since just over 20% in either group fell into the lowest neighborhood income quintile.

courtesy Northwestern Medicine

Commenting on the index but not involved in developing it, LaTasha D. Nelson, MD, an associate professor or medicine and a maternal-fetal medicine specialist at Northwestern Medicine in Chicago, doubted the Canadian model would work as well in the more fragmented U.S. health care system, compared with Canada’s universal model with its large provincial health databases.

She also found the large number of variables and broad score range potentially problematic, especially if the risk threshold is set at less than half the maximum score at 17, at which some low-risk mothers might get screening and perhaps intervention. “Are we going to use up the resources we have for those who might not need help, or are we going to treat someone who really needs it?” she asked.

Another concern is the postpartum timing of assessment. At Dr. Nelson’s center, mothers are checked for mental health at two points during pregnancy and those with higher scores are triaged for further care.

Dr. Nelson was also puzzled by the score-lowering impact of prenatal care given by a nurse practitioner and “other” provider : –5 and –2, respectively, versus +3 for a midwife and +1 for a family doctor. “This may capture more relaxed, easy-going multiparous mothers who felt comfortable turning to an NP,” she said.

It may indeed reflect that the risk level of a person who sees those providers is overall lower, Dr. Vigod agreed. “This is one reason why we would want to see replication of these results in other jurisdictions and by other ways of diagnosis before putting it out into clinical practice.”

As to the score-lowering effect of not speaking English as the primary tongue, Dr. Nelson wondered, “is that because we’re taking better care of mothers who speak the main language and missing those who speak other languages? Are they not getting the same level of interrogation?”

It may be that individuals in these groups were less likely to access mental health care, Dr. Vigod agreed, or it might reflect the so-called healthy immigrant effect or culturally different levels of postpartum support. “It might mean that there are more people who benefit from community-level protective factors in these groups. We know that social support is an important protective factor.”

Despite her reservations about the index, Dr. Nelson said that increasing attention to the pre- and postnatal mental health of mothers is an important part of maternal care. “This is an issue that needs to be recognized.”

The next step, Dr. Vigod said, is to determine whether the index holds up in other populations. “Then, we would want to test it out to see if recommending interventions based on a certain level of risk improves outcomes. At what percentage risk would starting an antidepressant medication result in a reduced risk for postpartum depression or anxiety – 90%, 80%, 70%, or less?”

The study received funding from the Canadian Institutes of Health Research. Data were analyzed by ICES, an independent nonprofit research organization that holds population-based data. Dr. Vigod reported royalties from UpToDate for materials related to depression and pregnancy. Dr. Nelson disclosed no relevant competing interests.

Obesity is a major health problem in the United States. The Centers for Disease Control and Prevention (CDC) defines the problem as weight that is higher than what is healthy for a given height, with quantitative definitions of overweight and obesity as body mass indices (BMIs) of 25 to 29.9 kg/m² and ≥ 30 kg/m², respectively.¹ The prevalence of obesity among adults in 2017 ̶ 2018 was reported by the CDC to be 42.4%.² Among women, the reported prevalence of obesity was lowest among Asian individuals (17.2%) and greatest among non-Hispanic Black individuals (56.9%), with White (39.8%) and Hispanic individuals (43.7%) having rates in between.² In a meta-analysis of prospective studies that included 4 million people who were never smokers and had no chronic disease at baseline, age- and sex-adjusted mortality rates were studied over a median of 14 years of follow-up.³ Compared with those with a BMI of 20 to 25 kg/m², people with a BMI of 30 to 34.9 kg/m² or a BMI of 35 to 39.9 kg/m² had increased risks of death of 46% and 94%, respectively, demonstrating that obesity increases this risk.³

The increased risk of death associated with obesity is caused by obesity-related diseases that cause early mortality, including diabetes mellitus (DM), dyslipidemia, hypertension, coronary heart disease, heart failure, atrial fibrillation, stroke, and venous thromboembolic events.⁴ Obesity is also associated with an increased risk of many cancers, including cancer of the endometrium, kidney, esophagus, stomach, colon, rectum, gallbladder, pancreas, liver, and breast.⁵ With regard to gynecologic disease, obesity is associated with an increased risk of fibroids and heavy menstrual bleeding.⁶ For pregnant patients, obesity is associated with increased risks of⁷:

• miscarriage and stillbirth
• preeclampsia and gestational hypertension
• gestational diabetes
• severe maternal morbidity
• postterm pregnancy
• venous thromboembolism
• endometritis.

For obese patients, weight loss can normalize blood pressure, reduce the risk of cardiovascular events, decrease the risk of cancer, and cure type 2 DM.⁸

Bariatric surgery: The gold standard treatment for reliable and sustained weight loss

All patients with obesity should be counseled to reduce caloric intake and increase physical activity. Dietary counseling provided by a nutritionist may help reinforce advice given by a provider. However, lifestyle interventions are associated with modest weight loss (<5% of bodyweight; FIGURE).⁹ The gold standard treatment for reliable and sustained weight loss is bariatric surgery.

In the Swedish Obese Subjects study, involving 2,010 people, following bariatric surgery the mean decrease in bodyweight was 23% at 2 years, with a slow increase in weight thereafter, resulting in a sustained mean weight loss of 18% at 10 years.⁸ In this study, people in the diet and exercise control group had no change in bodyweight over 10 years of follow-up.⁸ Not all eligible obese patients want to undergo bariatric surgery because it is an arduous sequential process involving 6 months of intensive preoperative preparation, bariatric surgery, recovery, and intensive postoperative follow-up. The perioperative mortality rate is 0.03% to 0.2%.¹⁰ Following bariatric surgery, additional operations may be necessary for more than 10% of patients.¹⁰ With recent breakthroughs in the medication management of obesity, patients who do not want bariatric surgery can achieve reliable weight loss of greater than 10% of body weight with glucagon-like peptide -1 (GLP-1) agonists.

ILLUSTRATION: KIMBERLY MARTENS FOR OBG MANAGEMENT

GLP-1 agonist analogues: Practice-changing breakthrough in medication treatment

GLP-1, a 30 amino acid peptide, is produced by intestinal enteroendocrine cells and neurons in the medulla and hypothalamus.¹¹ GLP-1 reduces hunger cravings and causes satiety, reducing daily food intake.¹² GLP-1 also enhances the secretion of insulin, making GLP-1 agonists an effective treatment for type 2 DM. In humans and experimental animals, the administration of exogenous GLP-1 agonists decreases hunger cravings and causes satiety, reducing food intake, resulting in weight loss.¹² The synthetic GLP-1 agonists, liraglutide (Saxenda) and semaglutide (Wegovy) are approved by the US Food and Drug Administration (FDA) as anti-obesity medications.

Native GLP-1 has a short circulating half-life of approximately 2 minutes. The synthetic GLP-1 agonist medications liraglutide and semaglutide are modified to significantly increase their half-life. Liraglutide is a modified version of GLP-1 with a palmitic acid side chain and an amino acid spacer resulting in reduced degradation and a 15-hour half-life, necessitating daily administration. Semaglutide has a steric acid diacid at Lys26, a large synthetic spacer, a modification of amino acid 8 with the addition of α-aminobutyric acid and a 165-hour half-life, permitting weekly administration.¹³ For weight loss, liraglutide and semaglultide are administered by subcutaneous injection. Tirzepatide (Mounjaro) is a novel GLP-1 agonist. It is also a gastric inhibitory peptide, is FDA approved to treat type 2 DM, and is awaiting FDA approval as a weight loss medication.Tirzepatide causes substantial weight loss, similar to the effect of semaglutide.¹⁴

Semaglutide and weight loss

Semaglutide is approved by the FDA for chronic weight management as an adjunct to a reduced-calorie diet and increased physical activity in adults with a BMI ≥ 30 kg/m² or ≥ 27 kg/m² in the presence of a weight-related comorbidity. It is also FDA approved to treat type 2 DM.

In a weight loss trial, 1,961 overweight and obese patients with a mean BMI of 38 kg/m², were randomly assigned to semaglutide or placebo treatment for 68 weeks. All the participants were following a regimen that included a calorie-reduced diet and increased physical activity. The mean changes in body weight for the patients in the semaglutide and placebo treatment groups were -14.9% and -2.4%, respectively. The treatment difference was -12.4% (95% confidence interval [CI], -13.4% to -11.5%; P <.001). In this study, compared with placebo, semaglutide treatment resulted in a greater decrease in waist circumference, -5.3 in versus -1.6 in.¹⁵ A network meta-analysis of the efficacy of weight loss medicines indicates that semaglutide is the most effective medication currently FDA approved for weight loss, reliably producing substantial weight loss (FIGURE).⁹

In one randomized clinical trial, investigators directly compared the efficacy of semaglutide and liraglutide in achieving weight loss. In this trial, 338 patients were assigned randomly to treatment with semaglutide 2.4 mg weekly subcutaneous injection, liraglutide 3.0 mg daily subcutaneous injection, or placebo. All the participants were following a regimen that included a calorie-reduced diet and increased physical activity.¹⁶ After 68 weeks of treatment, the mean weight changes were -15.8%, -6.4%, and -1.9% in the semaglutide, liraglutide, and placebo groups, respectively. The difference between the semaglutide and liraglutide groups was -9.4% (95% CI, -12% to -6.8%; P <.001).¹⁶

Continue to: Semaglutide dose-escalation and contraindications...

For weight loss, the target dose of semaglutide is 2.4 mg once weekly subcutaneous injection achieved by sequential dose escalation. To give patients time to adjust to adverse effects caused by the medication, a standardized dose-escalation regimen is recommended. The FDA-approved escalation regimen for semaglutide treatment begins with a weekly subcutaneous dose of 0.25 mg for 4 weeks, followed by an increase in the weekly dosage every 4 weeks: 0.5 mg, 1.0 mg, 1.7 mg, and 2.4 mg.¹⁷ To support the dose-escalation process there are 5 unique autoinjectors that deliver the appropriate dose for the current step.

Semaglutide is contraindicated if the patient has an allergy to the medication or if there is a personal or family history of medullary thyroid cancer.¹⁷ In animal toxicology studies, semaglutide at clinically relevant dosing was associated with an increased risk of developing medullary thyroid cancer. Patients with a personal history of multiple endocrine neoplasia syndrome type 2, (medullary thyroid cancer, pheochromocytoma, and primary hyperparathyroidism) should not take semaglutide. Semaglutide may cause fetal harm and the FDA recommends discontinuing semaglutide at least 2 months before pregnancy.¹⁷ According to the FDA, the safety of semaglutide during breastfeeding has not been established. In Canada, breastfeeding is a contraindication to semaglutide treatment.¹⁸

Limitations of medication treatment of obesity

There are important limitations to semaglutide treatment of obesity, including:

• weight gain after stopping treatment
• limited medical insurance supportfor an expensive medication treatment
• bothersome adverse effects.

Weight gain posttreatment. After stopping medication treatment of obesity, weight gain occurs in most patients. However, patients may remain below baseline weight for a long time after stopping medication therapy. In one trial of 803 patients, after 20 weeks of semaglutide treatment (16-week dose-escalation phase, followed by 4 weeks on a weekly dose of 2.4 mg), the participants were randomized to 48 additional weeks of semaglutide or placebo.¹⁹ All the participants were following a regimen that included a calorie-reduced diet and increased physical activity. At the initial 20 weeks of treatment time point the mean weight change was -10.6%. Over the following 48 weeks, the patients treated with semaglutidehad an additional mean weight change of -7.9%, while the mean weight change for the placebo group was +6.9%.

Medical insurance coverage. A major barrier to semaglutide treatment of obesity is the medication’s cost. At the website GoodRx (https://www.goodrx.com/), the estimated price for a 1-month supply of semaglutide (Wegovy) is $1,350.²⁰ By contrast, a 1-month supply of phentermine-topiramate (Qsymia) is approximately $205. Currently, many medical insurance plans do not cover the cost of semaglutide treatment for weight loss. Patent protection for liraglutide may expire in the next few years, permitting the marketing of a lower-cost generic formulation, increasing the availability of the medication. However, as noted above, compared with liraglutide, semaglutide treatment results in much greater weight loss.

The most common adverse effects associated with semaglutide treatment are nausea, vomiting, diarrhea, and constipation. In one randomized clinical trial involving 1,961 patients, the frequency of adverse effects reported by patients taking semaglutide incrementally above the frequency of the same adverse effect reported by patients on placebo was: nausea (27%), vomiting (18%), diarrhea (16%), constipation (14%), dyspepsia (7%), and abdominal pain (5%).¹⁵ In this study, treatment was discontinued due to adverse effects in 7% and 3% of the patients in the semaglutide and placebo groups, respectively. Experts believe that adverse effects can be minimized by increasing the dose slowly and decreasing the dose if adverse effects are bothersome to the patient.

Measuring the benefits of semaglutide weight loss

Overweight and obesity are prevalent problems with many adverse consequences, including an increased risk of death. In population studies, weight loss following bariatric surgery is associated with a substantial reduction in mortality, cancer, and heart disease compared with conventional therapy.²¹ Over the next few years, the effect of semaglutide-induced weight loss on the rate of cancer and heart disease should become clear. If semaglutide treatment of obesity is associated with a reduction in cancer and heart disease, it would be a truly breakthrough medication. ●

Obesity is a major health problem in the United States. The Centers for Disease Control and Prevention (CDC) defines the problem as weight that is higher than what is healthy for a given height, with quantitative definitions of overweight and obesity as body mass indices (BMIs) of 25 to 29.9 kg/m² and ≥ 30 kg/m², respectively.¹ The prevalence of obesity among adults in 2017 ̶ 2018 was reported by the CDC to be 42.4%.² Among women, the reported prevalence of obesity was lowest among Asian individuals (17.2%) and greatest among non-Hispanic Black individuals (56.9%), with White (39.8%) and Hispanic individuals (43.7%) having rates in between.² In a meta-analysis of prospective studies that included 4 million people who were never smokers and had no chronic disease at baseline, age- and sex-adjusted mortality rates were studied over a median of 14 years of follow-up.³ Compared with those with a BMI of 20 to 25 kg/m², people with a BMI of 30 to 34.9 kg/m² or a BMI of 35 to 39.9 kg/m² had increased risks of death of 46% and 94%, respectively, demonstrating that obesity increases this risk.³

The increased risk of death associated with obesity is caused by obesity-related diseases that cause early mortality, including diabetes mellitus (DM), dyslipidemia, hypertension, coronary heart disease, heart failure, atrial fibrillation, stroke, and venous thromboembolic events.⁴ Obesity is also associated with an increased risk of many cancers, including cancer of the endometrium, kidney, esophagus, stomach, colon, rectum, gallbladder, pancreas, liver, and breast.⁵ With regard to gynecologic disease, obesity is associated with an increased risk of fibroids and heavy menstrual bleeding.⁶ For pregnant patients, obesity is associated with increased risks of⁷:

• miscarriage and stillbirth
• preeclampsia and gestational hypertension
• gestational diabetes
• severe maternal morbidity
• postterm pregnancy
• venous thromboembolism
• endometritis.

For obese patients, weight loss can normalize blood pressure, reduce the risk of cardiovascular events, decrease the risk of cancer, and cure type 2 DM.⁸

Bariatric surgery: The gold standard treatment for reliable and sustained weight loss

All patients with obesity should be counseled to reduce caloric intake and increase physical activity. Dietary counseling provided by a nutritionist may help reinforce advice given by a provider. However, lifestyle interventions are associated with modest weight loss (<5% of bodyweight; FIGURE).⁹ The gold standard treatment for reliable and sustained weight loss is bariatric surgery.

In the Swedish Obese Subjects study, involving 2,010 people, following bariatric surgery the mean decrease in bodyweight was 23% at 2 years, with a slow increase in weight thereafter, resulting in a sustained mean weight loss of 18% at 10 years.⁸ In this study, people in the diet and exercise control group had no change in bodyweight over 10 years of follow-up.⁸ Not all eligible obese patients want to undergo bariatric surgery because it is an arduous sequential process involving 6 months of intensive preoperative preparation, bariatric surgery, recovery, and intensive postoperative follow-up. The perioperative mortality rate is 0.03% to 0.2%.¹⁰ Following bariatric surgery, additional operations may be necessary for more than 10% of patients.¹⁰ With recent breakthroughs in the medication management of obesity, patients who do not want bariatric surgery can achieve reliable weight loss of greater than 10% of body weight with glucagon-like peptide -1 (GLP-1) agonists.

ILLUSTRATION: KIMBERLY MARTENS FOR OBG MANAGEMENT

GLP-1 agonist analogues: Practice-changing breakthrough in medication treatment

GLP-1, a 30 amino acid peptide, is produced by intestinal enteroendocrine cells and neurons in the medulla and hypothalamus.¹¹ GLP-1 reduces hunger cravings and causes satiety, reducing daily food intake.¹² GLP-1 also enhances the secretion of insulin, making GLP-1 agonists an effective treatment for type 2 DM. In humans and experimental animals, the administration of exogenous GLP-1 agonists decreases hunger cravings and causes satiety, reducing food intake, resulting in weight loss.¹² The synthetic GLP-1 agonists, liraglutide (Saxenda) and semaglutide (Wegovy) are approved by the US Food and Drug Administration (FDA) as anti-obesity medications.

Native GLP-1 has a short circulating half-life of approximately 2 minutes. The synthetic GLP-1 agonist medications liraglutide and semaglutide are modified to significantly increase their half-life. Liraglutide is a modified version of GLP-1 with a palmitic acid side chain and an amino acid spacer resulting in reduced degradation and a 15-hour half-life, necessitating daily administration. Semaglutide has a steric acid diacid at Lys26, a large synthetic spacer, a modification of amino acid 8 with the addition of α-aminobutyric acid and a 165-hour half-life, permitting weekly administration.¹³ For weight loss, liraglutide and semaglultide are administered by subcutaneous injection. Tirzepatide (Mounjaro) is a novel GLP-1 agonist. It is also a gastric inhibitory peptide, is FDA approved to treat type 2 DM, and is awaiting FDA approval as a weight loss medication.Tirzepatide causes substantial weight loss, similar to the effect of semaglutide.¹⁴

Semaglutide and weight loss

Semaglutide is approved by the FDA for chronic weight management as an adjunct to a reduced-calorie diet and increased physical activity in adults with a BMI ≥ 30 kg/m² or ≥ 27 kg/m² in the presence of a weight-related comorbidity. It is also FDA approved to treat type 2 DM.

In a weight loss trial, 1,961 overweight and obese patients with a mean BMI of 38 kg/m², were randomly assigned to semaglutide or placebo treatment for 68 weeks. All the participants were following a regimen that included a calorie-reduced diet and increased physical activity. The mean changes in body weight for the patients in the semaglutide and placebo treatment groups were -14.9% and -2.4%, respectively. The treatment difference was -12.4% (95% confidence interval [CI], -13.4% to -11.5%; P <.001). In this study, compared with placebo, semaglutide treatment resulted in a greater decrease in waist circumference, -5.3 in versus -1.6 in.¹⁵ A network meta-analysis of the efficacy of weight loss medicines indicates that semaglutide is the most effective medication currently FDA approved for weight loss, reliably producing substantial weight loss (FIGURE).⁹

In one randomized clinical trial, investigators directly compared the efficacy of semaglutide and liraglutide in achieving weight loss. In this trial, 338 patients were assigned randomly to treatment with semaglutide 2.4 mg weekly subcutaneous injection, liraglutide 3.0 mg daily subcutaneous injection, or placebo. All the participants were following a regimen that included a calorie-reduced diet and increased physical activity.¹⁶ After 68 weeks of treatment, the mean weight changes were -15.8%, -6.4%, and -1.9% in the semaglutide, liraglutide, and placebo groups, respectively. The difference between the semaglutide and liraglutide groups was -9.4% (95% CI, -12% to -6.8%; P <.001).¹⁶

Continue to: Semaglutide dose-escalation and contraindications...

For weight loss, the target dose of semaglutide is 2.4 mg once weekly subcutaneous injection achieved by sequential dose escalation. To give patients time to adjust to adverse effects caused by the medication, a standardized dose-escalation regimen is recommended. The FDA-approved escalation regimen for semaglutide treatment begins with a weekly subcutaneous dose of 0.25 mg for 4 weeks, followed by an increase in the weekly dosage every 4 weeks: 0.5 mg, 1.0 mg, 1.7 mg, and 2.4 mg.¹⁷ To support the dose-escalation process there are 5 unique autoinjectors that deliver the appropriate dose for the current step.

Semaglutide is contraindicated if the patient has an allergy to the medication or if there is a personal or family history of medullary thyroid cancer.¹⁷ In animal toxicology studies, semaglutide at clinically relevant dosing was associated with an increased risk of developing medullary thyroid cancer. Patients with a personal history of multiple endocrine neoplasia syndrome type 2, (medullary thyroid cancer, pheochromocytoma, and primary hyperparathyroidism) should not take semaglutide. Semaglutide may cause fetal harm and the FDA recommends discontinuing semaglutide at least 2 months before pregnancy.¹⁷ According to the FDA, the safety of semaglutide during breastfeeding has not been established. In Canada, breastfeeding is a contraindication to semaglutide treatment.¹⁸

Limitations of medication treatment of obesity

There are important limitations to semaglutide treatment of obesity, including:

• weight gain after stopping treatment
• limited medical insurance supportfor an expensive medication treatment
• bothersome adverse effects.

Weight gain posttreatment. After stopping medication treatment of obesity, weight gain occurs in most patients. However, patients may remain below baseline weight for a long time after stopping medication therapy. In one trial of 803 patients, after 20 weeks of semaglutide treatment (16-week dose-escalation phase, followed by 4 weeks on a weekly dose of 2.4 mg), the participants were randomized to 48 additional weeks of semaglutide or placebo.¹⁹ All the participants were following a regimen that included a calorie-reduced diet and increased physical activity. At the initial 20 weeks of treatment time point the mean weight change was -10.6%. Over the following 48 weeks, the patients treated with semaglutidehad an additional mean weight change of -7.9%, while the mean weight change for the placebo group was +6.9%.

Medical insurance coverage. A major barrier to semaglutide treatment of obesity is the medication’s cost. At the website GoodRx (https://www.goodrx.com/), the estimated price for a 1-month supply of semaglutide (Wegovy) is $1,350.²⁰ By contrast, a 1-month supply of phentermine-topiramate (Qsymia) is approximately $205. Currently, many medical insurance plans do not cover the cost of semaglutide treatment for weight loss. Patent protection for liraglutide may expire in the next few years, permitting the marketing of a lower-cost generic formulation, increasing the availability of the medication. However, as noted above, compared with liraglutide, semaglutide treatment results in much greater weight loss.

The most common adverse effects associated with semaglutide treatment are nausea, vomiting, diarrhea, and constipation. In one randomized clinical trial involving 1,961 patients, the frequency of adverse effects reported by patients taking semaglutide incrementally above the frequency of the same adverse effect reported by patients on placebo was: nausea (27%), vomiting (18%), diarrhea (16%), constipation (14%), dyspepsia (7%), and abdominal pain (5%).¹⁵ In this study, treatment was discontinued due to adverse effects in 7% and 3% of the patients in the semaglutide and placebo groups, respectively. Experts believe that adverse effects can be minimized by increasing the dose slowly and decreasing the dose if adverse effects are bothersome to the patient.

Measuring the benefits of semaglutide weight loss

Overweight and obesity are prevalent problems with many adverse consequences, including an increased risk of death. In population studies, weight loss following bariatric surgery is associated with a substantial reduction in mortality, cancer, and heart disease compared with conventional therapy.²¹ Over the next few years, the effect of semaglutide-induced weight loss on the rate of cancer and heart disease should become clear. If semaglutide treatment of obesity is associated with a reduction in cancer and heart disease, it would be a truly breakthrough medication. ●

Obesity is a major health problem in the United States. The Centers for Disease Control and Prevention (CDC) defines the problem as weight that is higher than what is healthy for a given height, with quantitative definitions of overweight and obesity as body mass indices (BMIs) of 25 to 29.9 kg/m² and ≥ 30 kg/m², respectively.¹ The prevalence of obesity among adults in 2017 ̶ 2018 was reported by the CDC to be 42.4%.² Among women, the reported prevalence of obesity was lowest among Asian individuals (17.2%) and greatest among non-Hispanic Black individuals (56.9%), with White (39.8%) and Hispanic individuals (43.7%) having rates in between.² In a meta-analysis of prospective studies that included 4 million people who were never smokers and had no chronic disease at baseline, age- and sex-adjusted mortality rates were studied over a median of 14 years of follow-up.³ Compared with those with a BMI of 20 to 25 kg/m², people with a BMI of 30 to 34.9 kg/m² or a BMI of 35 to 39.9 kg/m² had increased risks of death of 46% and 94%, respectively, demonstrating that obesity increases this risk.³

The increased risk of death associated with obesity is caused by obesity-related diseases that cause early mortality, including diabetes mellitus (DM), dyslipidemia, hypertension, coronary heart disease, heart failure, atrial fibrillation, stroke, and venous thromboembolic events.⁴ Obesity is also associated with an increased risk of many cancers, including cancer of the endometrium, kidney, esophagus, stomach, colon, rectum, gallbladder, pancreas, liver, and breast.⁵ With regard to gynecologic disease, obesity is associated with an increased risk of fibroids and heavy menstrual bleeding.⁶ For pregnant patients, obesity is associated with increased risks of⁷:

• miscarriage and stillbirth
• preeclampsia and gestational hypertension
• gestational diabetes
• severe maternal morbidity
• postterm pregnancy
• venous thromboembolism
• endometritis.

For obese patients, weight loss can normalize blood pressure, reduce the risk of cardiovascular events, decrease the risk of cancer, and cure type 2 DM.⁸

Bariatric surgery: The gold standard treatment for reliable and sustained weight loss

All patients with obesity should be counseled to reduce caloric intake and increase physical activity. Dietary counseling provided by a nutritionist may help reinforce advice given by a provider. However, lifestyle interventions are associated with modest weight loss (<5% of bodyweight; FIGURE).⁹ The gold standard treatment for reliable and sustained weight loss is bariatric surgery.

In the Swedish Obese Subjects study, involving 2,010 people, following bariatric surgery the mean decrease in bodyweight was 23% at 2 years, with a slow increase in weight thereafter, resulting in a sustained mean weight loss of 18% at 10 years.⁸ In this study, people in the diet and exercise control group had no change in bodyweight over 10 years of follow-up.⁸ Not all eligible obese patients want to undergo bariatric surgery because it is an arduous sequential process involving 6 months of intensive preoperative preparation, bariatric surgery, recovery, and intensive postoperative follow-up. The perioperative mortality rate is 0.03% to 0.2%.¹⁰ Following bariatric surgery, additional operations may be necessary for more than 10% of patients.¹⁰ With recent breakthroughs in the medication management of obesity, patients who do not want bariatric surgery can achieve reliable weight loss of greater than 10% of body weight with glucagon-like peptide -1 (GLP-1) agonists.

ILLUSTRATION: KIMBERLY MARTENS FOR OBG MANAGEMENT

GLP-1 agonist analogues: Practice-changing breakthrough in medication treatment

GLP-1, a 30 amino acid peptide, is produced by intestinal enteroendocrine cells and neurons in the medulla and hypothalamus.¹¹ GLP-1 reduces hunger cravings and causes satiety, reducing daily food intake.¹² GLP-1 also enhances the secretion of insulin, making GLP-1 agonists an effective treatment for type 2 DM. In humans and experimental animals, the administration of exogenous GLP-1 agonists decreases hunger cravings and causes satiety, reducing food intake, resulting in weight loss.¹² The synthetic GLP-1 agonists, liraglutide (Saxenda) and semaglutide (Wegovy) are approved by the US Food and Drug Administration (FDA) as anti-obesity medications.

Native GLP-1 has a short circulating half-life of approximately 2 minutes. The synthetic GLP-1 agonist medications liraglutide and semaglutide are modified to significantly increase their half-life. Liraglutide is a modified version of GLP-1 with a palmitic acid side chain and an amino acid spacer resulting in reduced degradation and a 15-hour half-life, necessitating daily administration. Semaglutide has a steric acid diacid at Lys26, a large synthetic spacer, a modification of amino acid 8 with the addition of α-aminobutyric acid and a 165-hour half-life, permitting weekly administration.¹³ For weight loss, liraglutide and semaglultide are administered by subcutaneous injection. Tirzepatide (Mounjaro) is a novel GLP-1 agonist. It is also a gastric inhibitory peptide, is FDA approved to treat type 2 DM, and is awaiting FDA approval as a weight loss medication.Tirzepatide causes substantial weight loss, similar to the effect of semaglutide.¹⁴

Semaglutide and weight loss

Semaglutide is approved by the FDA for chronic weight management as an adjunct to a reduced-calorie diet and increased physical activity in adults with a BMI ≥ 30 kg/m² or ≥ 27 kg/m² in the presence of a weight-related comorbidity. It is also FDA approved to treat type 2 DM.

In a weight loss trial, 1,961 overweight and obese patients with a mean BMI of 38 kg/m², were randomly assigned to semaglutide or placebo treatment for 68 weeks. All the participants were following a regimen that included a calorie-reduced diet and increased physical activity. The mean changes in body weight for the patients in the semaglutide and placebo treatment groups were -14.9% and -2.4%, respectively. The treatment difference was -12.4% (95% confidence interval [CI], -13.4% to -11.5%; P <.001). In this study, compared with placebo, semaglutide treatment resulted in a greater decrease in waist circumference, -5.3 in versus -1.6 in.¹⁵ A network meta-analysis of the efficacy of weight loss medicines indicates that semaglutide is the most effective medication currently FDA approved for weight loss, reliably producing substantial weight loss (FIGURE).⁹

In one randomized clinical trial, investigators directly compared the efficacy of semaglutide and liraglutide in achieving weight loss. In this trial, 338 patients were assigned randomly to treatment with semaglutide 2.4 mg weekly subcutaneous injection, liraglutide 3.0 mg daily subcutaneous injection, or placebo. All the participants were following a regimen that included a calorie-reduced diet and increased physical activity.¹⁶ After 68 weeks of treatment, the mean weight changes were -15.8%, -6.4%, and -1.9% in the semaglutide, liraglutide, and placebo groups, respectively. The difference between the semaglutide and liraglutide groups was -9.4% (95% CI, -12% to -6.8%; P <.001).¹⁶

Continue to: Semaglutide dose-escalation and contraindications...

For weight loss, the target dose of semaglutide is 2.4 mg once weekly subcutaneous injection achieved by sequential dose escalation. To give patients time to adjust to adverse effects caused by the medication, a standardized dose-escalation regimen is recommended. The FDA-approved escalation regimen for semaglutide treatment begins with a weekly subcutaneous dose of 0.25 mg for 4 weeks, followed by an increase in the weekly dosage every 4 weeks: 0.5 mg, 1.0 mg, 1.7 mg, and 2.4 mg.¹⁷ To support the dose-escalation process there are 5 unique autoinjectors that deliver the appropriate dose for the current step.

Semaglutide is contraindicated if the patient has an allergy to the medication or if there is a personal or family history of medullary thyroid cancer.¹⁷ In animal toxicology studies, semaglutide at clinically relevant dosing was associated with an increased risk of developing medullary thyroid cancer. Patients with a personal history of multiple endocrine neoplasia syndrome type 2, (medullary thyroid cancer, pheochromocytoma, and primary hyperparathyroidism) should not take semaglutide. Semaglutide may cause fetal harm and the FDA recommends discontinuing semaglutide at least 2 months before pregnancy.¹⁷ According to the FDA, the safety of semaglutide during breastfeeding has not been established. In Canada, breastfeeding is a contraindication to semaglutide treatment.¹⁸

Limitations of medication treatment of obesity

There are important limitations to semaglutide treatment of obesity, including:

• weight gain after stopping treatment
• limited medical insurance supportfor an expensive medication treatment
• bothersome adverse effects.

Weight gain posttreatment. After stopping medication treatment of obesity, weight gain occurs in most patients. However, patients may remain below baseline weight for a long time after stopping medication therapy. In one trial of 803 patients, after 20 weeks of semaglutide treatment (16-week dose-escalation phase, followed by 4 weeks on a weekly dose of 2.4 mg), the participants were randomized to 48 additional weeks of semaglutide or placebo.¹⁹ All the participants were following a regimen that included a calorie-reduced diet and increased physical activity. At the initial 20 weeks of treatment time point the mean weight change was -10.6%. Over the following 48 weeks, the patients treated with semaglutidehad an additional mean weight change of -7.9%, while the mean weight change for the placebo group was +6.9%.

Medical insurance coverage. A major barrier to semaglutide treatment of obesity is the medication’s cost. At the website GoodRx (https://www.goodrx.com/), the estimated price for a 1-month supply of semaglutide (Wegovy) is $1,350.²⁰ By contrast, a 1-month supply of phentermine-topiramate (Qsymia) is approximately $205. Currently, many medical insurance plans do not cover the cost of semaglutide treatment for weight loss. Patent protection for liraglutide may expire in the next few years, permitting the marketing of a lower-cost generic formulation, increasing the availability of the medication. However, as noted above, compared with liraglutide, semaglutide treatment results in much greater weight loss.

The most common adverse effects associated with semaglutide treatment are nausea, vomiting, diarrhea, and constipation. In one randomized clinical trial involving 1,961 patients, the frequency of adverse effects reported by patients taking semaglutide incrementally above the frequency of the same adverse effect reported by patients on placebo was: nausea (27%), vomiting (18%), diarrhea (16%), constipation (14%), dyspepsia (7%), and abdominal pain (5%).¹⁵ In this study, treatment was discontinued due to adverse effects in 7% and 3% of the patients in the semaglutide and placebo groups, respectively. Experts believe that adverse effects can be minimized by increasing the dose slowly and decreasing the dose if adverse effects are bothersome to the patient.

Measuring the benefits of semaglutide weight loss

Overweight and obesity are prevalent problems with many adverse consequences, including an increased risk of death. In population studies, weight loss following bariatric surgery is associated with a substantial reduction in mortality, cancer, and heart disease compared with conventional therapy.²¹ Over the next few years, the effect of semaglutide-induced weight loss on the rate of cancer and heart disease should become clear. If semaglutide treatment of obesity is associated with a reduction in cancer and heart disease, it would be a truly breakthrough medication. ●