Tara Haelle

Members of the LGBTQ community who give birth appear to have a greater risk of hypertensive disorders of pregnancy and postpartum hemorrhage, according to new research presented at the annual meeting sponsored by the Society for Maternal-Fetal Medicine.

“Our study found that birthing patients in likely sexual and gender minority partnerships experienced disparities in clinical outcomes,” Stephanie Leonard, PhD, an epidemiology and biostatistics instructor at the Stanford (Calif.) University division of maternal-fetal medicine and obstetrics, told attendees at the meeting. The disparities are likely because of various social determinants and possibly higher use of assisted reproductive technology (ART). The findings establish “how these are significant disparities that have been largely overlooked and set the groundwork for doing further research on maybe ways that we can improve the inclusivity of obstetric care.”

Jenny Mei, MD, a maternal-fetal medicine fellow at the University of California, Los Angeles, who attended the presentation but was not involved in the research, said the findings were “overall unfortunate but not surprising given the existing studies looking at LGBTQ patients and their poorer health outcomes, largely due to lack of access to health care and discrimination in the health care setting.”

Dr. Leonard described the societal, interpersonal, and individual factors that can contribute to health disparities among gender and sexual minority patients.

“At the societal level, there are expectations of what it means to be pregnant, to give birth, and to be a parent. At the community level, there’s the clinical care environment, and at the interpersonal level, there’s an obstetrician’s relationship with the patient,” Dr. Leonard said. “At the individual level, most notably is minority stress, the biological effects of the chronic experience of discrimination.”

It has historically been difficult to collect data on this patient population, but a change in the design of the California birth certificate made it possible to gather more data than previously possible. The updated California birth certificate, issued in 2016, allows the parent not giving birth to check off whether they are the child’s mother, father, parent, or “not specified” instead of defaulting to “father.” In addition, the parent giving birth can select mother, father, parent or not specified instead of being “mother” by default.

The researchers classified sexual and gender minority (SGM) partnerships as those in which the parent giving birth was identified as the father and those where both parents were identified as mothers. Non-SGM minority partnerships were those in which the birthing parent was identified as the mother and the nonbirthing parent was identified as the father.

The population-based cohort study included data from all live birth hospitalizations from 2016-2019 in California, whose annual births represent one in eight babies born each year in the United States. The population of SGM patients different significantly from the non-SGM population in nearly every demographic and clinical factor except rates of pre-existing diabetes. For example, 42% of the SGM birthing patients were age 35 or older, compared with 23% of the non-SGM patients.

SGM patients were more likely to be born in the United States, were more likely to be White, and were less likely to be Asian or Hispanic. SGM patients had higher education levels and were more likely to have private insurance. They were also more likely to be nulliparous and have chronic hypertension. Average body mass index for SGM patients was 33 kg/m², compared with 30 for non-SGM patients. SGM patients were also much more likely to have multifetal gestation: 7.1% of SGM patients versus 1.5% of non-SGM patients.

In terms of clinical outcomes, 14% of SGM patients had hypertensive disorders of pregnancy, compared with 8% of non-SGM patients. Before adjustment for potential confounders, SGM patients were also twice as likely to have postpartum hemorrhage (8% vs. 4% in non-SGM patients) and postterm birth at 42-44 weeks (0.6% vs 0.3% in non-SGM patients).

“Having increased postterm birth is a matter of declining induction of labor, as it is recommended to have an induction by 41 weeks of gestation in general,” Dr. Mei said in an interview. “It is also possible this patient cohort faces more barriers in access to care and possible discrimination as sexual/gender minority patients.”

Rates of severe preeclampsia, induction of labor, cesarean delivery, preterm birth, low birth weight, and a low Apgar score were also higher among SGM patients, but these associations were no longer significant after adjustment for age, education, payment method, parity, prepregnancy weight, comorbidities, and multifetal gestation. The difference in hypertensive disorders of pregnancy, postpartum hemorrhage, and postterm birth remained statistically significant after adjustment.

Past research has shown that only about a third of cisgender female same-sex marriages used ART, so the disparities cannot be completely explained by ART use, Dr. Leonard said.

“I think the main drivers are structural disparities,” Dr. Leonard said. “Every obstetric clinic is focused in a way that’s about mother-father, and many people who don’t feel like they fit into that paradigm feel excluded and disengage with health care.”

Elliott Main, MD, a clinical professor of obstetrics and gynecology at Stanford University and coauthor of the study noted that discrimination and stigma likely play a substantial role in the disparities.

“Sexual and/or gender minority people face this discrimination at structural and interpersonal levels on a regular basis, which can lead to chronic stress and its harmful physical effects as well as lower-quality health care,” Dr. Main said in an interview.

Another coauthor, Juno Obedin-Maliver, MD, an assistant professor of obstetrics and gynecology at Stanford, emphasized how much room for improvement exists in care for SGM obstetric patients.

“We hope that this study brings needed attention to the disparities in perinatal health experienced by sexual and/or gender minority people,” Dr. Obedin-Maliver said. “There is much we can do to better understand the family building goals of sexual and/or gender minority people and help those to be achieved with healthy outcomes for parents and their children.”

One limitation of the study is that it’s possible to misclassify individuals using the birth certificate data, and not everyone may be comfortable selecting the box that accurately represents their identity, particularly if they aren’t “out” or fear discrimination or stigma, so the population may underrepresent the actual numbers of sexual and gender minority individuals giving birth. Dr. Mei added that it would be helpful to see data on neonatal ICU admissions and use of ART.

It’s difficult to say how generalizable the findings are, Dr. Mei said. “It is possible the findings would be more exaggerated in the rest of the country outside of California, if we assume there is potentially lower health access and more stigma.” The fact that California offers different gender options for the birthing and nonbirthing parent is, by itself, an indication of a potentially more accepting social environment than might be found in other states.

”The take-home message is that this patient population is higher risk, likely partially due to baseline increased risk factors, such as older maternal age and likely use of ART, and partially due to possible lack of health access and stigma,” Dr. Mei said. “Health care providers should be notably cognizant of these increased risks, particularly in the psychosocial context and make efforts to reduce those burdens as much as possible.”

The research was funded by the Stanford Maternal and Child Health Research Institute. Dr. Obedin-Maliver has consulted for Sage Therapeutics, Ibis Reproductive Health, and Hims. Dr. Mei and the other authors had no disclosures.

Members of the LGBTQ community who give birth appear to have a greater risk of hypertensive disorders of pregnancy and postpartum hemorrhage, according to new research presented at the annual meeting sponsored by the Society for Maternal-Fetal Medicine.

“Our study found that birthing patients in likely sexual and gender minority partnerships experienced disparities in clinical outcomes,” Stephanie Leonard, PhD, an epidemiology and biostatistics instructor at the Stanford (Calif.) University division of maternal-fetal medicine and obstetrics, told attendees at the meeting. The disparities are likely because of various social determinants and possibly higher use of assisted reproductive technology (ART). The findings establish “how these are significant disparities that have been largely overlooked and set the groundwork for doing further research on maybe ways that we can improve the inclusivity of obstetric care.”

Jenny Mei, MD, a maternal-fetal medicine fellow at the University of California, Los Angeles, who attended the presentation but was not involved in the research, said the findings were “overall unfortunate but not surprising given the existing studies looking at LGBTQ patients and their poorer health outcomes, largely due to lack of access to health care and discrimination in the health care setting.”

Dr. Leonard described the societal, interpersonal, and individual factors that can contribute to health disparities among gender and sexual minority patients.

“At the societal level, there are expectations of what it means to be pregnant, to give birth, and to be a parent. At the community level, there’s the clinical care environment, and at the interpersonal level, there’s an obstetrician’s relationship with the patient,” Dr. Leonard said. “At the individual level, most notably is minority stress, the biological effects of the chronic experience of discrimination.”

It has historically been difficult to collect data on this patient population, but a change in the design of the California birth certificate made it possible to gather more data than previously possible. The updated California birth certificate, issued in 2016, allows the parent not giving birth to check off whether they are the child’s mother, father, parent, or “not specified” instead of defaulting to “father.” In addition, the parent giving birth can select mother, father, parent or not specified instead of being “mother” by default.

The researchers classified sexual and gender minority (SGM) partnerships as those in which the parent giving birth was identified as the father and those where both parents were identified as mothers. Non-SGM minority partnerships were those in which the birthing parent was identified as the mother and the nonbirthing parent was identified as the father.

The population-based cohort study included data from all live birth hospitalizations from 2016-2019 in California, whose annual births represent one in eight babies born each year in the United States. The population of SGM patients different significantly from the non-SGM population in nearly every demographic and clinical factor except rates of pre-existing diabetes. For example, 42% of the SGM birthing patients were age 35 or older, compared with 23% of the non-SGM patients.

SGM patients were more likely to be born in the United States, were more likely to be White, and were less likely to be Asian or Hispanic. SGM patients had higher education levels and were more likely to have private insurance. They were also more likely to be nulliparous and have chronic hypertension. Average body mass index for SGM patients was 33 kg/m², compared with 30 for non-SGM patients. SGM patients were also much more likely to have multifetal gestation: 7.1% of SGM patients versus 1.5% of non-SGM patients.

In terms of clinical outcomes, 14% of SGM patients had hypertensive disorders of pregnancy, compared with 8% of non-SGM patients. Before adjustment for potential confounders, SGM patients were also twice as likely to have postpartum hemorrhage (8% vs. 4% in non-SGM patients) and postterm birth at 42-44 weeks (0.6% vs 0.3% in non-SGM patients).

“Having increased postterm birth is a matter of declining induction of labor, as it is recommended to have an induction by 41 weeks of gestation in general,” Dr. Mei said in an interview. “It is also possible this patient cohort faces more barriers in access to care and possible discrimination as sexual/gender minority patients.”

Rates of severe preeclampsia, induction of labor, cesarean delivery, preterm birth, low birth weight, and a low Apgar score were also higher among SGM patients, but these associations were no longer significant after adjustment for age, education, payment method, parity, prepregnancy weight, comorbidities, and multifetal gestation. The difference in hypertensive disorders of pregnancy, postpartum hemorrhage, and postterm birth remained statistically significant after adjustment.

Past research has shown that only about a third of cisgender female same-sex marriages used ART, so the disparities cannot be completely explained by ART use, Dr. Leonard said.

“I think the main drivers are structural disparities,” Dr. Leonard said. “Every obstetric clinic is focused in a way that’s about mother-father, and many people who don’t feel like they fit into that paradigm feel excluded and disengage with health care.”

Elliott Main, MD, a clinical professor of obstetrics and gynecology at Stanford University and coauthor of the study noted that discrimination and stigma likely play a substantial role in the disparities.

“Sexual and/or gender minority people face this discrimination at structural and interpersonal levels on a regular basis, which can lead to chronic stress and its harmful physical effects as well as lower-quality health care,” Dr. Main said in an interview.

Another coauthor, Juno Obedin-Maliver, MD, an assistant professor of obstetrics and gynecology at Stanford, emphasized how much room for improvement exists in care for SGM obstetric patients.

“We hope that this study brings needed attention to the disparities in perinatal health experienced by sexual and/or gender minority people,” Dr. Obedin-Maliver said. “There is much we can do to better understand the family building goals of sexual and/or gender minority people and help those to be achieved with healthy outcomes for parents and their children.”

One limitation of the study is that it’s possible to misclassify individuals using the birth certificate data, and not everyone may be comfortable selecting the box that accurately represents their identity, particularly if they aren’t “out” or fear discrimination or stigma, so the population may underrepresent the actual numbers of sexual and gender minority individuals giving birth. Dr. Mei added that it would be helpful to see data on neonatal ICU admissions and use of ART.

It’s difficult to say how generalizable the findings are, Dr. Mei said. “It is possible the findings would be more exaggerated in the rest of the country outside of California, if we assume there is potentially lower health access and more stigma.” The fact that California offers different gender options for the birthing and nonbirthing parent is, by itself, an indication of a potentially more accepting social environment than might be found in other states.

”The take-home message is that this patient population is higher risk, likely partially due to baseline increased risk factors, such as older maternal age and likely use of ART, and partially due to possible lack of health access and stigma,” Dr. Mei said. “Health care providers should be notably cognizant of these increased risks, particularly in the psychosocial context and make efforts to reduce those burdens as much as possible.”

The research was funded by the Stanford Maternal and Child Health Research Institute. Dr. Obedin-Maliver has consulted for Sage Therapeutics, Ibis Reproductive Health, and Hims. Dr. Mei and the other authors had no disclosures.

Members of the LGBTQ community who give birth appear to have a greater risk of hypertensive disorders of pregnancy and postpartum hemorrhage, according to new research presented at the annual meeting sponsored by the Society for Maternal-Fetal Medicine.

“Our study found that birthing patients in likely sexual and gender minority partnerships experienced disparities in clinical outcomes,” Stephanie Leonard, PhD, an epidemiology and biostatistics instructor at the Stanford (Calif.) University division of maternal-fetal medicine and obstetrics, told attendees at the meeting. The disparities are likely because of various social determinants and possibly higher use of assisted reproductive technology (ART). The findings establish “how these are significant disparities that have been largely overlooked and set the groundwork for doing further research on maybe ways that we can improve the inclusivity of obstetric care.”

Jenny Mei, MD, a maternal-fetal medicine fellow at the University of California, Los Angeles, who attended the presentation but was not involved in the research, said the findings were “overall unfortunate but not surprising given the existing studies looking at LGBTQ patients and their poorer health outcomes, largely due to lack of access to health care and discrimination in the health care setting.”

Dr. Leonard described the societal, interpersonal, and individual factors that can contribute to health disparities among gender and sexual minority patients.

“At the societal level, there are expectations of what it means to be pregnant, to give birth, and to be a parent. At the community level, there’s the clinical care environment, and at the interpersonal level, there’s an obstetrician’s relationship with the patient,” Dr. Leonard said. “At the individual level, most notably is minority stress, the biological effects of the chronic experience of discrimination.”

It has historically been difficult to collect data on this patient population, but a change in the design of the California birth certificate made it possible to gather more data than previously possible. The updated California birth certificate, issued in 2016, allows the parent not giving birth to check off whether they are the child’s mother, father, parent, or “not specified” instead of defaulting to “father.” In addition, the parent giving birth can select mother, father, parent or not specified instead of being “mother” by default.

The researchers classified sexual and gender minority (SGM) partnerships as those in which the parent giving birth was identified as the father and those where both parents were identified as mothers. Non-SGM minority partnerships were those in which the birthing parent was identified as the mother and the nonbirthing parent was identified as the father.

The population-based cohort study included data from all live birth hospitalizations from 2016-2019 in California, whose annual births represent one in eight babies born each year in the United States. The population of SGM patients different significantly from the non-SGM population in nearly every demographic and clinical factor except rates of pre-existing diabetes. For example, 42% of the SGM birthing patients were age 35 or older, compared with 23% of the non-SGM patients.

SGM patients were more likely to be born in the United States, were more likely to be White, and were less likely to be Asian or Hispanic. SGM patients had higher education levels and were more likely to have private insurance. They were also more likely to be nulliparous and have chronic hypertension. Average body mass index for SGM patients was 33 kg/m², compared with 30 for non-SGM patients. SGM patients were also much more likely to have multifetal gestation: 7.1% of SGM patients versus 1.5% of non-SGM patients.

In terms of clinical outcomes, 14% of SGM patients had hypertensive disorders of pregnancy, compared with 8% of non-SGM patients. Before adjustment for potential confounders, SGM patients were also twice as likely to have postpartum hemorrhage (8% vs. 4% in non-SGM patients) and postterm birth at 42-44 weeks (0.6% vs 0.3% in non-SGM patients).

“Having increased postterm birth is a matter of declining induction of labor, as it is recommended to have an induction by 41 weeks of gestation in general,” Dr. Mei said in an interview. “It is also possible this patient cohort faces more barriers in access to care and possible discrimination as sexual/gender minority patients.”

Rates of severe preeclampsia, induction of labor, cesarean delivery, preterm birth, low birth weight, and a low Apgar score were also higher among SGM patients, but these associations were no longer significant after adjustment for age, education, payment method, parity, prepregnancy weight, comorbidities, and multifetal gestation. The difference in hypertensive disorders of pregnancy, postpartum hemorrhage, and postterm birth remained statistically significant after adjustment.

Past research has shown that only about a third of cisgender female same-sex marriages used ART, so the disparities cannot be completely explained by ART use, Dr. Leonard said.

“I think the main drivers are structural disparities,” Dr. Leonard said. “Every obstetric clinic is focused in a way that’s about mother-father, and many people who don’t feel like they fit into that paradigm feel excluded and disengage with health care.”

Elliott Main, MD, a clinical professor of obstetrics and gynecology at Stanford University and coauthor of the study noted that discrimination and stigma likely play a substantial role in the disparities.

“Sexual and/or gender minority people face this discrimination at structural and interpersonal levels on a regular basis, which can lead to chronic stress and its harmful physical effects as well as lower-quality health care,” Dr. Main said in an interview.

Another coauthor, Juno Obedin-Maliver, MD, an assistant professor of obstetrics and gynecology at Stanford, emphasized how much room for improvement exists in care for SGM obstetric patients.

“We hope that this study brings needed attention to the disparities in perinatal health experienced by sexual and/or gender minority people,” Dr. Obedin-Maliver said. “There is much we can do to better understand the family building goals of sexual and/or gender minority people and help those to be achieved with healthy outcomes for parents and their children.”

One limitation of the study is that it’s possible to misclassify individuals using the birth certificate data, and not everyone may be comfortable selecting the box that accurately represents their identity, particularly if they aren’t “out” or fear discrimination or stigma, so the population may underrepresent the actual numbers of sexual and gender minority individuals giving birth. Dr. Mei added that it would be helpful to see data on neonatal ICU admissions and use of ART.

It’s difficult to say how generalizable the findings are, Dr. Mei said. “It is possible the findings would be more exaggerated in the rest of the country outside of California, if we assume there is potentially lower health access and more stigma.” The fact that California offers different gender options for the birthing and nonbirthing parent is, by itself, an indication of a potentially more accepting social environment than might be found in other states.

”The take-home message is that this patient population is higher risk, likely partially due to baseline increased risk factors, such as older maternal age and likely use of ART, and partially due to possible lack of health access and stigma,” Dr. Mei said. “Health care providers should be notably cognizant of these increased risks, particularly in the psychosocial context and make efforts to reduce those burdens as much as possible.”

The research was funded by the Stanford Maternal and Child Health Research Institute. Dr. Obedin-Maliver has consulted for Sage Therapeutics, Ibis Reproductive Health, and Hims. Dr. Mei and the other authors had no disclosures.

The potential effectiveness of using vaginal progesterone to prevent preterm birth in two different populations was the focus of a pair of studies with mixed results at the annual meeting sponsored by the Society for Maternal-Fetal Medicine on Feb. 3. One study found no benefit from vaginal progesterone in those with first trimester bleeding, while the other, in a head-to-head comparison with 17-alpha-hydroxyprogesterone caproate (17-OHPC), found vaginal progesterone performs similarly to 17-OHPC in singleton pregnancies with a history of preterm birth.

While the first study does not suggest any changes in clinical practice, the second one suggests that vaginal progesterone is an alternative to 17-OHPC, as the American College of Obstetricians and Gynecologists currently recommends. SMFM currently only includes 17-OHPC in its guidelines.

“In otherwise low-risk pregnancies with first trimester bleeding, progesterone should not be prescribed for the prevention of miscarriage or prematurity,” Haim A. Abenhaim, MD, MPH, of the Jewish General Hospital at McGill University, Montreal, told attendees in his presentation.

”Publishing the negative result is so important because this helps the overall body of literature reduce the amount of publication bias that exists in the literature,” Michael Richley, MD, an ob.gyn. and maternal-fetal medicine fellow at the University of California, Los Angeles, said in an interview. Dr. Richley was not involved in the research but attended the presentation.
 

Vaginal progesterone for first trimester bleeding

Most preterm birth occurs in pregnancies with no identifiable risk factors, but first-trimester bleeding may indicate subchorionic hemorrhage from placental detachment, which can increase the risk of preterm birth. Other risk factors where progesterone has previously shown effectiveness in reducing preterm birth risk include short cervix and a history of prior preterm birth.

The first study (PREEMPT) was a double-blind, randomized controlled trial conducted at six Canadian hospitals with 533 women. The participants all experienced bleeding within the first 14 weeks of pregnancy and a documented subchorionic hemorrhage. The trial excluded those who already required progesterone, had contraindications to progesterone or had an alternate cause of bleeding.

The intervention group included 264 women randomly assigned to use 200 mg of micronized progesterone administered with a vaginal suppository at bedtime, while the placebo group included 269 women who used a vaginal suppository with no medication, both administered until 34 weeks of pregnancy. The groups were not significantly different in age, race, or former pregnancies, live births, and miscarriages. They were also similar in clinical characteristics of bleeding and subchorionic hemorrhage.

The proportion of term births was similar between the progesterone (74.6%) and placebo (70.6%) groups (P =.3), as was the proportion of preterm births (10.2% progesterone vs. 12.3% placebo, P =.46). There were also no significant differences in the secondary outcomes of cramping, hospital admission, bed rest, or preventive measures, including pessary, cerclage, antibiotics, magnesium, and nifedipine. Newborns across both groups were statistically similar in average birth weight and distribution of birth weights and in incidence of neonatal ICU admission or respiratory distress syndrome. Adverse events were similar across both groups.

”The results are not surprising as several studies in the past have shown similar lack of efficacy,” Dr. said. “The pathophysiology of subchorionic hematoma is different from the multifactorial etiologies of spontaneous preterm birth, and given our lack of clear understanding of the actions of progesterone, the lack of efficacy in this subgroup with subchorionic hematoma is not surprising.”

Dr. Richley did note that having a low-risk population to start with may have affected the findings, which might be different in a high-risk population.

“I don’t believe this will change anything within clinical practice. At this time, progesterone is not used in any form in the setting of first trimester threatened abortion by maternal-fetal medicine specialists,” Dr. Richley said. “There may be other subgroups of clinicians who do prescribe progesterone in this setting, and these data should further encourage them to move away from this practice.”

Dr. Abenhaim noted a couple unexpected issues that occurred during the course of the study, such as underreporting of subchorionic hemorrhage with radiologic confirmation that resulted in a smaller population and a change in protocol to include patients with no identifiable secondary source of bleeding. The pandemic also halted enrollment, and the investigators halted the trial when recruitment could have continued since interim analysis showed no likely benefit.

Though first trimester bleeding is associated with a 25%-30% increased risk of miscarriage or preterm birth, the findings showed that progesterone did not prevent miscarriage or prematurity, or increase the live birth rate, in low-risk patients with first trimester bleeding.
 

Vaginal progesterone vs. 17-OHPC

Although a 2017 meta-analysis had found vaginal progesterone to be superior to 17-OHPC in preventing preterm birth, few studies were available, and they had wide confidence intervals. This open-label randomized controlled trial took place at five U.S. sites and included participants who had a singleton pregnancy less than 24 weeks along and a history of singleton preterm birth between 16 and 37 weeks. The trials excluded those with placenta previa or accreta, preterm labor, preterm premature rupture of the membranes, clinical chorioamnionitis, or a major fetal anomaly or chromosomal disorder.

Among 205 women initially randomized, 94 in each group completed the trial, either inserting 200 mg of micronized progesterone daily with a vaginal suppository or receiving 250 mg of weekly intramuscular injections of 17-OHPC from 16 to 36 weeks’ gestation. The only significant difference between the groups in demographics or clinical features was that the vaginal progesterone group had a higher proportion of multiple past preterm births (33%) compared with the 17-OHPC group (17%). Cervical length and use of cerclage were also similar between the groups.

Though 30.9% of the vaginal progesterone group delivered preterm before 37 weeks, compared with 38.3% in the 17-OHPC group, the difference was not significant (P =.28). There was a borderline statistical difference between gestational age at delivery: 37.4 weeks in the vaginal progesterone group versus 36.3 weeks in the 17-OHPC group (P =.047). Neonatal outcomes were clinically similar between the two groups. Therapy initiation did slightly differ between the groups, with an average start 1 gestational week earlier in the vaginal progesterone group (16.9 vs. 17.8, P =.001) and a higher proportion of patients in the 17-OHPC group initiating therapy after 20 weeks (16.5% vs. 2.2%, P =.001). Adherence was otherwise similar between the groups, and the groups reported similar rates and types of side effects.

The trial did not meet the primary endpoint of vaginal progesterone reducing risk of recurrent preterm birth by 50%, compared with 17-OHPC, but it may increase latency to delivery, Rupsa C. Boelig, MD, of Thomas Jefferson University, Philadelphia, told attendees. Though this was the largest trial to compare vaginal progesterone with 17-OHPC for preventing preterm birth, it was underpowered to detect a difference in efficacy, to conduct subgroup analyses, and to assess secondary outcomes, Dr. Boelig noted. “Baseline difference in preterm birth risk may affect apparent relative efficacy of vaginal progesterone.”

Nevertheless, the “totality of evidence appears to be greater for vaginal progesterone,” Dr. Boelig said, making vaginal progesterone an acceptable alternative to 17-OHPC. ACOG recommendations currently include offering either, but SMFM recommendations only mention 17-OHPC.

It’s worth noting, however, that the future of 17-OHPC, a synthetic compound, compared with naturally occurring micronized progesterone, continues to be uncertain following a 2020 study that found no evidence of its efficacy, leading the Food and Drug Administration to withdraw its approval for prevention of preterm birth. ”These findings are important especially in light of the controversy surrounding 17-OHP,” Jenny Mei, MD, a maternal-fetal medicine fellow at UCLA, said in an interview after attending the presentation. “It is also sometimes difficult for patients to commit to weekly 17-OHPC injections, which requires time and many doctors visits, as compared to vaginal progesterone, which patients can administer at home.” Since this study does not have a placebo group, “it does not address the question of the overall efficacy of either medication compared to a control,” Dr. Mei said. ”It is also a somewhat small patient population so the results may change with a larger population. The authors conclude it is worth readdressing the use of vaginal progesterone for these patients.”

Herman L. Hedriana, MD, professor and director of the division of maternal-fetal medicine and the maternal-fetal medicine fellowship program at the University of California, Davis, also pointed out notable differences between the two compounds.

“One has to remember that the formulation and mechanism of action are very different between 17-OHPC and the vaginal application of micronized progesterone. We do not have enough data to say one is superior versus the other,” said Dr. Hedriana, who was not involved in the research. “With 17-OHPC, the mechanism of action appears to be influenced by how the drug is metabolized based on race and ethnicity makeup, and may be influence by epigenetics,” while the mechanism for vaginal progesterone is probably local “given it is applied directly next to the cervix; hence, the results are it is effective in short cervices.” But those differing mechanisms don’t change the clinical significance of the findings. “One can use vaginal progesterone or 17-OHPC based on patient preference and availability,” Dr. Hedriana said.

The researchers of both studies reported no personal financial or industry disclosures, though Dr. Boelig disclosed that she had taken 17-OHPC and had cerclages during both her pregnancies, which resulted in healthy children today. The PREEMPT trial was funded by the Canadian Institutes of Health Research. The head-to-head trial was funded by the National Institute of Child Health and Development, the March of Dimes, the EW Thrasher Foundation, the PhRMA Foundation, and Covis Pharma, who manufactures the 17-OHPC drug Makena.

This story was updated on 2/8/2022.

The potential effectiveness of using vaginal progesterone to prevent preterm birth in two different populations was the focus of a pair of studies with mixed results at the annual meeting sponsored by the Society for Maternal-Fetal Medicine on Feb. 3. One study found no benefit from vaginal progesterone in those with first trimester bleeding, while the other, in a head-to-head comparison with 17-alpha-hydroxyprogesterone caproate (17-OHPC), found vaginal progesterone performs similarly to 17-OHPC in singleton pregnancies with a history of preterm birth.

While the first study does not suggest any changes in clinical practice, the second one suggests that vaginal progesterone is an alternative to 17-OHPC, as the American College of Obstetricians and Gynecologists currently recommends. SMFM currently only includes 17-OHPC in its guidelines.

“In otherwise low-risk pregnancies with first trimester bleeding, progesterone should not be prescribed for the prevention of miscarriage or prematurity,” Haim A. Abenhaim, MD, MPH, of the Jewish General Hospital at McGill University, Montreal, told attendees in his presentation.

”Publishing the negative result is so important because this helps the overall body of literature reduce the amount of publication bias that exists in the literature,” Michael Richley, MD, an ob.gyn. and maternal-fetal medicine fellow at the University of California, Los Angeles, said in an interview. Dr. Richley was not involved in the research but attended the presentation.
 

Vaginal progesterone for first trimester bleeding

Most preterm birth occurs in pregnancies with no identifiable risk factors, but first-trimester bleeding may indicate subchorionic hemorrhage from placental detachment, which can increase the risk of preterm birth. Other risk factors where progesterone has previously shown effectiveness in reducing preterm birth risk include short cervix and a history of prior preterm birth.

The first study (PREEMPT) was a double-blind, randomized controlled trial conducted at six Canadian hospitals with 533 women. The participants all experienced bleeding within the first 14 weeks of pregnancy and a documented subchorionic hemorrhage. The trial excluded those who already required progesterone, had contraindications to progesterone or had an alternate cause of bleeding.

The intervention group included 264 women randomly assigned to use 200 mg of micronized progesterone administered with a vaginal suppository at bedtime, while the placebo group included 269 women who used a vaginal suppository with no medication, both administered until 34 weeks of pregnancy. The groups were not significantly different in age, race, or former pregnancies, live births, and miscarriages. They were also similar in clinical characteristics of bleeding and subchorionic hemorrhage.

The proportion of term births was similar between the progesterone (74.6%) and placebo (70.6%) groups (P =.3), as was the proportion of preterm births (10.2% progesterone vs. 12.3% placebo, P =.46). There were also no significant differences in the secondary outcomes of cramping, hospital admission, bed rest, or preventive measures, including pessary, cerclage, antibiotics, magnesium, and nifedipine. Newborns across both groups were statistically similar in average birth weight and distribution of birth weights and in incidence of neonatal ICU admission or respiratory distress syndrome. Adverse events were similar across both groups.

”The results are not surprising as several studies in the past have shown similar lack of efficacy,” Dr. said. “The pathophysiology of subchorionic hematoma is different from the multifactorial etiologies of spontaneous preterm birth, and given our lack of clear understanding of the actions of progesterone, the lack of efficacy in this subgroup with subchorionic hematoma is not surprising.”

Dr. Richley did note that having a low-risk population to start with may have affected the findings, which might be different in a high-risk population.

“I don’t believe this will change anything within clinical practice. At this time, progesterone is not used in any form in the setting of first trimester threatened abortion by maternal-fetal medicine specialists,” Dr. Richley said. “There may be other subgroups of clinicians who do prescribe progesterone in this setting, and these data should further encourage them to move away from this practice.”

Dr. Abenhaim noted a couple unexpected issues that occurred during the course of the study, such as underreporting of subchorionic hemorrhage with radiologic confirmation that resulted in a smaller population and a change in protocol to include patients with no identifiable secondary source of bleeding. The pandemic also halted enrollment, and the investigators halted the trial when recruitment could have continued since interim analysis showed no likely benefit.

Though first trimester bleeding is associated with a 25%-30% increased risk of miscarriage or preterm birth, the findings showed that progesterone did not prevent miscarriage or prematurity, or increase the live birth rate, in low-risk patients with first trimester bleeding.
 

Vaginal progesterone vs. 17-OHPC

Although a 2017 meta-analysis had found vaginal progesterone to be superior to 17-OHPC in preventing preterm birth, few studies were available, and they had wide confidence intervals. This open-label randomized controlled trial took place at five U.S. sites and included participants who had a singleton pregnancy less than 24 weeks along and a history of singleton preterm birth between 16 and 37 weeks. The trials excluded those with placenta previa or accreta, preterm labor, preterm premature rupture of the membranes, clinical chorioamnionitis, or a major fetal anomaly or chromosomal disorder.

Among 205 women initially randomized, 94 in each group completed the trial, either inserting 200 mg of micronized progesterone daily with a vaginal suppository or receiving 250 mg of weekly intramuscular injections of 17-OHPC from 16 to 36 weeks’ gestation. The only significant difference between the groups in demographics or clinical features was that the vaginal progesterone group had a higher proportion of multiple past preterm births (33%) compared with the 17-OHPC group (17%). Cervical length and use of cerclage were also similar between the groups.

Though 30.9% of the vaginal progesterone group delivered preterm before 37 weeks, compared with 38.3% in the 17-OHPC group, the difference was not significant (P =.28). There was a borderline statistical difference between gestational age at delivery: 37.4 weeks in the vaginal progesterone group versus 36.3 weeks in the 17-OHPC group (P =.047). Neonatal outcomes were clinically similar between the two groups. Therapy initiation did slightly differ between the groups, with an average start 1 gestational week earlier in the vaginal progesterone group (16.9 vs. 17.8, P =.001) and a higher proportion of patients in the 17-OHPC group initiating therapy after 20 weeks (16.5% vs. 2.2%, P =.001). Adherence was otherwise similar between the groups, and the groups reported similar rates and types of side effects.

The trial did not meet the primary endpoint of vaginal progesterone reducing risk of recurrent preterm birth by 50%, compared with 17-OHPC, but it may increase latency to delivery, Rupsa C. Boelig, MD, of Thomas Jefferson University, Philadelphia, told attendees. Though this was the largest trial to compare vaginal progesterone with 17-OHPC for preventing preterm birth, it was underpowered to detect a difference in efficacy, to conduct subgroup analyses, and to assess secondary outcomes, Dr. Boelig noted. “Baseline difference in preterm birth risk may affect apparent relative efficacy of vaginal progesterone.”

Nevertheless, the “totality of evidence appears to be greater for vaginal progesterone,” Dr. Boelig said, making vaginal progesterone an acceptable alternative to 17-OHPC. ACOG recommendations currently include offering either, but SMFM recommendations only mention 17-OHPC.

It’s worth noting, however, that the future of 17-OHPC, a synthetic compound, compared with naturally occurring micronized progesterone, continues to be uncertain following a 2020 study that found no evidence of its efficacy, leading the Food and Drug Administration to withdraw its approval for prevention of preterm birth. ”These findings are important especially in light of the controversy surrounding 17-OHP,” Jenny Mei, MD, a maternal-fetal medicine fellow at UCLA, said in an interview after attending the presentation. “It is also sometimes difficult for patients to commit to weekly 17-OHPC injections, which requires time and many doctors visits, as compared to vaginal progesterone, which patients can administer at home.” Since this study does not have a placebo group, “it does not address the question of the overall efficacy of either medication compared to a control,” Dr. Mei said. ”It is also a somewhat small patient population so the results may change with a larger population. The authors conclude it is worth readdressing the use of vaginal progesterone for these patients.”

Herman L. Hedriana, MD, professor and director of the division of maternal-fetal medicine and the maternal-fetal medicine fellowship program at the University of California, Davis, also pointed out notable differences between the two compounds.

“One has to remember that the formulation and mechanism of action are very different between 17-OHPC and the vaginal application of micronized progesterone. We do not have enough data to say one is superior versus the other,” said Dr. Hedriana, who was not involved in the research. “With 17-OHPC, the mechanism of action appears to be influenced by how the drug is metabolized based on race and ethnicity makeup, and may be influence by epigenetics,” while the mechanism for vaginal progesterone is probably local “given it is applied directly next to the cervix; hence, the results are it is effective in short cervices.” But those differing mechanisms don’t change the clinical significance of the findings. “One can use vaginal progesterone or 17-OHPC based on patient preference and availability,” Dr. Hedriana said.

The researchers of both studies reported no personal financial or industry disclosures, though Dr. Boelig disclosed that she had taken 17-OHPC and had cerclages during both her pregnancies, which resulted in healthy children today. The PREEMPT trial was funded by the Canadian Institutes of Health Research. The head-to-head trial was funded by the National Institute of Child Health and Development, the March of Dimes, the EW Thrasher Foundation, the PhRMA Foundation, and Covis Pharma, who manufactures the 17-OHPC drug Makena.

This story was updated on 2/8/2022.

The potential effectiveness of using vaginal progesterone to prevent preterm birth in two different populations was the focus of a pair of studies with mixed results at the annual meeting sponsored by the Society for Maternal-Fetal Medicine on Feb. 3. One study found no benefit from vaginal progesterone in those with first trimester bleeding, while the other, in a head-to-head comparison with 17-alpha-hydroxyprogesterone caproate (17-OHPC), found vaginal progesterone performs similarly to 17-OHPC in singleton pregnancies with a history of preterm birth.

While the first study does not suggest any changes in clinical practice, the second one suggests that vaginal progesterone is an alternative to 17-OHPC, as the American College of Obstetricians and Gynecologists currently recommends. SMFM currently only includes 17-OHPC in its guidelines.

“In otherwise low-risk pregnancies with first trimester bleeding, progesterone should not be prescribed for the prevention of miscarriage or prematurity,” Haim A. Abenhaim, MD, MPH, of the Jewish General Hospital at McGill University, Montreal, told attendees in his presentation.

”Publishing the negative result is so important because this helps the overall body of literature reduce the amount of publication bias that exists in the literature,” Michael Richley, MD, an ob.gyn. and maternal-fetal medicine fellow at the University of California, Los Angeles, said in an interview. Dr. Richley was not involved in the research but attended the presentation.
 

Vaginal progesterone for first trimester bleeding

Most preterm birth occurs in pregnancies with no identifiable risk factors, but first-trimester bleeding may indicate subchorionic hemorrhage from placental detachment, which can increase the risk of preterm birth. Other risk factors where progesterone has previously shown effectiveness in reducing preterm birth risk include short cervix and a history of prior preterm birth.

The first study (PREEMPT) was a double-blind, randomized controlled trial conducted at six Canadian hospitals with 533 women. The participants all experienced bleeding within the first 14 weeks of pregnancy and a documented subchorionic hemorrhage. The trial excluded those who already required progesterone, had contraindications to progesterone or had an alternate cause of bleeding.

The intervention group included 264 women randomly assigned to use 200 mg of micronized progesterone administered with a vaginal suppository at bedtime, while the placebo group included 269 women who used a vaginal suppository with no medication, both administered until 34 weeks of pregnancy. The groups were not significantly different in age, race, or former pregnancies, live births, and miscarriages. They were also similar in clinical characteristics of bleeding and subchorionic hemorrhage.

The proportion of term births was similar between the progesterone (74.6%) and placebo (70.6%) groups (P =.3), as was the proportion of preterm births (10.2% progesterone vs. 12.3% placebo, P =.46). There were also no significant differences in the secondary outcomes of cramping, hospital admission, bed rest, or preventive measures, including pessary, cerclage, antibiotics, magnesium, and nifedipine. Newborns across both groups were statistically similar in average birth weight and distribution of birth weights and in incidence of neonatal ICU admission or respiratory distress syndrome. Adverse events were similar across both groups.

”The results are not surprising as several studies in the past have shown similar lack of efficacy,” Dr. said. “The pathophysiology of subchorionic hematoma is different from the multifactorial etiologies of spontaneous preterm birth, and given our lack of clear understanding of the actions of progesterone, the lack of efficacy in this subgroup with subchorionic hematoma is not surprising.”

Dr. Richley did note that having a low-risk population to start with may have affected the findings, which might be different in a high-risk population.

“I don’t believe this will change anything within clinical practice. At this time, progesterone is not used in any form in the setting of first trimester threatened abortion by maternal-fetal medicine specialists,” Dr. Richley said. “There may be other subgroups of clinicians who do prescribe progesterone in this setting, and these data should further encourage them to move away from this practice.”

Dr. Abenhaim noted a couple unexpected issues that occurred during the course of the study, such as underreporting of subchorionic hemorrhage with radiologic confirmation that resulted in a smaller population and a change in protocol to include patients with no identifiable secondary source of bleeding. The pandemic also halted enrollment, and the investigators halted the trial when recruitment could have continued since interim analysis showed no likely benefit.

Though first trimester bleeding is associated with a 25%-30% increased risk of miscarriage or preterm birth, the findings showed that progesterone did not prevent miscarriage or prematurity, or increase the live birth rate, in low-risk patients with first trimester bleeding.
 

Vaginal progesterone vs. 17-OHPC

Although a 2017 meta-analysis had found vaginal progesterone to be superior to 17-OHPC in preventing preterm birth, few studies were available, and they had wide confidence intervals. This open-label randomized controlled trial took place at five U.S. sites and included participants who had a singleton pregnancy less than 24 weeks along and a history of singleton preterm birth between 16 and 37 weeks. The trials excluded those with placenta previa or accreta, preterm labor, preterm premature rupture of the membranes, clinical chorioamnionitis, or a major fetal anomaly or chromosomal disorder.

Among 205 women initially randomized, 94 in each group completed the trial, either inserting 200 mg of micronized progesterone daily with a vaginal suppository or receiving 250 mg of weekly intramuscular injections of 17-OHPC from 16 to 36 weeks’ gestation. The only significant difference between the groups in demographics or clinical features was that the vaginal progesterone group had a higher proportion of multiple past preterm births (33%) compared with the 17-OHPC group (17%). Cervical length and use of cerclage were also similar between the groups.

Though 30.9% of the vaginal progesterone group delivered preterm before 37 weeks, compared with 38.3% in the 17-OHPC group, the difference was not significant (P =.28). There was a borderline statistical difference between gestational age at delivery: 37.4 weeks in the vaginal progesterone group versus 36.3 weeks in the 17-OHPC group (P =.047). Neonatal outcomes were clinically similar between the two groups. Therapy initiation did slightly differ between the groups, with an average start 1 gestational week earlier in the vaginal progesterone group (16.9 vs. 17.8, P =.001) and a higher proportion of patients in the 17-OHPC group initiating therapy after 20 weeks (16.5% vs. 2.2%, P =.001). Adherence was otherwise similar between the groups, and the groups reported similar rates and types of side effects.

The trial did not meet the primary endpoint of vaginal progesterone reducing risk of recurrent preterm birth by 50%, compared with 17-OHPC, but it may increase latency to delivery, Rupsa C. Boelig, MD, of Thomas Jefferson University, Philadelphia, told attendees. Though this was the largest trial to compare vaginal progesterone with 17-OHPC for preventing preterm birth, it was underpowered to detect a difference in efficacy, to conduct subgroup analyses, and to assess secondary outcomes, Dr. Boelig noted. “Baseline difference in preterm birth risk may affect apparent relative efficacy of vaginal progesterone.”

Nevertheless, the “totality of evidence appears to be greater for vaginal progesterone,” Dr. Boelig said, making vaginal progesterone an acceptable alternative to 17-OHPC. ACOG recommendations currently include offering either, but SMFM recommendations only mention 17-OHPC.

It’s worth noting, however, that the future of 17-OHPC, a synthetic compound, compared with naturally occurring micronized progesterone, continues to be uncertain following a 2020 study that found no evidence of its efficacy, leading the Food and Drug Administration to withdraw its approval for prevention of preterm birth. ”These findings are important especially in light of the controversy surrounding 17-OHP,” Jenny Mei, MD, a maternal-fetal medicine fellow at UCLA, said in an interview after attending the presentation. “It is also sometimes difficult for patients to commit to weekly 17-OHPC injections, which requires time and many doctors visits, as compared to vaginal progesterone, which patients can administer at home.” Since this study does not have a placebo group, “it does not address the question of the overall efficacy of either medication compared to a control,” Dr. Mei said. ”It is also a somewhat small patient population so the results may change with a larger population. The authors conclude it is worth readdressing the use of vaginal progesterone for these patients.”

Herman L. Hedriana, MD, professor and director of the division of maternal-fetal medicine and the maternal-fetal medicine fellowship program at the University of California, Davis, also pointed out notable differences between the two compounds.

“One has to remember that the formulation and mechanism of action are very different between 17-OHPC and the vaginal application of micronized progesterone. We do not have enough data to say one is superior versus the other,” said Dr. Hedriana, who was not involved in the research. “With 17-OHPC, the mechanism of action appears to be influenced by how the drug is metabolized based on race and ethnicity makeup, and may be influence by epigenetics,” while the mechanism for vaginal progesterone is probably local “given it is applied directly next to the cervix; hence, the results are it is effective in short cervices.” But those differing mechanisms don’t change the clinical significance of the findings. “One can use vaginal progesterone or 17-OHPC based on patient preference and availability,” Dr. Hedriana said.

The researchers of both studies reported no personal financial or industry disclosures, though Dr. Boelig disclosed that she had taken 17-OHPC and had cerclages during both her pregnancies, which resulted in healthy children today. The PREEMPT trial was funded by the Canadian Institutes of Health Research. The head-to-head trial was funded by the National Institute of Child Health and Development, the March of Dimes, the EW Thrasher Foundation, the PhRMA Foundation, and Covis Pharma, who manufactures the 17-OHPC drug Makena.

This story was updated on 2/8/2022.

Low-dose aspirin may increase risk of postpartum bleeding if patients don’t discontinue its use at least 7 days before delivery, but it’s otherwise unclear whether its use increases bleeding risk, according to research presented Feb. 5 at the meeting sponsored by the Society for Maternal-Fetal Medicine.

“These findings were a little surprising to me because we have generally been taught that aspirin is safe to continue up until delivery with minimal risk,” Jenny Mei, MD, a maternal-fetal medicine fellow at the University of California, Los Angeles, said in an interview after attending the presentation. “Theoretically it makes sense that it may increase bleeding risk, but multiple studies in the past analyzing its use with gynecological surgery show minimal risk, which was conferred to the obstetrical population as well.”

She noted, however, that patients prescribed low-dose aspirin already have risk factors that may increase their risk of postpartum bleeding, and the study’s finding of possible increased risk was not statistically significant after accounting for those confounders. “I wouldn’t change my practice management over it, but it does raise awareness that all interventions likely come with some risk,” Dr. Mei said.

Hypertensive disorders of pregnancy are responsible for 6.6% of U.S. pregnancy-related deaths. The SMFM currently recommends low-dose aspirin starting at 12 weeks’ gestation in patients at high risk for preeclampsia, which includes people with multifetal gestation, chronic hypertension, pregestational diabetes, renal disease, autoimmune disease, or a history of preeclampsia. However, previous research has shown mixed results on the safety of low-dose aspirin in terms of bleeding risk, Kelsey White, MD, a second-year maternal-fetal medicine fellow of the Yale University, New Haven, Conn., told attendees.

This retrospective study compared a bleeding composite endpoint among those who did and did not take low-dose aspirin between January 2018 and April 2021. The composite included an estimated blood loss of greater than 1,000 mL, postpartum hemorrhage based on ICD-9/10 code diagnosis, and red blood cell transfusion. The researchers also compared bleeding risk within the aspirin group based on discontinuation at greater or less than 7 days before delivery.

Among 16,980 patients, 11.3% were prescribed low-dose aspirin. The patients prescribed low-dose aspirin significantly differed from those not prescribed it in all demographic and clinical characteristics except placenta accreta spectrum. The average age of the aspirin group was 39 years, compared with 24 years in the nonaspirin group (P < .01). More of the aspirin group patients were Hispanic and Black, and 52.3% of patients taking aspirin had a body mass index greater than 30 kg/m², compared with 22.9% of the nonaspirin group. Rates of diabetes, lupus, fibroids, nonaspirin anticoagulation use, cesarean delivery, and preterm delivery were all greater in the aspirin group.

In addition, 43.9% of the patients in the aspirin group had a hypertensive disorder, including 20.2% with preeclampsia, compared with 17.1% with hypertensive disorders, including 6.2% with preeclampsia, in the group not taking aspirin (P < .0001). “This shows that a high-risk population was prescribed aspirin, which correlates to the recommended prescription guidelines,” Dr. White said.

The postpartum bleeding composite outcome occurred in 14.7% of patients in the low-dose aspirin group, compared with 9.2% of patients in the nonaspirin group, for an unadjusted 1.7 times greater risk of bleeding (95% confidence interval, 1.49-1.96). After adjustment for confounders, the risk declined and was no longer statistically significant (aOR = 1.15; 95% CI, 0.98-1.34).

Meanwhile, 15% of those who discontinued aspirin within 7 days of delivery had postpartum bleeding, compared with 9% of those who discontinued aspirin at 7 or more days before delivery (P = .03).

Therefore, while the study found only a possible, nonsignificant association between low-dose aspirin and postpartum bleeding, risk of bleeding was significantly greater among those who discontinued aspirin only in the last week before delivery.

”Our study is timely and supports a recent Swedish study [that] found an increased risk of intrapartum bleeding, postpartum hemorrhage, and postpartum hematoma,” Dr. White said. She also noted that the United States Preventive Services Task Force changed their recommendation in 2021 for low-dose aspirin prophylaxis for cardiovascular disease.

“They now recommend against the use of low-dose aspirin for prevention in adults without a history of cardiovascular disease,” Dr. White said. “The change in recommendations came after recent randomized control trials showed that low-dose aspirin had very little benefit and may increase the risk of bleeding.”

However, Dr. White added that they “do not believe this study should be used to make any clinical decisions.” While the study had a large sample size, it was limited by its retrospective reliance on EMR data, including the EMR medication list, and the researchers couldn’t assess patient compliance or patient use of over-the-counter aspirin not recorded in the EMR.

Deirdre Lyell, MD, a professor of maternal-fetal medicine at Stanford (Calif.) University, agreed that the findings should not impact clinical practice given its limitations.

“The investigators could not entirely identify who stopped low-dose aspirin and when. When they estimated timing of stoppage of low-dose aspirin, their data suggested a small benefit among those who discontinued it at least 7 days before delivery, though this should be interpreted with caution, given the potential inaccuracy in these data,” Dr. Lyell, who was not involved in the study, said in an interview. “Their study did not examine factors that should be used to confirm if there are real differences in blood loss, such as changes in blood counts before and after delivery, or more use of medications that we use to stop heavy bleeding.”

In fact, Dr. Lyell noted, other research at the SMFM meeting found ”that low-dose aspirin is not used frequently enough in patients who might benefit, such as those at high risk for preeclampsia,” she said. ”Low-dose aspirin among those at increased risk has been shown to reduce rates of preeclampsia, reducing the likelihood of risky situations for moms and babies.”

The authors had no disclosures. Dr. Lyell has consulted for Bloomlife, a uterine contraction and fetal monitor. Dr. White and Dr. Mei had no disclosures.
 

Low-dose aspirin may increase risk of postpartum bleeding if patients don’t discontinue its use at least 7 days before delivery, but it’s otherwise unclear whether its use increases bleeding risk, according to research presented Feb. 5 at the meeting sponsored by the Society for Maternal-Fetal Medicine.

“These findings were a little surprising to me because we have generally been taught that aspirin is safe to continue up until delivery with minimal risk,” Jenny Mei, MD, a maternal-fetal medicine fellow at the University of California, Los Angeles, said in an interview after attending the presentation. “Theoretically it makes sense that it may increase bleeding risk, but multiple studies in the past analyzing its use with gynecological surgery show minimal risk, which was conferred to the obstetrical population as well.”

She noted, however, that patients prescribed low-dose aspirin already have risk factors that may increase their risk of postpartum bleeding, and the study’s finding of possible increased risk was not statistically significant after accounting for those confounders. “I wouldn’t change my practice management over it, but it does raise awareness that all interventions likely come with some risk,” Dr. Mei said.

Hypertensive disorders of pregnancy are responsible for 6.6% of U.S. pregnancy-related deaths. The SMFM currently recommends low-dose aspirin starting at 12 weeks’ gestation in patients at high risk for preeclampsia, which includes people with multifetal gestation, chronic hypertension, pregestational diabetes, renal disease, autoimmune disease, or a history of preeclampsia. However, previous research has shown mixed results on the safety of low-dose aspirin in terms of bleeding risk, Kelsey White, MD, a second-year maternal-fetal medicine fellow of the Yale University, New Haven, Conn., told attendees.

This retrospective study compared a bleeding composite endpoint among those who did and did not take low-dose aspirin between January 2018 and April 2021. The composite included an estimated blood loss of greater than 1,000 mL, postpartum hemorrhage based on ICD-9/10 code diagnosis, and red blood cell transfusion. The researchers also compared bleeding risk within the aspirin group based on discontinuation at greater or less than 7 days before delivery.

Among 16,980 patients, 11.3% were prescribed low-dose aspirin. The patients prescribed low-dose aspirin significantly differed from those not prescribed it in all demographic and clinical characteristics except placenta accreta spectrum. The average age of the aspirin group was 39 years, compared with 24 years in the nonaspirin group (P < .01). More of the aspirin group patients were Hispanic and Black, and 52.3% of patients taking aspirin had a body mass index greater than 30 kg/m², compared with 22.9% of the nonaspirin group. Rates of diabetes, lupus, fibroids, nonaspirin anticoagulation use, cesarean delivery, and preterm delivery were all greater in the aspirin group.

In addition, 43.9% of the patients in the aspirin group had a hypertensive disorder, including 20.2% with preeclampsia, compared with 17.1% with hypertensive disorders, including 6.2% with preeclampsia, in the group not taking aspirin (P < .0001). “This shows that a high-risk population was prescribed aspirin, which correlates to the recommended prescription guidelines,” Dr. White said.

The postpartum bleeding composite outcome occurred in 14.7% of patients in the low-dose aspirin group, compared with 9.2% of patients in the nonaspirin group, for an unadjusted 1.7 times greater risk of bleeding (95% confidence interval, 1.49-1.96). After adjustment for confounders, the risk declined and was no longer statistically significant (aOR = 1.15; 95% CI, 0.98-1.34).

Meanwhile, 15% of those who discontinued aspirin within 7 days of delivery had postpartum bleeding, compared with 9% of those who discontinued aspirin at 7 or more days before delivery (P = .03).

Therefore, while the study found only a possible, nonsignificant association between low-dose aspirin and postpartum bleeding, risk of bleeding was significantly greater among those who discontinued aspirin only in the last week before delivery.

”Our study is timely and supports a recent Swedish study [that] found an increased risk of intrapartum bleeding, postpartum hemorrhage, and postpartum hematoma,” Dr. White said. She also noted that the United States Preventive Services Task Force changed their recommendation in 2021 for low-dose aspirin prophylaxis for cardiovascular disease.

“They now recommend against the use of low-dose aspirin for prevention in adults without a history of cardiovascular disease,” Dr. White said. “The change in recommendations came after recent randomized control trials showed that low-dose aspirin had very little benefit and may increase the risk of bleeding.”

However, Dr. White added that they “do not believe this study should be used to make any clinical decisions.” While the study had a large sample size, it was limited by its retrospective reliance on EMR data, including the EMR medication list, and the researchers couldn’t assess patient compliance or patient use of over-the-counter aspirin not recorded in the EMR.

Deirdre Lyell, MD, a professor of maternal-fetal medicine at Stanford (Calif.) University, agreed that the findings should not impact clinical practice given its limitations.

“The investigators could not entirely identify who stopped low-dose aspirin and when. When they estimated timing of stoppage of low-dose aspirin, their data suggested a small benefit among those who discontinued it at least 7 days before delivery, though this should be interpreted with caution, given the potential inaccuracy in these data,” Dr. Lyell, who was not involved in the study, said in an interview. “Their study did not examine factors that should be used to confirm if there are real differences in blood loss, such as changes in blood counts before and after delivery, or more use of medications that we use to stop heavy bleeding.”

In fact, Dr. Lyell noted, other research at the SMFM meeting found ”that low-dose aspirin is not used frequently enough in patients who might benefit, such as those at high risk for preeclampsia,” she said. ”Low-dose aspirin among those at increased risk has been shown to reduce rates of preeclampsia, reducing the likelihood of risky situations for moms and babies.”

The authors had no disclosures. Dr. Lyell has consulted for Bloomlife, a uterine contraction and fetal monitor. Dr. White and Dr. Mei had no disclosures.
 

Low-dose aspirin may increase risk of postpartum bleeding if patients don’t discontinue its use at least 7 days before delivery, but it’s otherwise unclear whether its use increases bleeding risk, according to research presented Feb. 5 at the meeting sponsored by the Society for Maternal-Fetal Medicine.

“These findings were a little surprising to me because we have generally been taught that aspirin is safe to continue up until delivery with minimal risk,” Jenny Mei, MD, a maternal-fetal medicine fellow at the University of California, Los Angeles, said in an interview after attending the presentation. “Theoretically it makes sense that it may increase bleeding risk, but multiple studies in the past analyzing its use with gynecological surgery show minimal risk, which was conferred to the obstetrical population as well.”

She noted, however, that patients prescribed low-dose aspirin already have risk factors that may increase their risk of postpartum bleeding, and the study’s finding of possible increased risk was not statistically significant after accounting for those confounders. “I wouldn’t change my practice management over it, but it does raise awareness that all interventions likely come with some risk,” Dr. Mei said.

Hypertensive disorders of pregnancy are responsible for 6.6% of U.S. pregnancy-related deaths. The SMFM currently recommends low-dose aspirin starting at 12 weeks’ gestation in patients at high risk for preeclampsia, which includes people with multifetal gestation, chronic hypertension, pregestational diabetes, renal disease, autoimmune disease, or a history of preeclampsia. However, previous research has shown mixed results on the safety of low-dose aspirin in terms of bleeding risk, Kelsey White, MD, a second-year maternal-fetal medicine fellow of the Yale University, New Haven, Conn., told attendees.

This retrospective study compared a bleeding composite endpoint among those who did and did not take low-dose aspirin between January 2018 and April 2021. The composite included an estimated blood loss of greater than 1,000 mL, postpartum hemorrhage based on ICD-9/10 code diagnosis, and red blood cell transfusion. The researchers also compared bleeding risk within the aspirin group based on discontinuation at greater or less than 7 days before delivery.

Among 16,980 patients, 11.3% were prescribed low-dose aspirin. The patients prescribed low-dose aspirin significantly differed from those not prescribed it in all demographic and clinical characteristics except placenta accreta spectrum. The average age of the aspirin group was 39 years, compared with 24 years in the nonaspirin group (P < .01). More of the aspirin group patients were Hispanic and Black, and 52.3% of patients taking aspirin had a body mass index greater than 30 kg/m², compared with 22.9% of the nonaspirin group. Rates of diabetes, lupus, fibroids, nonaspirin anticoagulation use, cesarean delivery, and preterm delivery were all greater in the aspirin group.

In addition, 43.9% of the patients in the aspirin group had a hypertensive disorder, including 20.2% with preeclampsia, compared with 17.1% with hypertensive disorders, including 6.2% with preeclampsia, in the group not taking aspirin (P < .0001). “This shows that a high-risk population was prescribed aspirin, which correlates to the recommended prescription guidelines,” Dr. White said.

The postpartum bleeding composite outcome occurred in 14.7% of patients in the low-dose aspirin group, compared with 9.2% of patients in the nonaspirin group, for an unadjusted 1.7 times greater risk of bleeding (95% confidence interval, 1.49-1.96). After adjustment for confounders, the risk declined and was no longer statistically significant (aOR = 1.15; 95% CI, 0.98-1.34).

Meanwhile, 15% of those who discontinued aspirin within 7 days of delivery had postpartum bleeding, compared with 9% of those who discontinued aspirin at 7 or more days before delivery (P = .03).

Therefore, while the study found only a possible, nonsignificant association between low-dose aspirin and postpartum bleeding, risk of bleeding was significantly greater among those who discontinued aspirin only in the last week before delivery.

”Our study is timely and supports a recent Swedish study [that] found an increased risk of intrapartum bleeding, postpartum hemorrhage, and postpartum hematoma,” Dr. White said. She also noted that the United States Preventive Services Task Force changed their recommendation in 2021 for low-dose aspirin prophylaxis for cardiovascular disease.

“They now recommend against the use of low-dose aspirin for prevention in adults without a history of cardiovascular disease,” Dr. White said. “The change in recommendations came after recent randomized control trials showed that low-dose aspirin had very little benefit and may increase the risk of bleeding.”

However, Dr. White added that they “do not believe this study should be used to make any clinical decisions.” While the study had a large sample size, it was limited by its retrospective reliance on EMR data, including the EMR medication list, and the researchers couldn’t assess patient compliance or patient use of over-the-counter aspirin not recorded in the EMR.

Deirdre Lyell, MD, a professor of maternal-fetal medicine at Stanford (Calif.) University, agreed that the findings should not impact clinical practice given its limitations.

“The investigators could not entirely identify who stopped low-dose aspirin and when. When they estimated timing of stoppage of low-dose aspirin, their data suggested a small benefit among those who discontinued it at least 7 days before delivery, though this should be interpreted with caution, given the potential inaccuracy in these data,” Dr. Lyell, who was not involved in the study, said in an interview. “Their study did not examine factors that should be used to confirm if there are real differences in blood loss, such as changes in blood counts before and after delivery, or more use of medications that we use to stop heavy bleeding.”

In fact, Dr. Lyell noted, other research at the SMFM meeting found ”that low-dose aspirin is not used frequently enough in patients who might benefit, such as those at high risk for preeclampsia,” she said. ”Low-dose aspirin among those at increased risk has been shown to reduce rates of preeclampsia, reducing the likelihood of risky situations for moms and babies.”

The authors had no disclosures. Dr. Lyell has consulted for Bloomlife, a uterine contraction and fetal monitor. Dr. White and Dr. Mei had no disclosures.
 

Use of marijuana during pregnancy was associated with symptoms of nausea and vomiting and with use of prescribed antiemetics, according to a study presented Feb. 3 at the meeting sponsored by the Society for Maternal-Fetal Medicine. It’s unclear, however, whether the association suggests that pregnant individuals are using marijuana in an attempt to treat their symptoms or whether the marijuana use is contributing to nausea and vomiting – or neither, Torri D. Metz, MD, of the University of Utah Health in Salt Lake City, told attendees.

“Cannabis use has been increasing among pregnant individuals,” Dr. Metz said. “Reported reasons for use range from habit to perceived benefit for treatment of medical conditions, including nausea and vomiting.” She noted a previous study that found that dispensary employees in Colorado recommended cannabis to pregnant callers for treating of nausea despite no clinical evidence of it being an effective treatment.

”Anecdotally, I can say that many patients have told me that marijuana is the only thing that makes them feel better in the first trimester, but that could also be closely tied to marijuana alleviating their other symptoms, such as anxiety or sleep disturbances,” Ilina Pluym, MD, of the department of maternal-fetal medicine at the University of California, Los Angeles, said in an interview. ”In the brain, marijuana acts to alleviate nausea and vomiting, and it has been used successfully to treat nausea [caused by] chemotherapy,” said Dr. Pluym, who attended the abstract presentation but was not involved in the research. “But in the gut, with long-term marijuana use, it can have the opposite effect, which is what is seen in cannabinoid hyperemesis syndrome.”

Past research that has identified a link between cannabis use and nausea in pregnancy has typically relied on administrative data or self-reporting that are subject to recall and social desirability bias instead of a biomarker to assess cannabis use. This study therefore assessed marijuana use based on the presence of THC-COOH in urine samples and added the element of investigating antiemetic use in the population.

The study enrolled 10,038 nulliparous pregnant patients from eight U.S. centers from 2010 to 2013 who were an average 11 weeks pregnant. All participants completed the Pregnancy-Unique Quantification of Emesis (PUQE) tool at their first study visit and consented to testing of their previously frozen urine samples. The PUQE tool asks participants how often they have experienced nausea, vomiting, or retching or dry heaves within the previous 12 hours. A score of 1-6 is mild, a score of 7-12 is moderate, and a score of 13 or higher is severe.

Overall, 15.8% of participants reported moderate to severe nausea and 38.2% reported mild nausea. A total of 5.8% of participants tested positive for marijuana use based on THC levels in urine. Those with incrementally higher levels of THC, at least 500 ng/mg of creatinine, were 1.6 times more likely to report moderate to severe nausea after accounting for maternal age, body mass index, antiemetic drug use, and gestational age (adjusted odds ratio, 1.6; P < .001). An association did not exist, however, with any level of nausea overall. Those with higher creatinine levels were also 1.9 times more likely to report vomiting and 1.6 times more likely to report dry heaves or retching (P < .001).

About 1 in 10 participants (9.6%) overall had used a prescription antiemetic drug. Antiemetics were more common among those who had used marijuana: 18% of those with detectable THC had used antiemetics, compared with 12% of those without evidence of cannabis use (P < .001). However, most of those who used marijuana (83%) took only one antiemetic.

Among the study’s limitations were its lack of data on the reasons for cannabis use and the fact that it took place before widespread cannabidiol products became available, which meant most participants were using marijuana by smoking it.

Dr. Pluym also pointed out that the overall rate of marijuana use during pregnancy is likely higher today than it was in 2010-2013, before many states legalized its use. “But legalization shouldn’t equal normalization in pregnancy,” she added.

In addition, while the PUQE score assesses symptoms within the previous 12 hours, THC can remain in urine samples anywhere from several days to several weeks after marijuana is used.

”We’re unable to establish cause and effect,” Dr. Metz said, “but what we can conclude is that marijuana use was associated with early pregnancy nausea and vomiting.”

The findings emphasize the need for physicians to ask patients about their use of marijuana and seek to find out why they’re using it, Dr. Metz said. If it’s to treat nausea and vomiting of pregnancy, ob.gyns. should ensure patients are aware of the potential adverse effects of marijuana use in pregnancy and mention safe, effective alternatives. Research from the National Academy of Sciences has shown consistent evidence of decreased fetal growth with marijuana use in pregnancy, but there hasn’t been enough evidence to assess potential long-term neurological effects.

The research was funded by the National Institute on Drug Abuse and the National Institute of Child Health and Human Development. Dr. Metz and Dr. Pluym reported no disclosures.

Use of marijuana during pregnancy was associated with symptoms of nausea and vomiting and with use of prescribed antiemetics, according to a study presented Feb. 3 at the meeting sponsored by the Society for Maternal-Fetal Medicine. It’s unclear, however, whether the association suggests that pregnant individuals are using marijuana in an attempt to treat their symptoms or whether the marijuana use is contributing to nausea and vomiting – or neither, Torri D. Metz, MD, of the University of Utah Health in Salt Lake City, told attendees.

“Cannabis use has been increasing among pregnant individuals,” Dr. Metz said. “Reported reasons for use range from habit to perceived benefit for treatment of medical conditions, including nausea and vomiting.” She noted a previous study that found that dispensary employees in Colorado recommended cannabis to pregnant callers for treating of nausea despite no clinical evidence of it being an effective treatment.

”Anecdotally, I can say that many patients have told me that marijuana is the only thing that makes them feel better in the first trimester, but that could also be closely tied to marijuana alleviating their other symptoms, such as anxiety or sleep disturbances,” Ilina Pluym, MD, of the department of maternal-fetal medicine at the University of California, Los Angeles, said in an interview. ”In the brain, marijuana acts to alleviate nausea and vomiting, and it has been used successfully to treat nausea [caused by] chemotherapy,” said Dr. Pluym, who attended the abstract presentation but was not involved in the research. “But in the gut, with long-term marijuana use, it can have the opposite effect, which is what is seen in cannabinoid hyperemesis syndrome.”

Past research that has identified a link between cannabis use and nausea in pregnancy has typically relied on administrative data or self-reporting that are subject to recall and social desirability bias instead of a biomarker to assess cannabis use. This study therefore assessed marijuana use based on the presence of THC-COOH in urine samples and added the element of investigating antiemetic use in the population.

The study enrolled 10,038 nulliparous pregnant patients from eight U.S. centers from 2010 to 2013 who were an average 11 weeks pregnant. All participants completed the Pregnancy-Unique Quantification of Emesis (PUQE) tool at their first study visit and consented to testing of their previously frozen urine samples. The PUQE tool asks participants how often they have experienced nausea, vomiting, or retching or dry heaves within the previous 12 hours. A score of 1-6 is mild, a score of 7-12 is moderate, and a score of 13 or higher is severe.

Overall, 15.8% of participants reported moderate to severe nausea and 38.2% reported mild nausea. A total of 5.8% of participants tested positive for marijuana use based on THC levels in urine. Those with incrementally higher levels of THC, at least 500 ng/mg of creatinine, were 1.6 times more likely to report moderate to severe nausea after accounting for maternal age, body mass index, antiemetic drug use, and gestational age (adjusted odds ratio, 1.6; P < .001). An association did not exist, however, with any level of nausea overall. Those with higher creatinine levels were also 1.9 times more likely to report vomiting and 1.6 times more likely to report dry heaves or retching (P < .001).

About 1 in 10 participants (9.6%) overall had used a prescription antiemetic drug. Antiemetics were more common among those who had used marijuana: 18% of those with detectable THC had used antiemetics, compared with 12% of those without evidence of cannabis use (P < .001). However, most of those who used marijuana (83%) took only one antiemetic.

Among the study’s limitations were its lack of data on the reasons for cannabis use and the fact that it took place before widespread cannabidiol products became available, which meant most participants were using marijuana by smoking it.

Dr. Pluym also pointed out that the overall rate of marijuana use during pregnancy is likely higher today than it was in 2010-2013, before many states legalized its use. “But legalization shouldn’t equal normalization in pregnancy,” she added.

In addition, while the PUQE score assesses symptoms within the previous 12 hours, THC can remain in urine samples anywhere from several days to several weeks after marijuana is used.

”We’re unable to establish cause and effect,” Dr. Metz said, “but what we can conclude is that marijuana use was associated with early pregnancy nausea and vomiting.”

The findings emphasize the need for physicians to ask patients about their use of marijuana and seek to find out why they’re using it, Dr. Metz said. If it’s to treat nausea and vomiting of pregnancy, ob.gyns. should ensure patients are aware of the potential adverse effects of marijuana use in pregnancy and mention safe, effective alternatives. Research from the National Academy of Sciences has shown consistent evidence of decreased fetal growth with marijuana use in pregnancy, but there hasn’t been enough evidence to assess potential long-term neurological effects.

The research was funded by the National Institute on Drug Abuse and the National Institute of Child Health and Human Development. Dr. Metz and Dr. Pluym reported no disclosures.

Use of marijuana during pregnancy was associated with symptoms of nausea and vomiting and with use of prescribed antiemetics, according to a study presented Feb. 3 at the meeting sponsored by the Society for Maternal-Fetal Medicine. It’s unclear, however, whether the association suggests that pregnant individuals are using marijuana in an attempt to treat their symptoms or whether the marijuana use is contributing to nausea and vomiting – or neither, Torri D. Metz, MD, of the University of Utah Health in Salt Lake City, told attendees.

“Cannabis use has been increasing among pregnant individuals,” Dr. Metz said. “Reported reasons for use range from habit to perceived benefit for treatment of medical conditions, including nausea and vomiting.” She noted a previous study that found that dispensary employees in Colorado recommended cannabis to pregnant callers for treating of nausea despite no clinical evidence of it being an effective treatment.

”Anecdotally, I can say that many patients have told me that marijuana is the only thing that makes them feel better in the first trimester, but that could also be closely tied to marijuana alleviating their other symptoms, such as anxiety or sleep disturbances,” Ilina Pluym, MD, of the department of maternal-fetal medicine at the University of California, Los Angeles, said in an interview. ”In the brain, marijuana acts to alleviate nausea and vomiting, and it has been used successfully to treat nausea [caused by] chemotherapy,” said Dr. Pluym, who attended the abstract presentation but was not involved in the research. “But in the gut, with long-term marijuana use, it can have the opposite effect, which is what is seen in cannabinoid hyperemesis syndrome.”

Past research that has identified a link between cannabis use and nausea in pregnancy has typically relied on administrative data or self-reporting that are subject to recall and social desirability bias instead of a biomarker to assess cannabis use. This study therefore assessed marijuana use based on the presence of THC-COOH in urine samples and added the element of investigating antiemetic use in the population.

The study enrolled 10,038 nulliparous pregnant patients from eight U.S. centers from 2010 to 2013 who were an average 11 weeks pregnant. All participants completed the Pregnancy-Unique Quantification of Emesis (PUQE) tool at their first study visit and consented to testing of their previously frozen urine samples. The PUQE tool asks participants how often they have experienced nausea, vomiting, or retching or dry heaves within the previous 12 hours. A score of 1-6 is mild, a score of 7-12 is moderate, and a score of 13 or higher is severe.

Overall, 15.8% of participants reported moderate to severe nausea and 38.2% reported mild nausea. A total of 5.8% of participants tested positive for marijuana use based on THC levels in urine. Those with incrementally higher levels of THC, at least 500 ng/mg of creatinine, were 1.6 times more likely to report moderate to severe nausea after accounting for maternal age, body mass index, antiemetic drug use, and gestational age (adjusted odds ratio, 1.6; P < .001). An association did not exist, however, with any level of nausea overall. Those with higher creatinine levels were also 1.9 times more likely to report vomiting and 1.6 times more likely to report dry heaves or retching (P < .001).

About 1 in 10 participants (9.6%) overall had used a prescription antiemetic drug. Antiemetics were more common among those who had used marijuana: 18% of those with detectable THC had used antiemetics, compared with 12% of those without evidence of cannabis use (P < .001). However, most of those who used marijuana (83%) took only one antiemetic.

Among the study’s limitations were its lack of data on the reasons for cannabis use and the fact that it took place before widespread cannabidiol products became available, which meant most participants were using marijuana by smoking it.

Dr. Pluym also pointed out that the overall rate of marijuana use during pregnancy is likely higher today than it was in 2010-2013, before many states legalized its use. “But legalization shouldn’t equal normalization in pregnancy,” she added.

In addition, while the PUQE score assesses symptoms within the previous 12 hours, THC can remain in urine samples anywhere from several days to several weeks after marijuana is used.

”We’re unable to establish cause and effect,” Dr. Metz said, “but what we can conclude is that marijuana use was associated with early pregnancy nausea and vomiting.”

The findings emphasize the need for physicians to ask patients about their use of marijuana and seek to find out why they’re using it, Dr. Metz said. If it’s to treat nausea and vomiting of pregnancy, ob.gyns. should ensure patients are aware of the potential adverse effects of marijuana use in pregnancy and mention safe, effective alternatives. Research from the National Academy of Sciences has shown consistent evidence of decreased fetal growth with marijuana use in pregnancy, but there hasn’t been enough evidence to assess potential long-term neurological effects.

The research was funded by the National Institute on Drug Abuse and the National Institute of Child Health and Human Development. Dr. Metz and Dr. Pluym reported no disclosures.

In the country with one of the highest rates of preterm birth in the world, these early deliveries dropped by 24% with a simple intervention: chewing gum with xylitol during pregnancy. The decrease in preterm births was linked to improvement in oral health, according to research presented at the meeting sponsored by the Society for Maternal-Fetal Medicine.

Although the findings, from a randomized controlled trial of women in Malawi, barely reached statistical significance, the researchers also documented a reduction in periodontitis (gum disease) that appears to correlate with the reduction in early deliveries, according to Kjersti Aagaard, MD, PhD, of Baylor College of Medicine and Texas Children’s Hospital, both in Houston.

“For a while, we have known about the association with poor oral health and preterm birth but I am not aware of a study of this magnitude suggesting a simple and effective treatment option,” said Ilina Pluym, MD, an assistant professor in maternal fetal medicine at the University of California, Los Angeles, who attended the presentation. Dr. Pluym called the new data “compelling” and said the study “adds to our possible strategies to treat a condition that causes a significant burden of disease worldwide.” The findings must be replicated, ideally in countries with lower rates of preterm birth and periodontal disease to see if the effect is similar, before broadly implementing this cheap and simple intervention.

Preterm birth is a leading cause of infant mortality and a major underlying cause of health problems in children under 5 worldwide. As many as 42% of children born preterm have a health condition related to their prematurity or do not survive childhood.

About one in five babies in Malawi are born between 26 and 37 weeks, about double the U.S. rate of 10.8% preterm births, which in this country is considered births that occur between 23 and 37 weeks’ gestation. Researchers also chose Malawi for the trial because residents there see preterm birth as a widespread problem that must be addressed, Dr. Aagaard said.

Multiple previous studies have found a link between periodontal disease and deliveries that are preterm or low birth weight, Dr. Aagaard told attendees. However, 11 randomized controlled trials that involved treating periodontal disease did not reduce preterm birth despite improving periodontitis and oral health.

Dr. Aagaard’s team decided to test the effectiveness of xylitol – a natural prebiotic found in fruits, vegetables, and bran – because harmful oral bacteria cannot metabolize the substance, and regular use of xylitol reduces the number of harmful mouth bacteria while increasing the number of good microbes in the mouth. In addition, a study in 2006 found that children up to 4 years old had fewer cavities and ear infections when their mothers chewed gum containing xylitol and other compounds. Dr. Aagaard noted that gums without xylitol do not appear to produce the same improvements in oral health.

Before beginning the trial, Dr. Aagaard’s group spent 3 years doing a “run-in” study to ensure a larger, longer-term trial in Malawi was feasible. That initial study found a reduction in tooth decay and periodontal inflammation with use of xylitol. The researchers also learned that participants preferred gum over lozenges or lollipops. Nearly all the participants (92%) chewed the gum twice daily.

Among 10,069 women who enrolled in the trial, 96% remained in it until the end. Of the initial total, 4,029 participants underwent an oral health assessment at the start of the study, and 920 had a follow-up oral health assessment.

Of the 4,349 women who chewed xylitol gum, 12.6% gave birth before 37 weeks, compared with 16.5% preterm births among the 5,321 women in the control group – a 24% reduction (P = .045). The 16.5% rate among women not chewing gum was still lower than the national rate of 19.6%, possibly related to the education the participants received, according to the researchers.

No statistically significant reduction occurred for births at less than 34 weeks, but the reduction in late preterm births – babies born between 34 and 37 weeks – was also borderline in statistical significance (P = .049). Only 9.9% of women chewing xylitol gum had a late preterm birth compared to 13.5% of women who only received health education.

The researchers estimated it would take 26 pregnant women chewing xylitol gum to prevent one preterm birth. At a cost of $24-$29 per pregnancy for the gum, preventing each preterm birth in a community would cost $623-$754.

The researchers also observed a 30% reduction in newborns weighing less than 2,500 g (5.5 pounds), with 8.9% of low-birth-weight babies born to moms chewing gum and 12.9% of low-birth-weight babies born to those not provided gum (P = .046). They attributed this reduction in low birth weight to the lower proportion of late preterm births. The groups showed no significant differences in stillbirths or newborn deaths.

The researchers did, however, find a significant reduction in periodontitis among the women who chewed xylitol gum who came for follow-up dental visits. The prevalence of periodontal disease dropped from 31% to 27% in those not chewing gum but from 31% to 21% in gum chewers (P = .04).

“This cannot be attributed to overall oral health, as dental caries composite scores did not significantly differ while periodontitis measures did,” Dr. Aagaard said.

One limitation of the trial is that it was randomized by health centers instead by individual women, although the researchers tried to account for differences that might exist between the populations going to different facilities. Nor did the researchers assess how frequently the participants chewed gum – although the fact that the gum-chewing group had better oral health suggests they appear to have done so regularly.

Whether recommending xylitol chewing gum to pregnant women in other countries would affect rates of preterm birth is unclear. The ideal population for an intervention like this is one where the population has a high rate of periodontal disease or other preterm birth risk factors, Dr. Pluym said.

”Preterm birth is multifactorial,” she said. “There are often multiple risk factors and causes to the complex pathophysiological process and a quick fix is not the solution for everyone.”

The study was funded by the Thrasher Research Fund. Dr. Aagaard and Dr. Pluym reported no disclosures.

This story was updated on Feb. 4, 2022.

In the country with one of the highest rates of preterm birth in the world, these early deliveries dropped by 24% with a simple intervention: chewing gum with xylitol during pregnancy. The decrease in preterm births was linked to improvement in oral health, according to research presented at the meeting sponsored by the Society for Maternal-Fetal Medicine.

Although the findings, from a randomized controlled trial of women in Malawi, barely reached statistical significance, the researchers also documented a reduction in periodontitis (gum disease) that appears to correlate with the reduction in early deliveries, according to Kjersti Aagaard, MD, PhD, of Baylor College of Medicine and Texas Children’s Hospital, both in Houston.

“For a while, we have known about the association with poor oral health and preterm birth but I am not aware of a study of this magnitude suggesting a simple and effective treatment option,” said Ilina Pluym, MD, an assistant professor in maternal fetal medicine at the University of California, Los Angeles, who attended the presentation. Dr. Pluym called the new data “compelling” and said the study “adds to our possible strategies to treat a condition that causes a significant burden of disease worldwide.” The findings must be replicated, ideally in countries with lower rates of preterm birth and periodontal disease to see if the effect is similar, before broadly implementing this cheap and simple intervention.

Preterm birth is a leading cause of infant mortality and a major underlying cause of health problems in children under 5 worldwide. As many as 42% of children born preterm have a health condition related to their prematurity or do not survive childhood.

About one in five babies in Malawi are born between 26 and 37 weeks, about double the U.S. rate of 10.8% preterm births, which in this country is considered births that occur between 23 and 37 weeks’ gestation. Researchers also chose Malawi for the trial because residents there see preterm birth as a widespread problem that must be addressed, Dr. Aagaard said.

Multiple previous studies have found a link between periodontal disease and deliveries that are preterm or low birth weight, Dr. Aagaard told attendees. However, 11 randomized controlled trials that involved treating periodontal disease did not reduce preterm birth despite improving periodontitis and oral health.

Dr. Aagaard’s team decided to test the effectiveness of xylitol – a natural prebiotic found in fruits, vegetables, and bran – because harmful oral bacteria cannot metabolize the substance, and regular use of xylitol reduces the number of harmful mouth bacteria while increasing the number of good microbes in the mouth. In addition, a study in 2006 found that children up to 4 years old had fewer cavities and ear infections when their mothers chewed gum containing xylitol and other compounds. Dr. Aagaard noted that gums without xylitol do not appear to produce the same improvements in oral health.

Before beginning the trial, Dr. Aagaard’s group spent 3 years doing a “run-in” study to ensure a larger, longer-term trial in Malawi was feasible. That initial study found a reduction in tooth decay and periodontal inflammation with use of xylitol. The researchers also learned that participants preferred gum over lozenges or lollipops. Nearly all the participants (92%) chewed the gum twice daily.

Among 10,069 women who enrolled in the trial, 96% remained in it until the end. Of the initial total, 4,029 participants underwent an oral health assessment at the start of the study, and 920 had a follow-up oral health assessment.

Of the 4,349 women who chewed xylitol gum, 12.6% gave birth before 37 weeks, compared with 16.5% preterm births among the 5,321 women in the control group – a 24% reduction (P = .045). The 16.5% rate among women not chewing gum was still lower than the national rate of 19.6%, possibly related to the education the participants received, according to the researchers.

No statistically significant reduction occurred for births at less than 34 weeks, but the reduction in late preterm births – babies born between 34 and 37 weeks – was also borderline in statistical significance (P = .049). Only 9.9% of women chewing xylitol gum had a late preterm birth compared to 13.5% of women who only received health education.

The researchers estimated it would take 26 pregnant women chewing xylitol gum to prevent one preterm birth. At a cost of $24-$29 per pregnancy for the gum, preventing each preterm birth in a community would cost $623-$754.

The researchers also observed a 30% reduction in newborns weighing less than 2,500 g (5.5 pounds), with 8.9% of low-birth-weight babies born to moms chewing gum and 12.9% of low-birth-weight babies born to those not provided gum (P = .046). They attributed this reduction in low birth weight to the lower proportion of late preterm births. The groups showed no significant differences in stillbirths or newborn deaths.

The researchers did, however, find a significant reduction in periodontitis among the women who chewed xylitol gum who came for follow-up dental visits. The prevalence of periodontal disease dropped from 31% to 27% in those not chewing gum but from 31% to 21% in gum chewers (P = .04).

“This cannot be attributed to overall oral health, as dental caries composite scores did not significantly differ while periodontitis measures did,” Dr. Aagaard said.

One limitation of the trial is that it was randomized by health centers instead by individual women, although the researchers tried to account for differences that might exist between the populations going to different facilities. Nor did the researchers assess how frequently the participants chewed gum – although the fact that the gum-chewing group had better oral health suggests they appear to have done so regularly.

Whether recommending xylitol chewing gum to pregnant women in other countries would affect rates of preterm birth is unclear. The ideal population for an intervention like this is one where the population has a high rate of periodontal disease or other preterm birth risk factors, Dr. Pluym said.

”Preterm birth is multifactorial,” she said. “There are often multiple risk factors and causes to the complex pathophysiological process and a quick fix is not the solution for everyone.”

The study was funded by the Thrasher Research Fund. Dr. Aagaard and Dr. Pluym reported no disclosures.

This story was updated on Feb. 4, 2022.

In the country with one of the highest rates of preterm birth in the world, these early deliveries dropped by 24% with a simple intervention: chewing gum with xylitol during pregnancy. The decrease in preterm births was linked to improvement in oral health, according to research presented at the meeting sponsored by the Society for Maternal-Fetal Medicine.

Although the findings, from a randomized controlled trial of women in Malawi, barely reached statistical significance, the researchers also documented a reduction in periodontitis (gum disease) that appears to correlate with the reduction in early deliveries, according to Kjersti Aagaard, MD, PhD, of Baylor College of Medicine and Texas Children’s Hospital, both in Houston.

“For a while, we have known about the association with poor oral health and preterm birth but I am not aware of a study of this magnitude suggesting a simple and effective treatment option,” said Ilina Pluym, MD, an assistant professor in maternal fetal medicine at the University of California, Los Angeles, who attended the presentation. Dr. Pluym called the new data “compelling” and said the study “adds to our possible strategies to treat a condition that causes a significant burden of disease worldwide.” The findings must be replicated, ideally in countries with lower rates of preterm birth and periodontal disease to see if the effect is similar, before broadly implementing this cheap and simple intervention.

Preterm birth is a leading cause of infant mortality and a major underlying cause of health problems in children under 5 worldwide. As many as 42% of children born preterm have a health condition related to their prematurity or do not survive childhood.

About one in five babies in Malawi are born between 26 and 37 weeks, about double the U.S. rate of 10.8% preterm births, which in this country is considered births that occur between 23 and 37 weeks’ gestation. Researchers also chose Malawi for the trial because residents there see preterm birth as a widespread problem that must be addressed, Dr. Aagaard said.

Multiple previous studies have found a link between periodontal disease and deliveries that are preterm or low birth weight, Dr. Aagaard told attendees. However, 11 randomized controlled trials that involved treating periodontal disease did not reduce preterm birth despite improving periodontitis and oral health.

Dr. Aagaard’s team decided to test the effectiveness of xylitol – a natural prebiotic found in fruits, vegetables, and bran – because harmful oral bacteria cannot metabolize the substance, and regular use of xylitol reduces the number of harmful mouth bacteria while increasing the number of good microbes in the mouth. In addition, a study in 2006 found that children up to 4 years old had fewer cavities and ear infections when their mothers chewed gum containing xylitol and other compounds. Dr. Aagaard noted that gums without xylitol do not appear to produce the same improvements in oral health.

Before beginning the trial, Dr. Aagaard’s group spent 3 years doing a “run-in” study to ensure a larger, longer-term trial in Malawi was feasible. That initial study found a reduction in tooth decay and periodontal inflammation with use of xylitol. The researchers also learned that participants preferred gum over lozenges or lollipops. Nearly all the participants (92%) chewed the gum twice daily.

Among 10,069 women who enrolled in the trial, 96% remained in it until the end. Of the initial total, 4,029 participants underwent an oral health assessment at the start of the study, and 920 had a follow-up oral health assessment.

Of the 4,349 women who chewed xylitol gum, 12.6% gave birth before 37 weeks, compared with 16.5% preterm births among the 5,321 women in the control group – a 24% reduction (P = .045). The 16.5% rate among women not chewing gum was still lower than the national rate of 19.6%, possibly related to the education the participants received, according to the researchers.

No statistically significant reduction occurred for births at less than 34 weeks, but the reduction in late preterm births – babies born between 34 and 37 weeks – was also borderline in statistical significance (P = .049). Only 9.9% of women chewing xylitol gum had a late preterm birth compared to 13.5% of women who only received health education.

The researchers estimated it would take 26 pregnant women chewing xylitol gum to prevent one preterm birth. At a cost of $24-$29 per pregnancy for the gum, preventing each preterm birth in a community would cost $623-$754.

The researchers also observed a 30% reduction in newborns weighing less than 2,500 g (5.5 pounds), with 8.9% of low-birth-weight babies born to moms chewing gum and 12.9% of low-birth-weight babies born to those not provided gum (P = .046). They attributed this reduction in low birth weight to the lower proportion of late preterm births. The groups showed no significant differences in stillbirths or newborn deaths.

The researchers did, however, find a significant reduction in periodontitis among the women who chewed xylitol gum who came for follow-up dental visits. The prevalence of periodontal disease dropped from 31% to 27% in those not chewing gum but from 31% to 21% in gum chewers (P = .04).

“This cannot be attributed to overall oral health, as dental caries composite scores did not significantly differ while periodontitis measures did,” Dr. Aagaard said.

One limitation of the trial is that it was randomized by health centers instead by individual women, although the researchers tried to account for differences that might exist between the populations going to different facilities. Nor did the researchers assess how frequently the participants chewed gum – although the fact that the gum-chewing group had better oral health suggests they appear to have done so regularly.

Whether recommending xylitol chewing gum to pregnant women in other countries would affect rates of preterm birth is unclear. The ideal population for an intervention like this is one where the population has a high rate of periodontal disease or other preterm birth risk factors, Dr. Pluym said.

”Preterm birth is multifactorial,” she said. “There are often multiple risk factors and causes to the complex pathophysiological process and a quick fix is not the solution for everyone.”

The study was funded by the Thrasher Research Fund. Dr. Aagaard and Dr. Pluym reported no disclosures.

This story was updated on Feb. 4, 2022.

Almost 4 years had passed since Pearl Harbor forced the United States into the Second World War when three military and government services members went to the American Psychiatric Association with a plea: They needed soldiers who could pass the military’s mental and emotional health screening.

The military had rejected or discharged more than 2.5 million servicemen and volunteers on mental health grounds, and frustrated psychiatrists in the service didn’t know where else to turn but to their century-old professional psychiatric organization.

But the APA had grown so large and unwieldy by then that its size, bureaucracy, and singular focus on research left few resources for helping solve an urgent national mental health problem, no matter how worthy it was.

“At the time, the APA was kind of the face of organized psychiatry, but it was organized in a way that did not lend itself to addressing the needs of the military,” said Jack W. Bonner III, MD, professor emeritus of psychiatry at the University of South Carolina, Greenville. “It was considered sort of a stodgy organization that really wasn’t nimble enough to reorganize to look at those needs at that point in time.”

And that, the military psychiatrists decided, would not do. Desperate to solve the problem, they took matters into their own hands.

Nearly 2 years later, 15 psychiatrists, mostly military or ex-military, gathered in the hotel room of the U.S. Army Medical Corps chief of neuropsychiatry the night before the annual APA conference. It was 1946, and America had won the war – but with a huge toll on mental health, both in and out of the military. Aside from veterans’ “shell shock” and the specter of inadequate troops for potential future conflicts, huge social shifts had occurred during the war, and public mental health hospitals and community resources had deteriorated just as demand for psychiatrists and mental health personnel well outstripped supply.

If the APA wasn’t going to tackle these problems head on, the 15 psychiatrists decided, they would force it to, and they enshrined that goal in the name they gave themselves: the Group for the Advancement of Psychiatry. Two days later, three of them challenged incumbent APA officers in elections and won. The infiltration of these “Young Turks,” as they thought of themselves, had begun. From that point forward, GAP members have frequently held APA leadership positions, and APA leaders have often gone on to join GAP. Gradually, the smaller upstart organization nudged the behemoth toward more involvement with social issues, but GAP remains more nimble given its size.

“The APA is a pretty leviathan organization and can’t deal with issues in the same way a smaller organization can, and GAP can fulfill that role of being much more responsive to contemporary issues,” said Dr. Bonner, who is a member of GAP’s planning, marketing, and communications committee.
 

The think tank of psychiatry

If it seems strange today that such progressivism arose from military medical officers, equally striking is how that nascent group has improbably grown from its modest, pragmatic beginnings into a psychiatry “think tank” today. Now in its 75th year, GAP can boast of its influence at the locus of nearly every intersection of society and psychiatry, from mental health care in prisons to use of controversial treatments such as shock therapy, from racial tensions to gender inequality, from medical school curricula to mental institution standards, from LBGTQ rights to climate change.

“We’re not here to do the latest double-blind, placebo-controlled research on things,” said Lawrence S. Gross, MD, president of GAP, professor of clinical psychiatry and the behavioral sciences at the University of Southern California, Los Angeles, and a member of the committee on psychopharmacology. “It’s more for leaders to think about issues in different areas that affect the field of psychiatry and how they interface with society.”

Or, more simply, “GAP is a group that predominantly exists for one major purpose, and that is to add to the body of knowledge in the field,” said Sy Saeed, MD, MS, chair of the department of psychiatry at East Carolina University, Greenville, N.C., and chair of the group’s administration and leadership committee.

And the organization doesn’t shy from controversial topics, either, such as examining direct-to-consumer marketing and when patients should stop antidepressant therapy.

“We’re very good at getting marketed to on when to start medications, but how good are we at actually timing when to cut back on them? How long is long enough to treat?” Dr. Gross asked. The organization continues to have “an undercurrent of recognizing and fostering change and making people aware of things that may be controversial at times but also further the field by looking at these different areas of psychiatry.”

Despite the group’s relatively small size of about 200 members, its impact touches nearly everyone in the profession, whether they realize it or not. And though the group certainly has its weaknesses – such as steep membership fees that may deter some from joining and its need to improve membership diversity – GAP actively seeks ways to address these internal challenges just as it does external ones.

“It’s probably one of the best-kept secrets in psychiatry,” Dr. Gross said. But it’s a secret the members want out. That’s one reason members consider the organization’s crown jewel to be its fellowship program. In fact, Steven S. Sharfstein, MD, MPA, a former GAP president, clinical professor of psychiatry at the University of Maryland, Baltimore, and chair of the planning, marketing, and communications committee, did not formally join GAP until the 1980s. But he first became involved with the group as a resident in the fellowship program in 1969.

In its current incarnation, 12 fellows spend 2 years as working members of GAP, assigned to one of its committees to put in work just like every other member is expected to do, but they reap the wisdom and mentorship of its members at the same time.

One thing that makes GAP so special to its members is the ability “to mentor young psychiatrists, going from generation to generation trying to identify leaders and facilitate their growth,” Dr. Gross said. And that process, through not only the fellowship program but also through the members’ diversity of ages and career stages, sustains the organization’s vigor.

“Its strength is that you create this continuum where senior people get to mentor people who are early in their career, and this way, the knowledge continues,” Dr. Saaed said.
 

Creation, not death, by committee

In the early years, GAP’s longevity was in question. Once it had successfully steered the APA toward taking more action to address social problems, did it still have a role to play? A majority of members decided that it did. “New problems arose as old ones were solved,” wrote the late Albert Deutsch in an early history of GAP, and “some steps which were confidently expected to repair an ill or defect did not turn out to be completely effective.” In its first decade, GAP members led the APA to establish new medical director and director of information positions, to improve professional standards and facilitate improvement of mental health facilities, and to expand training.

But where GAP really excelled was in developing projects, something the APA wasn’t well-suited to do, explained Carol C. Nadelson, MD, professor of psychiatry at Harvard Medical School, Boston, a member of the gender and mental health committee, and a past president of GAP. And the breadth of those projects has “expanded as the field has changed and evolved,” said Dr. Nadelson, the first woman president of the APA.

Those projects, the beating heart of GAP’s work, come from its specialized working committees, groups of 6-12 members who spend a couple years focused on a single question or problem in psychiatry that the committee has decided needs attention. The number of committees has grown from 9 at its founding to 32 today, shrinking and expanding as society’s needs demand. Each committee looks for an area it thinks is important and needs attention or updating and then decides how to proceed in addressing it. This structure as a confederation of committees differs greatly from other medical organizations.

“Committees really function in an autonomous, almost independent manner,” Dr. Bonner said. “They control their work, what they do, and how they do it, and the executive structure of the organization has very little impact on those individual committees.”

It’s only when a committee produces whatever project it’s working on that it’s disseminated to the rest of the organization for review.

“The fact that it’s such a federated organization is both a strength and a weakness,” said Roberto Lewis-Fernández, MD, professor of clinical psychiatry at Columbia University, New York, and chair of the cultural psychiatry committee. The tension between becoming too siloed within a committee and needing some sense of greater unity and the cross-pollination that provides is always present, but it’s perhaps also part of the organization’s vibrancy as it constantly seeks the right balance.

It also sometimes allows for fruitful collaborations, such as a recent publication produced by both the religion committee and the LGBTQ+ committee on helping LGBTQ+ teenagers and communities of faith, pointed out Jack Drescher, MD, a GAP past president who serves as clinical professor of psychiatry at Columbia University, and a member of the LGBTQ and media committees.

GAP is also unique in expecting every member to actively put in work toward its mission.

“If you join the APA, you can do absolutely nothing, or you can go to a conference once a year and learn from other people, but you don’t have to be active,” said Gail Robinson, MD, professor of psychiatry and ob.gyn. at the University of Toronto and chair of GAP’s gender and mental health committee. But if you’re a GAP member who isn’t contributing, expect to hear from someone asking how they can help you figure out how you can contribute.

Expecting that much work from members means meeting more often than most medical societies. Except during the pandemic, GAP members have always met twice a year for a long weekend in White Plains, N.Y., to focus almost exclusively on the committees’ current projects. Each meeting allows members “to immerse themselves in thinking about topics that the various committees find of interest and think might be of interest to the rest of the world,” said David Adler, MD, a professor of psychiatry and medicine at Tufts Medical Center in Boston, and chair of the GAP publication board. Whereas APA meetings are massive, frenetic events focused primarily on new research and continuing education for tens of thousands of attendees, GAP meetings are more intimidate and meditative, “a time in which the leaders can exchange ideas in a more private setting,” Dr. Adler said.

What makes GAP’s meetings so special is that they provide a temporary refuge with the explicit goal of encouraging unhurried discussion and deliberation about big ideas that matter, Dr. Robinson said.

“One of the enjoyable parts of GAP is that you have time to think,” Dr. Robinson said. “In your regular life, you’re seeing patients, you’re doing research or organizing things, but in GAP, you can sit with a group of like-minded, interested people and toss some ideas around about what’s important right now. What should we be looking at? What is the field not paying enough attention to? And then the ideas bubble up. In a lot of other organizations, you’re doing specific work, some of it political, some in terms of the organization, but to just sort of sit and think about what’s important in your field and what people should know more about is a different kind of feeling.”
 

A force for change

The work GAP produces has had a substantial impact on the field of psychiatry and society in general over the past 7 and a half decades. Consider this list of just a handful of GAP contributions in its first decade.

• Guidance regarding electroconvulsive therapy in 1947, followed by an update, in response to reaction to the first document, in 1950.
• A guide to school integration after Brown v. Board of Education that considered the psychiatric challenges of integration.
• A report for employers on workers with epilepsy for occupational health and safety.
• Publications that raised mental hospital standards in the 1950s.
• A range of action documents used by medical schools, psychology and social work departments and agencies, governmental bodies, courts, industry, public schools, and community health and welfare agencies.

Over the years, GAP’s influence has sometimes been overt – such as publishing the only diagnostic and statistical manual for child psychiatry for years before that material was incorporated into the official DSM. Sometimes it’s just ahead of the curve, such as the women’s mental health committee publishing a paper that reviewed the evidence on “abortion trauma syndrome” and concluding that it doesn’t exist shortly before the American Psychological Association and the U.K.’s Royal College of Psychiatrists published reviews with similar conclusions. In a few instances, GAP has caused shifts in how the APA operates, such as encouraging the larger organization to publish books on mental health, said Dr. Sharfstein, a past president of the APA.

Much of the organization’s impact occurs through its effects on education, which affects clinical psychiatry at large.“Some reports are very much designed to have an impact on psychiatry education, residency training and curriculum development, which would have a big impact on practice,” Dr. Sharfstein said. An example is the committee on disasters, which examines the best ways for mental health professionals to respond to and mitigate the mental health fallout from the consequences of natural and manmade disasters.

Most often, though, GAP’s influence is akin to strategically planting very carefully cultivated seeds throughout the academic and clinical media ecosystems and letting them bloom how they will. For example, Dr. Lewis-Fernández described a project the cultural committee published in 2013: a checklist for how a psychiatry research article should address topics related to race, ethnicity, and culture. After reviewing articles in the field and their methodologies, the group developed a checklist of best practices and tested them with articles in the field to see how the checklist held up before publishing it.

“Initially, some people read it, some people didn’t, but over time, it’s gotten picked up, and it’s now about to be used in a journal on psychiatric services as a guide to authors and reviews on the appropriate use of these concepts,” Dr. Lewis-Fernández said.

GAP’s influence also blooms through the cross-pollination that occurs at meetings, where leaders in psychiatry from all across the country come together, discuss ideas, and then take new ideas back to their universities, where they teach them to their residents. Perhaps the best example of this influence in recent years has been a increasing shift in teaching about LGBTQ+ issues.

“There’s an underrepresentation of teaching about LGBTQ+ issues in many psychiatric training programs in many medical schools,” Dr. Drescher said. The organization has worked to raise awareness about these gaps in the education of medical students and mental health professionals and then address it, such as designing an online module curriculum in the early 2000s for how to teach residents about LGBTQ+ mental health issues and then updating it as needed.

Perhaps GAP’s greatest lifetime achievement is forcing the field of psychiatry to confront the fact that it – and its patients – do not stand apart from the society in which they exist.

“People aren’t just psychiatric disorders. They live in society, and society has an impact on them, and that affects how people cope,” Dr. Robinson said. That was once a radical concept, but now “psychiatry as a whole has moved to be more broadly expansive” just as GAP itself has broadened its scope, as evidenced by the wide range of committees, more than triple what the organization had at its founding. “GAP was really at the vanguard of that expansion into the recognizing the need to consider the interaction between the individual and the environment they live in socially.”

That’s never been more true than during the COVID-19 pandemic, contributing to perhaps the greatest mental health crisis in the nation’s history since World War II. But the pandemic hasn’t slowed down GAP’s work. In fact, in some ways, the pandemic has facilitated the group’s ability to meet more often virtually and focus on acute issues the pandemic itself has caused. The psychopathology committee published one paper on the impact of telehealth on treating the chronic mentally ill during COVID, and another delved into rethinking where things stand with institutional racism within psychiatry. The women’s mental health committee published articles on the impact of COVID on pregnant and postpartum women, and the impact of COVID on minority women.
 

Confronting challenges within, too

For all its positive influence, GAP has its weaknesses as well. Two of the biggest barriers to membership, for example, are the steep dues and travel to the twice annual meetings, Dr. Lewis-Fernández said.

The membership dues are not needlessly high: The organization relies on philanthropy and dues for all of its activities, most recently, secured endowments from institutional and individual donors to fund all of the GAP fellows, Dr. Gross said.

“With a low number of members, the cost is larger per member,” Dr. Bonner explained. In fact, GAP has only recently overcome a period of financial uncertainty, now finally on solid ground in terms of fundings.

While the dues can be onerous, Dr. Lewis-Fernández said the organization has been actively thinking about ways to reduce it, particularly for those who may need help if traveling from farther away or younger-career individuals, such as those without tenure or with young families.

It can also be difficult for the organization to attract diverse members from different racial and ethnic groups when leaders in psychiatry from those backgrounds are courted by many other groups, or just to attract younger members in general, but GAP continues to seek ways to overcome those challenges.

“The majority of people in GAP have some kind of academic interest, and the nature of being an early career psychiatrist in academia is that you have to publish to get promoted,” Dr. Bonner said. GAP’s historical practice of producing publications by committee without individual attribution was a disincentive to those early-career folks. “More recently, we’ve changed that so that now individuals can put their names on their product, which has eliminated that particular barriers for young people.”

As the organization continues to seek ways to address those issues, it also faces the same challenges as every other scientific group: Staying relevant in the new, and constantly changing, media landscape.

“It’s an interesting evolution because it started off with books and monographs for many, many years,” Dr. Robinson said, “and then it kind of moved away from that to more articles.” More recently, some committees have returned to writing books while others explore other forms of media to keep up with the times. Long gone are the days when a committee might spend 2-10 years producing one monograph.

“In today’s world, you can’t be relevant operating that way,” said Dr. Bonner, noting that some committees have produced videos or podcasts.

But the sheer amount of information out there is intimidating as well. “Nowadays, a lot of people get their information off the Internet, and how do you actually sift through that?” Dr. Saeed said. “How you find signal in this noise is a whole different thing now, so how GAP produces its information is at that trajectory right now. Should we be producing more electronic books? What should be our peer-review process? How do we make sure the information is current? If we are about sharing information and generating new knowledge, what’s the best way of disseminating that?”

A testament to the organization’s willingness to confront that challenge, however, is its exploration of every possible platform – even those well outside the traditional ones. The climate committee, for example, recently set about addressing climate anxiety in children, but they didn’t produce a report or develop a teaching module or even develop a series of podcasts. Instead, the committee collaborated with Jeremy D. Wortzel, MPhil, an MD and MPH candidate at the University of Pennsylvania, Philadelphia, and Lena K. Champlin, a doctoral candidate in environmental science at Drexel University, Philadelpha, to write a children’s book. “Coco’s Fire: Changing Climate Anxiety into Climate Action” was published in October 2021.
 

GAP continues to leave its mark

For all the work that members put into the organization, members say they reap substantial benefits as well. Dr. Saaed recalls feeling flattered when invited to join the organization because of how influential it is and the opportunity to work with so many leaders in psychiatry. “When you come to GAP committee meetings, you would run into people whose book or research you might have read and who are very prominent in the field,” he said.

Dr. Drescher credited GAP with helping him develop his voice and polish his editing skills, which later aided him when he became editor of the Journal of Gay and Lesbian Mental Health. When the LGBTQ+ committee shifted from reports to writing op-eds, members learned how to write opinion pieces and then teach members of other committees those skills, resulting in GAP-produced op-eds in consumer and trade publications. And then there are the intangible rewards that leave a profound impact on members.

Some members see GAP as central to their professional lives and perhaps legacies.

“Outside of the medical center, this has probably been the most important professional organization of my career, and I think there are a lot of people who feel that way,” Dr. Adler said. “It’s a very unique experience, and the goal is to examine today’s critical issues and say something about them in a way in which maybe the world will take notice.”

Almost 4 years had passed since Pearl Harbor forced the United States into the Second World War when three military and government services members went to the American Psychiatric Association with a plea: They needed soldiers who could pass the military’s mental and emotional health screening.

The military had rejected or discharged more than 2.5 million servicemen and volunteers on mental health grounds, and frustrated psychiatrists in the service didn’t know where else to turn but to their century-old professional psychiatric organization.

But the APA had grown so large and unwieldy by then that its size, bureaucracy, and singular focus on research left few resources for helping solve an urgent national mental health problem, no matter how worthy it was.

“At the time, the APA was kind of the face of organized psychiatry, but it was organized in a way that did not lend itself to addressing the needs of the military,” said Jack W. Bonner III, MD, professor emeritus of psychiatry at the University of South Carolina, Greenville. “It was considered sort of a stodgy organization that really wasn’t nimble enough to reorganize to look at those needs at that point in time.”

And that, the military psychiatrists decided, would not do. Desperate to solve the problem, they took matters into their own hands.

Nearly 2 years later, 15 psychiatrists, mostly military or ex-military, gathered in the hotel room of the U.S. Army Medical Corps chief of neuropsychiatry the night before the annual APA conference. It was 1946, and America had won the war – but with a huge toll on mental health, both in and out of the military. Aside from veterans’ “shell shock” and the specter of inadequate troops for potential future conflicts, huge social shifts had occurred during the war, and public mental health hospitals and community resources had deteriorated just as demand for psychiatrists and mental health personnel well outstripped supply.

If the APA wasn’t going to tackle these problems head on, the 15 psychiatrists decided, they would force it to, and they enshrined that goal in the name they gave themselves: the Group for the Advancement of Psychiatry. Two days later, three of them challenged incumbent APA officers in elections and won. The infiltration of these “Young Turks,” as they thought of themselves, had begun. From that point forward, GAP members have frequently held APA leadership positions, and APA leaders have often gone on to join GAP. Gradually, the smaller upstart organization nudged the behemoth toward more involvement with social issues, but GAP remains more nimble given its size.

“The APA is a pretty leviathan organization and can’t deal with issues in the same way a smaller organization can, and GAP can fulfill that role of being much more responsive to contemporary issues,” said Dr. Bonner, who is a member of GAP’s planning, marketing, and communications committee.
 

The think tank of psychiatry

If it seems strange today that such progressivism arose from military medical officers, equally striking is how that nascent group has improbably grown from its modest, pragmatic beginnings into a psychiatry “think tank” today. Now in its 75th year, GAP can boast of its influence at the locus of nearly every intersection of society and psychiatry, from mental health care in prisons to use of controversial treatments such as shock therapy, from racial tensions to gender inequality, from medical school curricula to mental institution standards, from LBGTQ rights to climate change.

“We’re not here to do the latest double-blind, placebo-controlled research on things,” said Lawrence S. Gross, MD, president of GAP, professor of clinical psychiatry and the behavioral sciences at the University of Southern California, Los Angeles, and a member of the committee on psychopharmacology. “It’s more for leaders to think about issues in different areas that affect the field of psychiatry and how they interface with society.”

Or, more simply, “GAP is a group that predominantly exists for one major purpose, and that is to add to the body of knowledge in the field,” said Sy Saeed, MD, MS, chair of the department of psychiatry at East Carolina University, Greenville, N.C., and chair of the group’s administration and leadership committee.

And the organization doesn’t shy from controversial topics, either, such as examining direct-to-consumer marketing and when patients should stop antidepressant therapy.

“We’re very good at getting marketed to on when to start medications, but how good are we at actually timing when to cut back on them? How long is long enough to treat?” Dr. Gross asked. The organization continues to have “an undercurrent of recognizing and fostering change and making people aware of things that may be controversial at times but also further the field by looking at these different areas of psychiatry.”

Despite the group’s relatively small size of about 200 members, its impact touches nearly everyone in the profession, whether they realize it or not. And though the group certainly has its weaknesses – such as steep membership fees that may deter some from joining and its need to improve membership diversity – GAP actively seeks ways to address these internal challenges just as it does external ones.

“It’s probably one of the best-kept secrets in psychiatry,” Dr. Gross said. But it’s a secret the members want out. That’s one reason members consider the organization’s crown jewel to be its fellowship program. In fact, Steven S. Sharfstein, MD, MPA, a former GAP president, clinical professor of psychiatry at the University of Maryland, Baltimore, and chair of the planning, marketing, and communications committee, did not formally join GAP until the 1980s. But he first became involved with the group as a resident in the fellowship program in 1969.

In its current incarnation, 12 fellows spend 2 years as working members of GAP, assigned to one of its committees to put in work just like every other member is expected to do, but they reap the wisdom and mentorship of its members at the same time.

One thing that makes GAP so special to its members is the ability “to mentor young psychiatrists, going from generation to generation trying to identify leaders and facilitate their growth,” Dr. Gross said. And that process, through not only the fellowship program but also through the members’ diversity of ages and career stages, sustains the organization’s vigor.

“Its strength is that you create this continuum where senior people get to mentor people who are early in their career, and this way, the knowledge continues,” Dr. Saaed said.
 

Creation, not death, by committee

In the early years, GAP’s longevity was in question. Once it had successfully steered the APA toward taking more action to address social problems, did it still have a role to play? A majority of members decided that it did. “New problems arose as old ones were solved,” wrote the late Albert Deutsch in an early history of GAP, and “some steps which were confidently expected to repair an ill or defect did not turn out to be completely effective.” In its first decade, GAP members led the APA to establish new medical director and director of information positions, to improve professional standards and facilitate improvement of mental health facilities, and to expand training.

But where GAP really excelled was in developing projects, something the APA wasn’t well-suited to do, explained Carol C. Nadelson, MD, professor of psychiatry at Harvard Medical School, Boston, a member of the gender and mental health committee, and a past president of GAP. And the breadth of those projects has “expanded as the field has changed and evolved,” said Dr. Nadelson, the first woman president of the APA.

Those projects, the beating heart of GAP’s work, come from its specialized working committees, groups of 6-12 members who spend a couple years focused on a single question or problem in psychiatry that the committee has decided needs attention. The number of committees has grown from 9 at its founding to 32 today, shrinking and expanding as society’s needs demand. Each committee looks for an area it thinks is important and needs attention or updating and then decides how to proceed in addressing it. This structure as a confederation of committees differs greatly from other medical organizations.

“Committees really function in an autonomous, almost independent manner,” Dr. Bonner said. “They control their work, what they do, and how they do it, and the executive structure of the organization has very little impact on those individual committees.”

It’s only when a committee produces whatever project it’s working on that it’s disseminated to the rest of the organization for review.

“The fact that it’s such a federated organization is both a strength and a weakness,” said Roberto Lewis-Fernández, MD, professor of clinical psychiatry at Columbia University, New York, and chair of the cultural psychiatry committee. The tension between becoming too siloed within a committee and needing some sense of greater unity and the cross-pollination that provides is always present, but it’s perhaps also part of the organization’s vibrancy as it constantly seeks the right balance.

It also sometimes allows for fruitful collaborations, such as a recent publication produced by both the religion committee and the LGBTQ+ committee on helping LGBTQ+ teenagers and communities of faith, pointed out Jack Drescher, MD, a GAP past president who serves as clinical professor of psychiatry at Columbia University, and a member of the LGBTQ and media committees.

GAP is also unique in expecting every member to actively put in work toward its mission.

“If you join the APA, you can do absolutely nothing, or you can go to a conference once a year and learn from other people, but you don’t have to be active,” said Gail Robinson, MD, professor of psychiatry and ob.gyn. at the University of Toronto and chair of GAP’s gender and mental health committee. But if you’re a GAP member who isn’t contributing, expect to hear from someone asking how they can help you figure out how you can contribute.

Expecting that much work from members means meeting more often than most medical societies. Except during the pandemic, GAP members have always met twice a year for a long weekend in White Plains, N.Y., to focus almost exclusively on the committees’ current projects. Each meeting allows members “to immerse themselves in thinking about topics that the various committees find of interest and think might be of interest to the rest of the world,” said David Adler, MD, a professor of psychiatry and medicine at Tufts Medical Center in Boston, and chair of the GAP publication board. Whereas APA meetings are massive, frenetic events focused primarily on new research and continuing education for tens of thousands of attendees, GAP meetings are more intimidate and meditative, “a time in which the leaders can exchange ideas in a more private setting,” Dr. Adler said.

What makes GAP’s meetings so special is that they provide a temporary refuge with the explicit goal of encouraging unhurried discussion and deliberation about big ideas that matter, Dr. Robinson said.

“One of the enjoyable parts of GAP is that you have time to think,” Dr. Robinson said. “In your regular life, you’re seeing patients, you’re doing research or organizing things, but in GAP, you can sit with a group of like-minded, interested people and toss some ideas around about what’s important right now. What should we be looking at? What is the field not paying enough attention to? And then the ideas bubble up. In a lot of other organizations, you’re doing specific work, some of it political, some in terms of the organization, but to just sort of sit and think about what’s important in your field and what people should know more about is a different kind of feeling.”
 

A force for change

The work GAP produces has had a substantial impact on the field of psychiatry and society in general over the past 7 and a half decades. Consider this list of just a handful of GAP contributions in its first decade.

• Guidance regarding electroconvulsive therapy in 1947, followed by an update, in response to reaction to the first document, in 1950.
• A guide to school integration after Brown v. Board of Education that considered the psychiatric challenges of integration.
• A report for employers on workers with epilepsy for occupational health and safety.
• Publications that raised mental hospital standards in the 1950s.
• A range of action documents used by medical schools, psychology and social work departments and agencies, governmental bodies, courts, industry, public schools, and community health and welfare agencies.

Over the years, GAP’s influence has sometimes been overt – such as publishing the only diagnostic and statistical manual for child psychiatry for years before that material was incorporated into the official DSM. Sometimes it’s just ahead of the curve, such as the women’s mental health committee publishing a paper that reviewed the evidence on “abortion trauma syndrome” and concluding that it doesn’t exist shortly before the American Psychological Association and the U.K.’s Royal College of Psychiatrists published reviews with similar conclusions. In a few instances, GAP has caused shifts in how the APA operates, such as encouraging the larger organization to publish books on mental health, said Dr. Sharfstein, a past president of the APA.

Much of the organization’s impact occurs through its effects on education, which affects clinical psychiatry at large.“Some reports are very much designed to have an impact on psychiatry education, residency training and curriculum development, which would have a big impact on practice,” Dr. Sharfstein said. An example is the committee on disasters, which examines the best ways for mental health professionals to respond to and mitigate the mental health fallout from the consequences of natural and manmade disasters.

Most often, though, GAP’s influence is akin to strategically planting very carefully cultivated seeds throughout the academic and clinical media ecosystems and letting them bloom how they will. For example, Dr. Lewis-Fernández described a project the cultural committee published in 2013: a checklist for how a psychiatry research article should address topics related to race, ethnicity, and culture. After reviewing articles in the field and their methodologies, the group developed a checklist of best practices and tested them with articles in the field to see how the checklist held up before publishing it.

“Initially, some people read it, some people didn’t, but over time, it’s gotten picked up, and it’s now about to be used in a journal on psychiatric services as a guide to authors and reviews on the appropriate use of these concepts,” Dr. Lewis-Fernández said.

GAP’s influence also blooms through the cross-pollination that occurs at meetings, where leaders in psychiatry from all across the country come together, discuss ideas, and then take new ideas back to their universities, where they teach them to their residents. Perhaps the best example of this influence in recent years has been a increasing shift in teaching about LGBTQ+ issues.

“There’s an underrepresentation of teaching about LGBTQ+ issues in many psychiatric training programs in many medical schools,” Dr. Drescher said. The organization has worked to raise awareness about these gaps in the education of medical students and mental health professionals and then address it, such as designing an online module curriculum in the early 2000s for how to teach residents about LGBTQ+ mental health issues and then updating it as needed.

Perhaps GAP’s greatest lifetime achievement is forcing the field of psychiatry to confront the fact that it – and its patients – do not stand apart from the society in which they exist.

“People aren’t just psychiatric disorders. They live in society, and society has an impact on them, and that affects how people cope,” Dr. Robinson said. That was once a radical concept, but now “psychiatry as a whole has moved to be more broadly expansive” just as GAP itself has broadened its scope, as evidenced by the wide range of committees, more than triple what the organization had at its founding. “GAP was really at the vanguard of that expansion into the recognizing the need to consider the interaction between the individual and the environment they live in socially.”

That’s never been more true than during the COVID-19 pandemic, contributing to perhaps the greatest mental health crisis in the nation’s history since World War II. But the pandemic hasn’t slowed down GAP’s work. In fact, in some ways, the pandemic has facilitated the group’s ability to meet more often virtually and focus on acute issues the pandemic itself has caused. The psychopathology committee published one paper on the impact of telehealth on treating the chronic mentally ill during COVID, and another delved into rethinking where things stand with institutional racism within psychiatry. The women’s mental health committee published articles on the impact of COVID on pregnant and postpartum women, and the impact of COVID on minority women.
 

Confronting challenges within, too

For all its positive influence, GAP has its weaknesses as well. Two of the biggest barriers to membership, for example, are the steep dues and travel to the twice annual meetings, Dr. Lewis-Fernández said.

The membership dues are not needlessly high: The organization relies on philanthropy and dues for all of its activities, most recently, secured endowments from institutional and individual donors to fund all of the GAP fellows, Dr. Gross said.

“With a low number of members, the cost is larger per member,” Dr. Bonner explained. In fact, GAP has only recently overcome a period of financial uncertainty, now finally on solid ground in terms of fundings.

While the dues can be onerous, Dr. Lewis-Fernández said the organization has been actively thinking about ways to reduce it, particularly for those who may need help if traveling from farther away or younger-career individuals, such as those without tenure or with young families.

It can also be difficult for the organization to attract diverse members from different racial and ethnic groups when leaders in psychiatry from those backgrounds are courted by many other groups, or just to attract younger members in general, but GAP continues to seek ways to overcome those challenges.

“The majority of people in GAP have some kind of academic interest, and the nature of being an early career psychiatrist in academia is that you have to publish to get promoted,” Dr. Bonner said. GAP’s historical practice of producing publications by committee without individual attribution was a disincentive to those early-career folks. “More recently, we’ve changed that so that now individuals can put their names on their product, which has eliminated that particular barriers for young people.”

As the organization continues to seek ways to address those issues, it also faces the same challenges as every other scientific group: Staying relevant in the new, and constantly changing, media landscape.

“It’s an interesting evolution because it started off with books and monographs for many, many years,” Dr. Robinson said, “and then it kind of moved away from that to more articles.” More recently, some committees have returned to writing books while others explore other forms of media to keep up with the times. Long gone are the days when a committee might spend 2-10 years producing one monograph.

“In today’s world, you can’t be relevant operating that way,” said Dr. Bonner, noting that some committees have produced videos or podcasts.

But the sheer amount of information out there is intimidating as well. “Nowadays, a lot of people get their information off the Internet, and how do you actually sift through that?” Dr. Saeed said. “How you find signal in this noise is a whole different thing now, so how GAP produces its information is at that trajectory right now. Should we be producing more electronic books? What should be our peer-review process? How do we make sure the information is current? If we are about sharing information and generating new knowledge, what’s the best way of disseminating that?”

A testament to the organization’s willingness to confront that challenge, however, is its exploration of every possible platform – even those well outside the traditional ones. The climate committee, for example, recently set about addressing climate anxiety in children, but they didn’t produce a report or develop a teaching module or even develop a series of podcasts. Instead, the committee collaborated with Jeremy D. Wortzel, MPhil, an MD and MPH candidate at the University of Pennsylvania, Philadelphia, and Lena K. Champlin, a doctoral candidate in environmental science at Drexel University, Philadelpha, to write a children’s book. “Coco’s Fire: Changing Climate Anxiety into Climate Action” was published in October 2021.
 

GAP continues to leave its mark

For all the work that members put into the organization, members say they reap substantial benefits as well. Dr. Saaed recalls feeling flattered when invited to join the organization because of how influential it is and the opportunity to work with so many leaders in psychiatry. “When you come to GAP committee meetings, you would run into people whose book or research you might have read and who are very prominent in the field,” he said.

Dr. Drescher credited GAP with helping him develop his voice and polish his editing skills, which later aided him when he became editor of the Journal of Gay and Lesbian Mental Health. When the LGBTQ+ committee shifted from reports to writing op-eds, members learned how to write opinion pieces and then teach members of other committees those skills, resulting in GAP-produced op-eds in consumer and trade publications. And then there are the intangible rewards that leave a profound impact on members.

Some members see GAP as central to their professional lives and perhaps legacies.

“Outside of the medical center, this has probably been the most important professional organization of my career, and I think there are a lot of people who feel that way,” Dr. Adler said. “It’s a very unique experience, and the goal is to examine today’s critical issues and say something about them in a way in which maybe the world will take notice.”

Almost 4 years had passed since Pearl Harbor forced the United States into the Second World War when three military and government services members went to the American Psychiatric Association with a plea: They needed soldiers who could pass the military’s mental and emotional health screening.

The military had rejected or discharged more than 2.5 million servicemen and volunteers on mental health grounds, and frustrated psychiatrists in the service didn’t know where else to turn but to their century-old professional psychiatric organization.

But the APA had grown so large and unwieldy by then that its size, bureaucracy, and singular focus on research left few resources for helping solve an urgent national mental health problem, no matter how worthy it was.

“At the time, the APA was kind of the face of organized psychiatry, but it was organized in a way that did not lend itself to addressing the needs of the military,” said Jack W. Bonner III, MD, professor emeritus of psychiatry at the University of South Carolina, Greenville. “It was considered sort of a stodgy organization that really wasn’t nimble enough to reorganize to look at those needs at that point in time.”

And that, the military psychiatrists decided, would not do. Desperate to solve the problem, they took matters into their own hands.

Nearly 2 years later, 15 psychiatrists, mostly military or ex-military, gathered in the hotel room of the U.S. Army Medical Corps chief of neuropsychiatry the night before the annual APA conference. It was 1946, and America had won the war – but with a huge toll on mental health, both in and out of the military. Aside from veterans’ “shell shock” and the specter of inadequate troops for potential future conflicts, huge social shifts had occurred during the war, and public mental health hospitals and community resources had deteriorated just as demand for psychiatrists and mental health personnel well outstripped supply.

If the APA wasn’t going to tackle these problems head on, the 15 psychiatrists decided, they would force it to, and they enshrined that goal in the name they gave themselves: the Group for the Advancement of Psychiatry. Two days later, three of them challenged incumbent APA officers in elections and won. The infiltration of these “Young Turks,” as they thought of themselves, had begun. From that point forward, GAP members have frequently held APA leadership positions, and APA leaders have often gone on to join GAP. Gradually, the smaller upstart organization nudged the behemoth toward more involvement with social issues, but GAP remains more nimble given its size.

“The APA is a pretty leviathan organization and can’t deal with issues in the same way a smaller organization can, and GAP can fulfill that role of being much more responsive to contemporary issues,” said Dr. Bonner, who is a member of GAP’s planning, marketing, and communications committee.
 

The think tank of psychiatry

If it seems strange today that such progressivism arose from military medical officers, equally striking is how that nascent group has improbably grown from its modest, pragmatic beginnings into a psychiatry “think tank” today. Now in its 75th year, GAP can boast of its influence at the locus of nearly every intersection of society and psychiatry, from mental health care in prisons to use of controversial treatments such as shock therapy, from racial tensions to gender inequality, from medical school curricula to mental institution standards, from LBGTQ rights to climate change.

“We’re not here to do the latest double-blind, placebo-controlled research on things,” said Lawrence S. Gross, MD, president of GAP, professor of clinical psychiatry and the behavioral sciences at the University of Southern California, Los Angeles, and a member of the committee on psychopharmacology. “It’s more for leaders to think about issues in different areas that affect the field of psychiatry and how they interface with society.”

Or, more simply, “GAP is a group that predominantly exists for one major purpose, and that is to add to the body of knowledge in the field,” said Sy Saeed, MD, MS, chair of the department of psychiatry at East Carolina University, Greenville, N.C., and chair of the group’s administration and leadership committee.

And the organization doesn’t shy from controversial topics, either, such as examining direct-to-consumer marketing and when patients should stop antidepressant therapy.

“We’re very good at getting marketed to on when to start medications, but how good are we at actually timing when to cut back on them? How long is long enough to treat?” Dr. Gross asked. The organization continues to have “an undercurrent of recognizing and fostering change and making people aware of things that may be controversial at times but also further the field by looking at these different areas of psychiatry.”

Despite the group’s relatively small size of about 200 members, its impact touches nearly everyone in the profession, whether they realize it or not. And though the group certainly has its weaknesses – such as steep membership fees that may deter some from joining and its need to improve membership diversity – GAP actively seeks ways to address these internal challenges just as it does external ones.

“It’s probably one of the best-kept secrets in psychiatry,” Dr. Gross said. But it’s a secret the members want out. That’s one reason members consider the organization’s crown jewel to be its fellowship program. In fact, Steven S. Sharfstein, MD, MPA, a former GAP president, clinical professor of psychiatry at the University of Maryland, Baltimore, and chair of the planning, marketing, and communications committee, did not formally join GAP until the 1980s. But he first became involved with the group as a resident in the fellowship program in 1969.

In its current incarnation, 12 fellows spend 2 years as working members of GAP, assigned to one of its committees to put in work just like every other member is expected to do, but they reap the wisdom and mentorship of its members at the same time.

One thing that makes GAP so special to its members is the ability “to mentor young psychiatrists, going from generation to generation trying to identify leaders and facilitate their growth,” Dr. Gross said. And that process, through not only the fellowship program but also through the members’ diversity of ages and career stages, sustains the organization’s vigor.

“Its strength is that you create this continuum where senior people get to mentor people who are early in their career, and this way, the knowledge continues,” Dr. Saaed said.
 

Creation, not death, by committee

In the early years, GAP’s longevity was in question. Once it had successfully steered the APA toward taking more action to address social problems, did it still have a role to play? A majority of members decided that it did. “New problems arose as old ones were solved,” wrote the late Albert Deutsch in an early history of GAP, and “some steps which were confidently expected to repair an ill or defect did not turn out to be completely effective.” In its first decade, GAP members led the APA to establish new medical director and director of information positions, to improve professional standards and facilitate improvement of mental health facilities, and to expand training.

But where GAP really excelled was in developing projects, something the APA wasn’t well-suited to do, explained Carol C. Nadelson, MD, professor of psychiatry at Harvard Medical School, Boston, a member of the gender and mental health committee, and a past president of GAP. And the breadth of those projects has “expanded as the field has changed and evolved,” said Dr. Nadelson, the first woman president of the APA.

Those projects, the beating heart of GAP’s work, come from its specialized working committees, groups of 6-12 members who spend a couple years focused on a single question or problem in psychiatry that the committee has decided needs attention. The number of committees has grown from 9 at its founding to 32 today, shrinking and expanding as society’s needs demand. Each committee looks for an area it thinks is important and needs attention or updating and then decides how to proceed in addressing it. This structure as a confederation of committees differs greatly from other medical organizations.

“Committees really function in an autonomous, almost independent manner,” Dr. Bonner said. “They control their work, what they do, and how they do it, and the executive structure of the organization has very little impact on those individual committees.”

It’s only when a committee produces whatever project it’s working on that it’s disseminated to the rest of the organization for review.

“The fact that it’s such a federated organization is both a strength and a weakness,” said Roberto Lewis-Fernández, MD, professor of clinical psychiatry at Columbia University, New York, and chair of the cultural psychiatry committee. The tension between becoming too siloed within a committee and needing some sense of greater unity and the cross-pollination that provides is always present, but it’s perhaps also part of the organization’s vibrancy as it constantly seeks the right balance.

It also sometimes allows for fruitful collaborations, such as a recent publication produced by both the religion committee and the LGBTQ+ committee on helping LGBTQ+ teenagers and communities of faith, pointed out Jack Drescher, MD, a GAP past president who serves as clinical professor of psychiatry at Columbia University, and a member of the LGBTQ and media committees.

GAP is also unique in expecting every member to actively put in work toward its mission.

“If you join the APA, you can do absolutely nothing, or you can go to a conference once a year and learn from other people, but you don’t have to be active,” said Gail Robinson, MD, professor of psychiatry and ob.gyn. at the University of Toronto and chair of GAP’s gender and mental health committee. But if you’re a GAP member who isn’t contributing, expect to hear from someone asking how they can help you figure out how you can contribute.

Expecting that much work from members means meeting more often than most medical societies. Except during the pandemic, GAP members have always met twice a year for a long weekend in White Plains, N.Y., to focus almost exclusively on the committees’ current projects. Each meeting allows members “to immerse themselves in thinking about topics that the various committees find of interest and think might be of interest to the rest of the world,” said David Adler, MD, a professor of psychiatry and medicine at Tufts Medical Center in Boston, and chair of the GAP publication board. Whereas APA meetings are massive, frenetic events focused primarily on new research and continuing education for tens of thousands of attendees, GAP meetings are more intimidate and meditative, “a time in which the leaders can exchange ideas in a more private setting,” Dr. Adler said.

What makes GAP’s meetings so special is that they provide a temporary refuge with the explicit goal of encouraging unhurried discussion and deliberation about big ideas that matter, Dr. Robinson said.

“One of the enjoyable parts of GAP is that you have time to think,” Dr. Robinson said. “In your regular life, you’re seeing patients, you’re doing research or organizing things, but in GAP, you can sit with a group of like-minded, interested people and toss some ideas around about what’s important right now. What should we be looking at? What is the field not paying enough attention to? And then the ideas bubble up. In a lot of other organizations, you’re doing specific work, some of it political, some in terms of the organization, but to just sort of sit and think about what’s important in your field and what people should know more about is a different kind of feeling.”
 

A force for change

The work GAP produces has had a substantial impact on the field of psychiatry and society in general over the past 7 and a half decades. Consider this list of just a handful of GAP contributions in its first decade.

• Guidance regarding electroconvulsive therapy in 1947, followed by an update, in response to reaction to the first document, in 1950.
• A guide to school integration after Brown v. Board of Education that considered the psychiatric challenges of integration.
• A report for employers on workers with epilepsy for occupational health and safety.
• Publications that raised mental hospital standards in the 1950s.
• A range of action documents used by medical schools, psychology and social work departments and agencies, governmental bodies, courts, industry, public schools, and community health and welfare agencies.

Over the years, GAP’s influence has sometimes been overt – such as publishing the only diagnostic and statistical manual for child psychiatry for years before that material was incorporated into the official DSM. Sometimes it’s just ahead of the curve, such as the women’s mental health committee publishing a paper that reviewed the evidence on “abortion trauma syndrome” and concluding that it doesn’t exist shortly before the American Psychological Association and the U.K.’s Royal College of Psychiatrists published reviews with similar conclusions. In a few instances, GAP has caused shifts in how the APA operates, such as encouraging the larger organization to publish books on mental health, said Dr. Sharfstein, a past president of the APA.

Much of the organization’s impact occurs through its effects on education, which affects clinical psychiatry at large.“Some reports are very much designed to have an impact on psychiatry education, residency training and curriculum development, which would have a big impact on practice,” Dr. Sharfstein said. An example is the committee on disasters, which examines the best ways for mental health professionals to respond to and mitigate the mental health fallout from the consequences of natural and manmade disasters.

Most often, though, GAP’s influence is akin to strategically planting very carefully cultivated seeds throughout the academic and clinical media ecosystems and letting them bloom how they will. For example, Dr. Lewis-Fernández described a project the cultural committee published in 2013: a checklist for how a psychiatry research article should address topics related to race, ethnicity, and culture. After reviewing articles in the field and their methodologies, the group developed a checklist of best practices and tested them with articles in the field to see how the checklist held up before publishing it.

“Initially, some people read it, some people didn’t, but over time, it’s gotten picked up, and it’s now about to be used in a journal on psychiatric services as a guide to authors and reviews on the appropriate use of these concepts,” Dr. Lewis-Fernández said.

GAP’s influence also blooms through the cross-pollination that occurs at meetings, where leaders in psychiatry from all across the country come together, discuss ideas, and then take new ideas back to their universities, where they teach them to their residents. Perhaps the best example of this influence in recent years has been a increasing shift in teaching about LGBTQ+ issues.

“There’s an underrepresentation of teaching about LGBTQ+ issues in many psychiatric training programs in many medical schools,” Dr. Drescher said. The organization has worked to raise awareness about these gaps in the education of medical students and mental health professionals and then address it, such as designing an online module curriculum in the early 2000s for how to teach residents about LGBTQ+ mental health issues and then updating it as needed.

Perhaps GAP’s greatest lifetime achievement is forcing the field of psychiatry to confront the fact that it – and its patients – do not stand apart from the society in which they exist.

“People aren’t just psychiatric disorders. They live in society, and society has an impact on them, and that affects how people cope,” Dr. Robinson said. That was once a radical concept, but now “psychiatry as a whole has moved to be more broadly expansive” just as GAP itself has broadened its scope, as evidenced by the wide range of committees, more than triple what the organization had at its founding. “GAP was really at the vanguard of that expansion into the recognizing the need to consider the interaction between the individual and the environment they live in socially.”

That’s never been more true than during the COVID-19 pandemic, contributing to perhaps the greatest mental health crisis in the nation’s history since World War II. But the pandemic hasn’t slowed down GAP’s work. In fact, in some ways, the pandemic has facilitated the group’s ability to meet more often virtually and focus on acute issues the pandemic itself has caused. The psychopathology committee published one paper on the impact of telehealth on treating the chronic mentally ill during COVID, and another delved into rethinking where things stand with institutional racism within psychiatry. The women’s mental health committee published articles on the impact of COVID on pregnant and postpartum women, and the impact of COVID on minority women.
 

Confronting challenges within, too

For all its positive influence, GAP has its weaknesses as well. Two of the biggest barriers to membership, for example, are the steep dues and travel to the twice annual meetings, Dr. Lewis-Fernández said.

The membership dues are not needlessly high: The organization relies on philanthropy and dues for all of its activities, most recently, secured endowments from institutional and individual donors to fund all of the GAP fellows, Dr. Gross said.

“With a low number of members, the cost is larger per member,” Dr. Bonner explained. In fact, GAP has only recently overcome a period of financial uncertainty, now finally on solid ground in terms of fundings.

While the dues can be onerous, Dr. Lewis-Fernández said the organization has been actively thinking about ways to reduce it, particularly for those who may need help if traveling from farther away or younger-career individuals, such as those without tenure or with young families.

It can also be difficult for the organization to attract diverse members from different racial and ethnic groups when leaders in psychiatry from those backgrounds are courted by many other groups, or just to attract younger members in general, but GAP continues to seek ways to overcome those challenges.

“The majority of people in GAP have some kind of academic interest, and the nature of being an early career psychiatrist in academia is that you have to publish to get promoted,” Dr. Bonner said. GAP’s historical practice of producing publications by committee without individual attribution was a disincentive to those early-career folks. “More recently, we’ve changed that so that now individuals can put their names on their product, which has eliminated that particular barriers for young people.”

As the organization continues to seek ways to address those issues, it also faces the same challenges as every other scientific group: Staying relevant in the new, and constantly changing, media landscape.

“It’s an interesting evolution because it started off with books and monographs for many, many years,” Dr. Robinson said, “and then it kind of moved away from that to more articles.” More recently, some committees have returned to writing books while others explore other forms of media to keep up with the times. Long gone are the days when a committee might spend 2-10 years producing one monograph.

“In today’s world, you can’t be relevant operating that way,” said Dr. Bonner, noting that some committees have produced videos or podcasts.

But the sheer amount of information out there is intimidating as well. “Nowadays, a lot of people get their information off the Internet, and how do you actually sift through that?” Dr. Saeed said. “How you find signal in this noise is a whole different thing now, so how GAP produces its information is at that trajectory right now. Should we be producing more electronic books? What should be our peer-review process? How do we make sure the information is current? If we are about sharing information and generating new knowledge, what’s the best way of disseminating that?”

A testament to the organization’s willingness to confront that challenge, however, is its exploration of every possible platform – even those well outside the traditional ones. The climate committee, for example, recently set about addressing climate anxiety in children, but they didn’t produce a report or develop a teaching module or even develop a series of podcasts. Instead, the committee collaborated with Jeremy D. Wortzel, MPhil, an MD and MPH candidate at the University of Pennsylvania, Philadelphia, and Lena K. Champlin, a doctoral candidate in environmental science at Drexel University, Philadelpha, to write a children’s book. “Coco’s Fire: Changing Climate Anxiety into Climate Action” was published in October 2021.
 

GAP continues to leave its mark

For all the work that members put into the organization, members say they reap substantial benefits as well. Dr. Saaed recalls feeling flattered when invited to join the organization because of how influential it is and the opportunity to work with so many leaders in psychiatry. “When you come to GAP committee meetings, you would run into people whose book or research you might have read and who are very prominent in the field,” he said.

Dr. Drescher credited GAP with helping him develop his voice and polish his editing skills, which later aided him when he became editor of the Journal of Gay and Lesbian Mental Health. When the LGBTQ+ committee shifted from reports to writing op-eds, members learned how to write opinion pieces and then teach members of other committees those skills, resulting in GAP-produced op-eds in consumer and trade publications. And then there are the intangible rewards that leave a profound impact on members.

Some members see GAP as central to their professional lives and perhaps legacies.

“Outside of the medical center, this has probably been the most important professional organization of my career, and I think there are a lot of people who feel that way,” Dr. Adler said. “It’s a very unique experience, and the goal is to examine today’s critical issues and say something about them in a way in which maybe the world will take notice.”

They say you are what you eat, but scientists have long wondered whether breastfeeding babies are what their mothers eat, too. Their question: How much of a nursing mother’s diet eventually plays a role in a child’s food preferences later in life?

The aroma, taste, and makeup of breast milk change from day to day, based mostly on the mother’s diet. But previous research has already shown that the foods a mother eats do not directly translate into the same smells and tastes of that food in breast milk. Some substances from the mother’s diet enter her breast milk, some don’t, and even ones that do may have a different scent or flavor than what the mother experiences.

But a new study suggests that the active ingredient in black pepper makes its way into breast milk and may help the infant develop a tolerance to pepper later. The researchers published their findings in the journal Molecular Nutrition & Food Research.
 

Pinch of pepper

The study authors thought that maybe some food preferences could result from sensory programming that occurs through breast milk in the first few months of life. Though past studies have looked at which odor-producing substances transfer into breast milk, not many have explored specific substances that give food its distinctive flavor, or even what makes up the taste of breast milk. So they decided to investigate what happens when a mother consumes a meal containing three specific compounds: those that give pepper, chili, and ginger their particularly pungent flavors.

The researchers recruited 18 healthy, nonsmoking, nursing mothers who were producing more than enough milk for their baby’s needs. Their breastfeeding children ranged in age from 8 weeks to 1 year old. The women all ate a curry dish after having spent 2 days avoiding onion, garlic, and the spices in the curry. Then they provided pumped breast milk samples at 1, 2, and 3 hours after eating the curry.

Within an hour of the women eating the curry, the scientists were able to detect piperine, the compound that gives black pepper its bite, in the mothers’ breast milk. They did not find the compounds from ginger, chili, or curcumin – the main active ingredient in turmeric – in the breast milk. The piperine remained there for several hours, but there wasn’t enough for an adult to be able to taste it. It wasn’t possible to reliably tell whether the infants could consciously detect the flavor, but the researchers don’t think it’s likely they did.

But the scientists do suggest it’s possible that the piperine in breast milk could regularly activate a protein that detects pungent or potentially harmful substances. This is the same protein that produces the sensation of heat when eating a spicy food. If the piperine frequently activates that protein in a nursing baby at levels too low for the baby to notice, it may increase the baby’s tolerance for similar spicy substances later in life.

Ultimately, the findings suggest that some compounds in a mother’s diet have the potential to influence a child’s taste preferences later.

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

They say you are what you eat, but scientists have long wondered whether breastfeeding babies are what their mothers eat, too. Their question: How much of a nursing mother’s diet eventually plays a role in a child’s food preferences later in life?

The aroma, taste, and makeup of breast milk change from day to day, based mostly on the mother’s diet. But previous research has already shown that the foods a mother eats do not directly translate into the same smells and tastes of that food in breast milk. Some substances from the mother’s diet enter her breast milk, some don’t, and even ones that do may have a different scent or flavor than what the mother experiences.

But a new study suggests that the active ingredient in black pepper makes its way into breast milk and may help the infant develop a tolerance to pepper later. The researchers published their findings in the journal Molecular Nutrition & Food Research.
 

Pinch of pepper

The study authors thought that maybe some food preferences could result from sensory programming that occurs through breast milk in the first few months of life. Though past studies have looked at which odor-producing substances transfer into breast milk, not many have explored specific substances that give food its distinctive flavor, or even what makes up the taste of breast milk. So they decided to investigate what happens when a mother consumes a meal containing three specific compounds: those that give pepper, chili, and ginger their particularly pungent flavors.

The researchers recruited 18 healthy, nonsmoking, nursing mothers who were producing more than enough milk for their baby’s needs. Their breastfeeding children ranged in age from 8 weeks to 1 year old. The women all ate a curry dish after having spent 2 days avoiding onion, garlic, and the spices in the curry. Then they provided pumped breast milk samples at 1, 2, and 3 hours after eating the curry.

Within an hour of the women eating the curry, the scientists were able to detect piperine, the compound that gives black pepper its bite, in the mothers’ breast milk. They did not find the compounds from ginger, chili, or curcumin – the main active ingredient in turmeric – in the breast milk. The piperine remained there for several hours, but there wasn’t enough for an adult to be able to taste it. It wasn’t possible to reliably tell whether the infants could consciously detect the flavor, but the researchers don’t think it’s likely they did.

But the scientists do suggest it’s possible that the piperine in breast milk could regularly activate a protein that detects pungent or potentially harmful substances. This is the same protein that produces the sensation of heat when eating a spicy food. If the piperine frequently activates that protein in a nursing baby at levels too low for the baby to notice, it may increase the baby’s tolerance for similar spicy substances later in life.

Ultimately, the findings suggest that some compounds in a mother’s diet have the potential to influence a child’s taste preferences later.

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

They say you are what you eat, but scientists have long wondered whether breastfeeding babies are what their mothers eat, too. Their question: How much of a nursing mother’s diet eventually plays a role in a child’s food preferences later in life?

The aroma, taste, and makeup of breast milk change from day to day, based mostly on the mother’s diet. But previous research has already shown that the foods a mother eats do not directly translate into the same smells and tastes of that food in breast milk. Some substances from the mother’s diet enter her breast milk, some don’t, and even ones that do may have a different scent or flavor than what the mother experiences.

But a new study suggests that the active ingredient in black pepper makes its way into breast milk and may help the infant develop a tolerance to pepper later. The researchers published their findings in the journal Molecular Nutrition & Food Research.
 

Pinch of pepper

The study authors thought that maybe some food preferences could result from sensory programming that occurs through breast milk in the first few months of life. Though past studies have looked at which odor-producing substances transfer into breast milk, not many have explored specific substances that give food its distinctive flavor, or even what makes up the taste of breast milk. So they decided to investigate what happens when a mother consumes a meal containing three specific compounds: those that give pepper, chili, and ginger their particularly pungent flavors.

The researchers recruited 18 healthy, nonsmoking, nursing mothers who were producing more than enough milk for their baby’s needs. Their breastfeeding children ranged in age from 8 weeks to 1 year old. The women all ate a curry dish after having spent 2 days avoiding onion, garlic, and the spices in the curry. Then they provided pumped breast milk samples at 1, 2, and 3 hours after eating the curry.

Within an hour of the women eating the curry, the scientists were able to detect piperine, the compound that gives black pepper its bite, in the mothers’ breast milk. They did not find the compounds from ginger, chili, or curcumin – the main active ingredient in turmeric – in the breast milk. The piperine remained there for several hours, but there wasn’t enough for an adult to be able to taste it. It wasn’t possible to reliably tell whether the infants could consciously detect the flavor, but the researchers don’t think it’s likely they did.

But the scientists do suggest it’s possible that the piperine in breast milk could regularly activate a protein that detects pungent or potentially harmful substances. This is the same protein that produces the sensation of heat when eating a spicy food. If the piperine frequently activates that protein in a nursing baby at levels too low for the baby to notice, it may increase the baby’s tolerance for similar spicy substances later in life.

Ultimately, the findings suggest that some compounds in a mother’s diet have the potential to influence a child’s taste preferences later.

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

Patients with giant cell arteritis (GCA) remained in remission longer when they took secukinumab (Cosentyx) during a 6-month–long taper of glucocorticoids, a monoclonal antibody drug that inhibits interleukin-17A, compared with placebo, according to phase 2 trial results presented at the virtual annual meeting of the American College of Rheumatology.

The mainstay of GCA treatment is glucocorticoids, although IL-6 inhibition with tocilizumab (Actemra) has recently become another option, Jens Thiel, MD, vice director of the Clinic for Rheumatology and Clinical Immunology at University Hospital Freiburg (Germany), told attendees.

“Secukinumab has shown significant improvements in the signs and symptoms of IL-17A-driven medical conditions such as psoriasis and psoriatic arthritis, and it has a very favorable long-term safety profile,” Dr. Thiel said. “There is experimental and preclinical data that points toward the role of IL-17A in the pathogenesis of giant cell arteritis, and therefore IL-17A inhibition, blocking vascular inflammation, is potentially a new therapeutic target for GCA.”

Christopher R. Palma, MD, ScM, assistant professor in the division of allergy, immunology, and rheumatology at the University of Rochester (N.Y.), said in an interview that the trial’s preliminary findings were exciting because they suggest that IL-17A is likely to be an effective strategy for treating GCA. ”This aligns with known pathophysiology of GCA, where IL-17A is an important part of pathology of disease,” Dr. Palma said.

In the randomized, controlled, double-blind trial, researchers enrolled 52 patients, all at least 50 years old, who had never taken a biologic for GCA. Most of the participants (80.8%) had new-onset GCA, diagnosed within the previous 6 weeks, and 19.2% had relapsing GCA. The participants received either 300 mg of secukinumab or placebo every week for 5 weeks, and then every 4 weeks for 48 total weeks. At baseline, all participants also began a 26-week taper of prednisolone from a dose of 25-60 mg/day at baseline to 0 at week 27. The primary endpoint was the proportion of participants in sustained remission through week 28.

Among the 27 participants taking secukinumab and the 25 taking placebo, 37 completed the study treatment (71%). At week 28, those still in remission included 70.1% of participants taking secukinumab and 20.3% of those taking placebo (odds ratio [OR], 9.3). Through week 52, the proportion of participants in remission included 59.3% of the secukinumab group and 8% of the placebo group.

Determination of flare was based on signs and symptoms along with a C-reactive protein level of more than 10 mg/L or an increased erythrocyte sedimentation rate. Dr. Thiel did not provide more details on these parameters or on how flares were determined, but reported that participants taking secukinumab did not reach a median time to first flare, compared to a median 197 days in the placebo group.

All the participants taking secukinumab and 96% of those taking placebo experienced treatment-emergent adverse events, with serious adverse events occurring in 22.2% of those taking secukinumab and 44% of those taking placebo. Two patients in each group discontinued the treatment because of adverse events, and one participant in each group died from causes determined to be unrelated to the treatment.

The trial’s effect size was large, but Dr. Palma noted that the study’s generalizability is limited by prednisolone tapering in the placebo arm because that’s not reflective of most clinical practice for treatment of GCA.

“We would be unlikely to mimic this trial design as we know rates of disease flare and recurrence are high without long-term therapy of some kind,” Dr. Palma said. ”The real challenge will be in assessing relative benefit and risk among many possible therapies and how IL-17A–directed therapies fit in. Obviously, a head-to-head trial design would help answer many of these questions.”

Dr. Palma said it’s too early to recommend widespread off-label use of secukinumab for GCA, but he would encourage his patients with GCA to consider participating in a phase 3 trial of the drug.

Novartis, which markets secukinumab, funded the research. Dr. Thiel has received speaking and/or advising fees from AbbVie, Bristol-Myers Squibb, GlaxoSmithKline, and Novartis, and research grants from Bristol-Myers Squibb and Novartis. His coauthors had disclosures for a wide range of pharmaceutical companies. Dr. Palma has received research funding from AbbVie, Incyte, and Regeneron.

Patients with giant cell arteritis (GCA) remained in remission longer when they took secukinumab (Cosentyx) during a 6-month–long taper of glucocorticoids, a monoclonal antibody drug that inhibits interleukin-17A, compared with placebo, according to phase 2 trial results presented at the virtual annual meeting of the American College of Rheumatology.

The mainstay of GCA treatment is glucocorticoids, although IL-6 inhibition with tocilizumab (Actemra) has recently become another option, Jens Thiel, MD, vice director of the Clinic for Rheumatology and Clinical Immunology at University Hospital Freiburg (Germany), told attendees.

“Secukinumab has shown significant improvements in the signs and symptoms of IL-17A-driven medical conditions such as psoriasis and psoriatic arthritis, and it has a very favorable long-term safety profile,” Dr. Thiel said. “There is experimental and preclinical data that points toward the role of IL-17A in the pathogenesis of giant cell arteritis, and therefore IL-17A inhibition, blocking vascular inflammation, is potentially a new therapeutic target for GCA.”

Christopher R. Palma, MD, ScM, assistant professor in the division of allergy, immunology, and rheumatology at the University of Rochester (N.Y.), said in an interview that the trial’s preliminary findings were exciting because they suggest that IL-17A is likely to be an effective strategy for treating GCA. ”This aligns with known pathophysiology of GCA, where IL-17A is an important part of pathology of disease,” Dr. Palma said.

In the randomized, controlled, double-blind trial, researchers enrolled 52 patients, all at least 50 years old, who had never taken a biologic for GCA. Most of the participants (80.8%) had new-onset GCA, diagnosed within the previous 6 weeks, and 19.2% had relapsing GCA. The participants received either 300 mg of secukinumab or placebo every week for 5 weeks, and then every 4 weeks for 48 total weeks. At baseline, all participants also began a 26-week taper of prednisolone from a dose of 25-60 mg/day at baseline to 0 at week 27. The primary endpoint was the proportion of participants in sustained remission through week 28.

Among the 27 participants taking secukinumab and the 25 taking placebo, 37 completed the study treatment (71%). At week 28, those still in remission included 70.1% of participants taking secukinumab and 20.3% of those taking placebo (odds ratio [OR], 9.3). Through week 52, the proportion of participants in remission included 59.3% of the secukinumab group and 8% of the placebo group.

Determination of flare was based on signs and symptoms along with a C-reactive protein level of more than 10 mg/L or an increased erythrocyte sedimentation rate. Dr. Thiel did not provide more details on these parameters or on how flares were determined, but reported that participants taking secukinumab did not reach a median time to first flare, compared to a median 197 days in the placebo group.

All the participants taking secukinumab and 96% of those taking placebo experienced treatment-emergent adverse events, with serious adverse events occurring in 22.2% of those taking secukinumab and 44% of those taking placebo. Two patients in each group discontinued the treatment because of adverse events, and one participant in each group died from causes determined to be unrelated to the treatment.

The trial’s effect size was large, but Dr. Palma noted that the study’s generalizability is limited by prednisolone tapering in the placebo arm because that’s not reflective of most clinical practice for treatment of GCA.

“We would be unlikely to mimic this trial design as we know rates of disease flare and recurrence are high without long-term therapy of some kind,” Dr. Palma said. ”The real challenge will be in assessing relative benefit and risk among many possible therapies and how IL-17A–directed therapies fit in. Obviously, a head-to-head trial design would help answer many of these questions.”

Dr. Palma said it’s too early to recommend widespread off-label use of secukinumab for GCA, but he would encourage his patients with GCA to consider participating in a phase 3 trial of the drug.

Novartis, which markets secukinumab, funded the research. Dr. Thiel has received speaking and/or advising fees from AbbVie, Bristol-Myers Squibb, GlaxoSmithKline, and Novartis, and research grants from Bristol-Myers Squibb and Novartis. His coauthors had disclosures for a wide range of pharmaceutical companies. Dr. Palma has received research funding from AbbVie, Incyte, and Regeneron.

Patients with giant cell arteritis (GCA) remained in remission longer when they took secukinumab (Cosentyx) during a 6-month–long taper of glucocorticoids, a monoclonal antibody drug that inhibits interleukin-17A, compared with placebo, according to phase 2 trial results presented at the virtual annual meeting of the American College of Rheumatology.

The mainstay of GCA treatment is glucocorticoids, although IL-6 inhibition with tocilizumab (Actemra) has recently become another option, Jens Thiel, MD, vice director of the Clinic for Rheumatology and Clinical Immunology at University Hospital Freiburg (Germany), told attendees.

“Secukinumab has shown significant improvements in the signs and symptoms of IL-17A-driven medical conditions such as psoriasis and psoriatic arthritis, and it has a very favorable long-term safety profile,” Dr. Thiel said. “There is experimental and preclinical data that points toward the role of IL-17A in the pathogenesis of giant cell arteritis, and therefore IL-17A inhibition, blocking vascular inflammation, is potentially a new therapeutic target for GCA.”

Christopher R. Palma, MD, ScM, assistant professor in the division of allergy, immunology, and rheumatology at the University of Rochester (N.Y.), said in an interview that the trial’s preliminary findings were exciting because they suggest that IL-17A is likely to be an effective strategy for treating GCA. ”This aligns with known pathophysiology of GCA, where IL-17A is an important part of pathology of disease,” Dr. Palma said.

In the randomized, controlled, double-blind trial, researchers enrolled 52 patients, all at least 50 years old, who had never taken a biologic for GCA. Most of the participants (80.8%) had new-onset GCA, diagnosed within the previous 6 weeks, and 19.2% had relapsing GCA. The participants received either 300 mg of secukinumab or placebo every week for 5 weeks, and then every 4 weeks for 48 total weeks. At baseline, all participants also began a 26-week taper of prednisolone from a dose of 25-60 mg/day at baseline to 0 at week 27. The primary endpoint was the proportion of participants in sustained remission through week 28.

Among the 27 participants taking secukinumab and the 25 taking placebo, 37 completed the study treatment (71%). At week 28, those still in remission included 70.1% of participants taking secukinumab and 20.3% of those taking placebo (odds ratio [OR], 9.3). Through week 52, the proportion of participants in remission included 59.3% of the secukinumab group and 8% of the placebo group.

Determination of flare was based on signs and symptoms along with a C-reactive protein level of more than 10 mg/L or an increased erythrocyte sedimentation rate. Dr. Thiel did not provide more details on these parameters or on how flares were determined, but reported that participants taking secukinumab did not reach a median time to first flare, compared to a median 197 days in the placebo group.

All the participants taking secukinumab and 96% of those taking placebo experienced treatment-emergent adverse events, with serious adverse events occurring in 22.2% of those taking secukinumab and 44% of those taking placebo. Two patients in each group discontinued the treatment because of adverse events, and one participant in each group died from causes determined to be unrelated to the treatment.

The trial’s effect size was large, but Dr. Palma noted that the study’s generalizability is limited by prednisolone tapering in the placebo arm because that’s not reflective of most clinical practice for treatment of GCA.

“We would be unlikely to mimic this trial design as we know rates of disease flare and recurrence are high without long-term therapy of some kind,” Dr. Palma said. ”The real challenge will be in assessing relative benefit and risk among many possible therapies and how IL-17A–directed therapies fit in. Obviously, a head-to-head trial design would help answer many of these questions.”

Dr. Palma said it’s too early to recommend widespread off-label use of secukinumab for GCA, but he would encourage his patients with GCA to consider participating in a phase 3 trial of the drug.

Novartis, which markets secukinumab, funded the research. Dr. Thiel has received speaking and/or advising fees from AbbVie, Bristol-Myers Squibb, GlaxoSmithKline, and Novartis, and research grants from Bristol-Myers Squibb and Novartis. His coauthors had disclosures for a wide range of pharmaceutical companies. Dr. Palma has received research funding from AbbVie, Incyte, and Regeneron.

The rate of U.S. hospitalizations for three types of serious infections in patients with psoriatic arthritis (PsA) appears to have declined from 2012 to 2017, according to research presented at the virtual annual meeting of the American College of Rheumatology.

Several of the standard treatments for PsA have an increased risk of infections, but the rates vary amongst conventional disease-modifying antirheumatic drugs (DMARDs), glucocorticoids, biologics, and other therapies.

“Given the uptake of biological therapies has increased over recent years, we sought to investigate the national trends in serious infections in patients with psoriatic arthritis from the years 2012 to 2017,” Vagishwari Murugesan, MBBS, a psoriatic arthritis clinical fellow at the University of Toronto, told attendees in a prerecorded poster presentation. Dr. Murugesan was a fellow at Boston University when she conducted the research.

The researchers analyzed data from 2012 to 2017 in the U.S. National Inpatient Sample (NIS), which includes approximately 20% of all discharges from U.S. community hospitals except rehabilitation and long-term acute care institutions. Using ICD-9 and ICD-10 codes, the researchers identified all discharge records containing a diagnosis of PsA as well as pneumonia, sepsis, urinary tract infection (UTI), and skin and soft-tissue infections. After making adjustments to match U.S. population age distributions over the years, they examined trends in serious infections among patients with PsA for that 6-year period.

Demographics over those years changed little: The average age of discharged patients was 59.5 in 2012 and 60.8 in 2017. Similarly, the patient population was 56% women and 88.5% Whites in 2012 and 57.7% women and 88.4% Whites in 2017. The average length of stay was also similar: 4.7 days in 2012, compared with 4.9 days in 2017.

Among 50,700 discharges of patients with PsA in 2012, the researchers identified 125 with pneumonia, 230 with sepsis, 312 with skin and soft-tissue infections, and 174 with a UTI. Among the 179,400 discharges in 2017 of patients with PsA, 344 had pneumonia, 374 had sepsis, 681 had skin and soft-tissue infections, and 348 had a UTI. After statistical analysis, the researchers found no significant differences in pneumonia diagnoses during the years studied, but they did find a statistically significant decline in sepsis, skin and soft tissue infections, and UTI discharges (P < .001).

A notable limitation of the study is the NIS database’s lack of data on treatments or outpatient data, making it impossible to determine if more infections were occurring but simply being treated in outpatient settings, although it’s not clear why such a substantial shift would occur in just 5 years. It’s also possible that coding practices differ across hospital, but, presumably, the ways they might differ in 2012 would be similar to any differences in 2017.

Bruce Jancin/MDedge News

Arthur Kavanaugh, MD, a professor of medicine and director of the Center for Innovative Therapy at the University of California, San Diego, found the results interesting for what he considers an important topic.

“What makes these data interesting is the same thing that limits their reliability: The authors note that infections decreased ‘despite the increase in use of biologics over this time,’ ” Dr. Kavanaugh said in an interview. “These are claims data, so there is no way to support any association between those serious infections and biologic use. Indeed, multiple factors could have also impacted these data. It is not possible to tell from claims data.”

Dr. Kavanaugh said the question is worth investigating further with data from other sources.

The research was funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. One study coauthor reported ties to UCB; Dr. Murugesan and her other coauthors reported no disclosures. Dr. Kavanaugh had no disclosures.

The rate of U.S. hospitalizations for three types of serious infections in patients with psoriatic arthritis (PsA) appears to have declined from 2012 to 2017, according to research presented at the virtual annual meeting of the American College of Rheumatology.

Several of the standard treatments for PsA have an increased risk of infections, but the rates vary amongst conventional disease-modifying antirheumatic drugs (DMARDs), glucocorticoids, biologics, and other therapies.

“Given the uptake of biological therapies has increased over recent years, we sought to investigate the national trends in serious infections in patients with psoriatic arthritis from the years 2012 to 2017,” Vagishwari Murugesan, MBBS, a psoriatic arthritis clinical fellow at the University of Toronto, told attendees in a prerecorded poster presentation. Dr. Murugesan was a fellow at Boston University when she conducted the research.

The researchers analyzed data from 2012 to 2017 in the U.S. National Inpatient Sample (NIS), which includes approximately 20% of all discharges from U.S. community hospitals except rehabilitation and long-term acute care institutions. Using ICD-9 and ICD-10 codes, the researchers identified all discharge records containing a diagnosis of PsA as well as pneumonia, sepsis, urinary tract infection (UTI), and skin and soft-tissue infections. After making adjustments to match U.S. population age distributions over the years, they examined trends in serious infections among patients with PsA for that 6-year period.

Demographics over those years changed little: The average age of discharged patients was 59.5 in 2012 and 60.8 in 2017. Similarly, the patient population was 56% women and 88.5% Whites in 2012 and 57.7% women and 88.4% Whites in 2017. The average length of stay was also similar: 4.7 days in 2012, compared with 4.9 days in 2017.

Among 50,700 discharges of patients with PsA in 2012, the researchers identified 125 with pneumonia, 230 with sepsis, 312 with skin and soft-tissue infections, and 174 with a UTI. Among the 179,400 discharges in 2017 of patients with PsA, 344 had pneumonia, 374 had sepsis, 681 had skin and soft-tissue infections, and 348 had a UTI. After statistical analysis, the researchers found no significant differences in pneumonia diagnoses during the years studied, but they did find a statistically significant decline in sepsis, skin and soft tissue infections, and UTI discharges (P < .001).

A notable limitation of the study is the NIS database’s lack of data on treatments or outpatient data, making it impossible to determine if more infections were occurring but simply being treated in outpatient settings, although it’s not clear why such a substantial shift would occur in just 5 years. It’s also possible that coding practices differ across hospital, but, presumably, the ways they might differ in 2012 would be similar to any differences in 2017.

Bruce Jancin/MDedge News

Arthur Kavanaugh, MD, a professor of medicine and director of the Center for Innovative Therapy at the University of California, San Diego, found the results interesting for what he considers an important topic.

“What makes these data interesting is the same thing that limits their reliability: The authors note that infections decreased ‘despite the increase in use of biologics over this time,’ ” Dr. Kavanaugh said in an interview. “These are claims data, so there is no way to support any association between those serious infections and biologic use. Indeed, multiple factors could have also impacted these data. It is not possible to tell from claims data.”

Dr. Kavanaugh said the question is worth investigating further with data from other sources.

The research was funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. One study coauthor reported ties to UCB; Dr. Murugesan and her other coauthors reported no disclosures. Dr. Kavanaugh had no disclosures.

The rate of U.S. hospitalizations for three types of serious infections in patients with psoriatic arthritis (PsA) appears to have declined from 2012 to 2017, according to research presented at the virtual annual meeting of the American College of Rheumatology.

Several of the standard treatments for PsA have an increased risk of infections, but the rates vary amongst conventional disease-modifying antirheumatic drugs (DMARDs), glucocorticoids, biologics, and other therapies.

“Given the uptake of biological therapies has increased over recent years, we sought to investigate the national trends in serious infections in patients with psoriatic arthritis from the years 2012 to 2017,” Vagishwari Murugesan, MBBS, a psoriatic arthritis clinical fellow at the University of Toronto, told attendees in a prerecorded poster presentation. Dr. Murugesan was a fellow at Boston University when she conducted the research.

The researchers analyzed data from 2012 to 2017 in the U.S. National Inpatient Sample (NIS), which includes approximately 20% of all discharges from U.S. community hospitals except rehabilitation and long-term acute care institutions. Using ICD-9 and ICD-10 codes, the researchers identified all discharge records containing a diagnosis of PsA as well as pneumonia, sepsis, urinary tract infection (UTI), and skin and soft-tissue infections. After making adjustments to match U.S. population age distributions over the years, they examined trends in serious infections among patients with PsA for that 6-year period.

Demographics over those years changed little: The average age of discharged patients was 59.5 in 2012 and 60.8 in 2017. Similarly, the patient population was 56% women and 88.5% Whites in 2012 and 57.7% women and 88.4% Whites in 2017. The average length of stay was also similar: 4.7 days in 2012, compared with 4.9 days in 2017.

Among 50,700 discharges of patients with PsA in 2012, the researchers identified 125 with pneumonia, 230 with sepsis, 312 with skin and soft-tissue infections, and 174 with a UTI. Among the 179,400 discharges in 2017 of patients with PsA, 344 had pneumonia, 374 had sepsis, 681 had skin and soft-tissue infections, and 348 had a UTI. After statistical analysis, the researchers found no significant differences in pneumonia diagnoses during the years studied, but they did find a statistically significant decline in sepsis, skin and soft tissue infections, and UTI discharges (P < .001).

A notable limitation of the study is the NIS database’s lack of data on treatments or outpatient data, making it impossible to determine if more infections were occurring but simply being treated in outpatient settings, although it’s not clear why such a substantial shift would occur in just 5 years. It’s also possible that coding practices differ across hospital, but, presumably, the ways they might differ in 2012 would be similar to any differences in 2017.

Bruce Jancin/MDedge News

Arthur Kavanaugh, MD, a professor of medicine and director of the Center for Innovative Therapy at the University of California, San Diego, found the results interesting for what he considers an important topic.

“What makes these data interesting is the same thing that limits their reliability: The authors note that infections decreased ‘despite the increase in use of biologics over this time,’ ” Dr. Kavanaugh said in an interview. “These are claims data, so there is no way to support any association between those serious infections and biologic use. Indeed, multiple factors could have also impacted these data. It is not possible to tell from claims data.”

Dr. Kavanaugh said the question is worth investigating further with data from other sources.

The research was funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. One study coauthor reported ties to UCB; Dr. Murugesan and her other coauthors reported no disclosures. Dr. Kavanaugh had no disclosures.

Each month of glucocorticoid use in middle-aged patients with rheumatoid arthritis increases their odds of a major adverse cardiac event by 14%, independent of their baseline cardiovascular risk, according to a Veterans Administration study presented at the virtual annual meeting of the American College of Rheumatology. A similar study of Medicare and insurance claims data also presented at the meeting similarly found a dose-dependent increase in cardiovascular risk with long-term glucocorticoid use among patients with RA.

Up to half of patients with RA use long-term glucocorticoids, Beth Wallace, MD, an assistant professor of internal medicine at the University of Michigan, Ann Arbor, and a staff rheumatologist at the VA Ann Arbor Healthcare Center, told attendees in her presentation.

“Despite previous work suggesting they increase major [adverse] cardiovascular events, or MACE, in a dose-dependent way, prior work suggests long-term glucocorticoid use is common among RA patients with traditional basic risk factors like hyperlipidemia, diabetes, hypertension, and smoking,” Dr. Wallace said. “But we know little about the incremental effects of ongoing glucocorticoid use on MACE risk in RA, particularly as traditional predisposing comorbidities might confound its assessment.”

VA study details

The retrospective cohort study relied on VA administrative data for 26,239 patients with RA who had at least one rheumatology visit during 2013-2017. Only adults aged 40-90 were included (85% men), and none had other rheumatologic conditions, a previous MACE, or congestive heart failure in the preceding 5 years.

The researchers used pharmacy dispensing data to determine exposure to glucocorticoids, based on the number of days’ supply per 6 months and claims data to identify the primary outcome of MACE, defined as acute myocardial infarction, stroke, transient ischemic attack, cardiac arrest, or coronary revascularization, in the following 6 months. After a first MACE, a patient was removed from subsequent analysis so that only a participant’s initial event was considered.

The researchers adjusted their analysis for demographics, health care utilization, long-term glucocorticoid use (over 90 days), use of methotrexate or biologics, and baseline cardiac risk based on the Veterans Affairs Risk Score for Cardiovascular Disease (VARS-CVD). The VARS-CVD uses age, sex, race, tobacco use, systolic blood pressure, cholesterol, diabetes diagnosis, and use of antihypertensives to estimate the risk of a MACE in the next 5 years. A 5-year risk of less than 3% was considered low, 3%-9% medium, and above 9% high.

The population’s median 5-year MACE risk based on VARS-CVD was 5.7%, with nearly a quarter of participants (23%) having a high risk. During the first year of follow-up, 23% of patients overall, including 24% of those with high risk, received at least 90 days of glucocorticoids. An incident MACE occurred in 3.2% of overall patients and in 4.9% of high-risk patients. Median time until an incident MACE was 25 months.

After adjusting for confounders, the researchers calculated that each additional 30 days of glucocorticoid use per 6-month period was linked to a 14% increase in odds of a MACE in the subsequent 6-month period (odds ratio, 1.14). This finding remained independent of baseline cardiovascular risk, previous long-term exposure to glucocorticoids, baseline office visits, methotrexate or biologic use, and baseline Elixhauser Cormobidity Index (except rheumatoid arthritis, diabetes, hypertension, and congestive heart failure).

Dr. Wallace noted that the observational study could still include residual confounding because of factors such as rheumatic disease activity, glucocorticoid dose, and care outside the VA. They also did not distinguish between existing and incident RA and were missing some VARS-CVD data, and they did not adjust for hydroxychloroquine use, which can reduce cardiovascular risk.
 

Details of Medicare and private insurance claims study

In the second study, Brian Coburn, MD, a fourth-year internal medicine resident at the University of Pennsylvania, Philadelphia, presented findings on long-term glucocorticoid use and cardiovascular outcomes in patients with RA based on 2006-2015 claims data from Medicare and the Optum Clinformatics Data Mart. That study similarly found a dose-dependent increase in cardiovascular risk with increasing dosage of long-term glucocorticoids.

All the patients in the two databases had an RA diagnosis and remained on disease-modifying antirheumatic drugs (DMARDs) for at least 180 days without adding a new DMARD or stopping therapy for more than 90 days. Patients were not included if they had a history of myocardial infarction, stroke, coronary artery bypass grafting, or percutaneous coronary intervention.

Using the 180 days before and after starting DMARDs as baseline, the researchers assessed average dose of glucocorticoids during the last 90 days of the baseline period. Participants included 135,583 patients with Medicare, contributing 158,839 years at risk, and 39,272 patients in the Optum database, contributing 36,876 years at risk. The researchers then assessed composite cardiovascular events as a combination of strokes and myocardial infarctions.

A total of 2,067 cardiovascular events occurred among the Medicare patients, for a incidence of 1.3 events per 100 people per year, and 313 cardiovascular events occurred among Optum patients, for an incidence of 0.8 events per 100 people per year.

Over 1 year, a predicted 1.1% of Medicare patients not taking glucocorticoids would experience a stroke or heart attack, compared with 1.4% of those taking up to 5 mg/day of glucocorticoids, 1.7% of those taking 5-10 mg/day glucocorticoids, and 1.9% of those taking more than 10 mg/day glucocorticoids. The number needed to harm was 400 people for up to 5 mg/day, 192 people for 5-10 mg/day, and 137 people for more than 10 mg/day.

Among Optum patients, 0.7% not taking glucocorticoids would experience a stroke or heart attack over 1 year, compared with 0.9% of those taking up to 5 mg/day and 0.8% of those taking either 5-10 mg/day or more than 10 mg/day. The number needed to harm was 714 people for up to 5 mg/day of glucocorticoids, 5,000 people for 5-10 mg/day, and 1,667 for over 10 mg/day.

Dr. Bartels noted that this study “reported unadjusted rates, without controlling for traditional CVD risk factors, for instance, so it will be interesting to see that report after full analysis and peer review as well.” She added that the rates in the VA study may even be higher if there were uncounted cardiovascular events or deaths outside the VA.

“The key take away is that glucocorticoids have dose-related cardiovascular risk shown in both duration and dose of use now in these three large U.S. cohorts,” Dr. Bartels said. “Providers need to counsel patients in judicious use of glucocorticoids, favoring the role of biologic and nonbiologic DMARDs while balancing unique needs and quality-of-life considerations in our patients.”

The VA retrospective cohort study was funded by the National Institutes of Health, the American Autoimmune Related Diseases Association, the U.S. Department of Veterans Affairs, and the Michigan Institute for Clinical & Health Research. Dr. Wallace and seven other authors reported no disclosures. Several coauthors reported financial ties to multiple pharmaceutical companies. The Medicare/Optum retrospective cohort study was funded by the National Institutes of Health, the Patient-Centered Outcomes Research Institute, and the Rheumatology Research Foundation. Dr. Coburn and five coauthors had no disclosures, while several others reported financial ties to a variety of pharmaceutical companies. Dr. Bartels has received institutional grant support from Pfizer for tobacco cessation research

Each month of glucocorticoid use in middle-aged patients with rheumatoid arthritis increases their odds of a major adverse cardiac event by 14%, independent of their baseline cardiovascular risk, according to a Veterans Administration study presented at the virtual annual meeting of the American College of Rheumatology. A similar study of Medicare and insurance claims data also presented at the meeting similarly found a dose-dependent increase in cardiovascular risk with long-term glucocorticoid use among patients with RA.

Up to half of patients with RA use long-term glucocorticoids, Beth Wallace, MD, an assistant professor of internal medicine at the University of Michigan, Ann Arbor, and a staff rheumatologist at the VA Ann Arbor Healthcare Center, told attendees in her presentation.

“Despite previous work suggesting they increase major [adverse] cardiovascular events, or MACE, in a dose-dependent way, prior work suggests long-term glucocorticoid use is common among RA patients with traditional basic risk factors like hyperlipidemia, diabetes, hypertension, and smoking,” Dr. Wallace said. “But we know little about the incremental effects of ongoing glucocorticoid use on MACE risk in RA, particularly as traditional predisposing comorbidities might confound its assessment.”

VA study details

The retrospective cohort study relied on VA administrative data for 26,239 patients with RA who had at least one rheumatology visit during 2013-2017. Only adults aged 40-90 were included (85% men), and none had other rheumatologic conditions, a previous MACE, or congestive heart failure in the preceding 5 years.

The researchers used pharmacy dispensing data to determine exposure to glucocorticoids, based on the number of days’ supply per 6 months and claims data to identify the primary outcome of MACE, defined as acute myocardial infarction, stroke, transient ischemic attack, cardiac arrest, or coronary revascularization, in the following 6 months. After a first MACE, a patient was removed from subsequent analysis so that only a participant’s initial event was considered.

The researchers adjusted their analysis for demographics, health care utilization, long-term glucocorticoid use (over 90 days), use of methotrexate or biologics, and baseline cardiac risk based on the Veterans Affairs Risk Score for Cardiovascular Disease (VARS-CVD). The VARS-CVD uses age, sex, race, tobacco use, systolic blood pressure, cholesterol, diabetes diagnosis, and use of antihypertensives to estimate the risk of a MACE in the next 5 years. A 5-year risk of less than 3% was considered low, 3%-9% medium, and above 9% high.

The population’s median 5-year MACE risk based on VARS-CVD was 5.7%, with nearly a quarter of participants (23%) having a high risk. During the first year of follow-up, 23% of patients overall, including 24% of those with high risk, received at least 90 days of glucocorticoids. An incident MACE occurred in 3.2% of overall patients and in 4.9% of high-risk patients. Median time until an incident MACE was 25 months.

After adjusting for confounders, the researchers calculated that each additional 30 days of glucocorticoid use per 6-month period was linked to a 14% increase in odds of a MACE in the subsequent 6-month period (odds ratio, 1.14). This finding remained independent of baseline cardiovascular risk, previous long-term exposure to glucocorticoids, baseline office visits, methotrexate or biologic use, and baseline Elixhauser Cormobidity Index (except rheumatoid arthritis, diabetes, hypertension, and congestive heart failure).

Dr. Wallace noted that the observational study could still include residual confounding because of factors such as rheumatic disease activity, glucocorticoid dose, and care outside the VA. They also did not distinguish between existing and incident RA and were missing some VARS-CVD data, and they did not adjust for hydroxychloroquine use, which can reduce cardiovascular risk.
 

Details of Medicare and private insurance claims study

In the second study, Brian Coburn, MD, a fourth-year internal medicine resident at the University of Pennsylvania, Philadelphia, presented findings on long-term glucocorticoid use and cardiovascular outcomes in patients with RA based on 2006-2015 claims data from Medicare and the Optum Clinformatics Data Mart. That study similarly found a dose-dependent increase in cardiovascular risk with increasing dosage of long-term glucocorticoids.

All the patients in the two databases had an RA diagnosis and remained on disease-modifying antirheumatic drugs (DMARDs) for at least 180 days without adding a new DMARD or stopping therapy for more than 90 days. Patients were not included if they had a history of myocardial infarction, stroke, coronary artery bypass grafting, or percutaneous coronary intervention.

Using the 180 days before and after starting DMARDs as baseline, the researchers assessed average dose of glucocorticoids during the last 90 days of the baseline period. Participants included 135,583 patients with Medicare, contributing 158,839 years at risk, and 39,272 patients in the Optum database, contributing 36,876 years at risk. The researchers then assessed composite cardiovascular events as a combination of strokes and myocardial infarctions.

A total of 2,067 cardiovascular events occurred among the Medicare patients, for a incidence of 1.3 events per 100 people per year, and 313 cardiovascular events occurred among Optum patients, for an incidence of 0.8 events per 100 people per year.

Over 1 year, a predicted 1.1% of Medicare patients not taking glucocorticoids would experience a stroke or heart attack, compared with 1.4% of those taking up to 5 mg/day of glucocorticoids, 1.7% of those taking 5-10 mg/day glucocorticoids, and 1.9% of those taking more than 10 mg/day glucocorticoids. The number needed to harm was 400 people for up to 5 mg/day, 192 people for 5-10 mg/day, and 137 people for more than 10 mg/day.

Among Optum patients, 0.7% not taking glucocorticoids would experience a stroke or heart attack over 1 year, compared with 0.9% of those taking up to 5 mg/day and 0.8% of those taking either 5-10 mg/day or more than 10 mg/day. The number needed to harm was 714 people for up to 5 mg/day of glucocorticoids, 5,000 people for 5-10 mg/day, and 1,667 for over 10 mg/day.

Dr. Bartels noted that this study “reported unadjusted rates, without controlling for traditional CVD risk factors, for instance, so it will be interesting to see that report after full analysis and peer review as well.” She added that the rates in the VA study may even be higher if there were uncounted cardiovascular events or deaths outside the VA.

“The key take away is that glucocorticoids have dose-related cardiovascular risk shown in both duration and dose of use now in these three large U.S. cohorts,” Dr. Bartels said. “Providers need to counsel patients in judicious use of glucocorticoids, favoring the role of biologic and nonbiologic DMARDs while balancing unique needs and quality-of-life considerations in our patients.”

The VA retrospective cohort study was funded by the National Institutes of Health, the American Autoimmune Related Diseases Association, the U.S. Department of Veterans Affairs, and the Michigan Institute for Clinical & Health Research. Dr. Wallace and seven other authors reported no disclosures. Several coauthors reported financial ties to multiple pharmaceutical companies. The Medicare/Optum retrospective cohort study was funded by the National Institutes of Health, the Patient-Centered Outcomes Research Institute, and the Rheumatology Research Foundation. Dr. Coburn and five coauthors had no disclosures, while several others reported financial ties to a variety of pharmaceutical companies. Dr. Bartels has received institutional grant support from Pfizer for tobacco cessation research

Each month of glucocorticoid use in middle-aged patients with rheumatoid arthritis increases their odds of a major adverse cardiac event by 14%, independent of their baseline cardiovascular risk, according to a Veterans Administration study presented at the virtual annual meeting of the American College of Rheumatology. A similar study of Medicare and insurance claims data also presented at the meeting similarly found a dose-dependent increase in cardiovascular risk with long-term glucocorticoid use among patients with RA.

Up to half of patients with RA use long-term glucocorticoids, Beth Wallace, MD, an assistant professor of internal medicine at the University of Michigan, Ann Arbor, and a staff rheumatologist at the VA Ann Arbor Healthcare Center, told attendees in her presentation.

“Despite previous work suggesting they increase major [adverse] cardiovascular events, or MACE, in a dose-dependent way, prior work suggests long-term glucocorticoid use is common among RA patients with traditional basic risk factors like hyperlipidemia, diabetes, hypertension, and smoking,” Dr. Wallace said. “But we know little about the incremental effects of ongoing glucocorticoid use on MACE risk in RA, particularly as traditional predisposing comorbidities might confound its assessment.”

VA study details

The retrospective cohort study relied on VA administrative data for 26,239 patients with RA who had at least one rheumatology visit during 2013-2017. Only adults aged 40-90 were included (85% men), and none had other rheumatologic conditions, a previous MACE, or congestive heart failure in the preceding 5 years.

The researchers used pharmacy dispensing data to determine exposure to glucocorticoids, based on the number of days’ supply per 6 months and claims data to identify the primary outcome of MACE, defined as acute myocardial infarction, stroke, transient ischemic attack, cardiac arrest, or coronary revascularization, in the following 6 months. After a first MACE, a patient was removed from subsequent analysis so that only a participant’s initial event was considered.

The researchers adjusted their analysis for demographics, health care utilization, long-term glucocorticoid use (over 90 days), use of methotrexate or biologics, and baseline cardiac risk based on the Veterans Affairs Risk Score for Cardiovascular Disease (VARS-CVD). The VARS-CVD uses age, sex, race, tobacco use, systolic blood pressure, cholesterol, diabetes diagnosis, and use of antihypertensives to estimate the risk of a MACE in the next 5 years. A 5-year risk of less than 3% was considered low, 3%-9% medium, and above 9% high.

The population’s median 5-year MACE risk based on VARS-CVD was 5.7%, with nearly a quarter of participants (23%) having a high risk. During the first year of follow-up, 23% of patients overall, including 24% of those with high risk, received at least 90 days of glucocorticoids. An incident MACE occurred in 3.2% of overall patients and in 4.9% of high-risk patients. Median time until an incident MACE was 25 months.

After adjusting for confounders, the researchers calculated that each additional 30 days of glucocorticoid use per 6-month period was linked to a 14% increase in odds of a MACE in the subsequent 6-month period (odds ratio, 1.14). This finding remained independent of baseline cardiovascular risk, previous long-term exposure to glucocorticoids, baseline office visits, methotrexate or biologic use, and baseline Elixhauser Cormobidity Index (except rheumatoid arthritis, diabetes, hypertension, and congestive heart failure).

Dr. Wallace noted that the observational study could still include residual confounding because of factors such as rheumatic disease activity, glucocorticoid dose, and care outside the VA. They also did not distinguish between existing and incident RA and were missing some VARS-CVD data, and they did not adjust for hydroxychloroquine use, which can reduce cardiovascular risk.
 

Details of Medicare and private insurance claims study

In the second study, Brian Coburn, MD, a fourth-year internal medicine resident at the University of Pennsylvania, Philadelphia, presented findings on long-term glucocorticoid use and cardiovascular outcomes in patients with RA based on 2006-2015 claims data from Medicare and the Optum Clinformatics Data Mart. That study similarly found a dose-dependent increase in cardiovascular risk with increasing dosage of long-term glucocorticoids.

All the patients in the two databases had an RA diagnosis and remained on disease-modifying antirheumatic drugs (DMARDs) for at least 180 days without adding a new DMARD or stopping therapy for more than 90 days. Patients were not included if they had a history of myocardial infarction, stroke, coronary artery bypass grafting, or percutaneous coronary intervention.

Using the 180 days before and after starting DMARDs as baseline, the researchers assessed average dose of glucocorticoids during the last 90 days of the baseline period. Participants included 135,583 patients with Medicare, contributing 158,839 years at risk, and 39,272 patients in the Optum database, contributing 36,876 years at risk. The researchers then assessed composite cardiovascular events as a combination of strokes and myocardial infarctions.

A total of 2,067 cardiovascular events occurred among the Medicare patients, for a incidence of 1.3 events per 100 people per year, and 313 cardiovascular events occurred among Optum patients, for an incidence of 0.8 events per 100 people per year.

Over 1 year, a predicted 1.1% of Medicare patients not taking glucocorticoids would experience a stroke or heart attack, compared with 1.4% of those taking up to 5 mg/day of glucocorticoids, 1.7% of those taking 5-10 mg/day glucocorticoids, and 1.9% of those taking more than 10 mg/day glucocorticoids. The number needed to harm was 400 people for up to 5 mg/day, 192 people for 5-10 mg/day, and 137 people for more than 10 mg/day.

Among Optum patients, 0.7% not taking glucocorticoids would experience a stroke or heart attack over 1 year, compared with 0.9% of those taking up to 5 mg/day and 0.8% of those taking either 5-10 mg/day or more than 10 mg/day. The number needed to harm was 714 people for up to 5 mg/day of glucocorticoids, 5,000 people for 5-10 mg/day, and 1,667 for over 10 mg/day.

Dr. Bartels noted that this study “reported unadjusted rates, without controlling for traditional CVD risk factors, for instance, so it will be interesting to see that report after full analysis and peer review as well.” She added that the rates in the VA study may even be higher if there were uncounted cardiovascular events or deaths outside the VA.

“The key take away is that glucocorticoids have dose-related cardiovascular risk shown in both duration and dose of use now in these three large U.S. cohorts,” Dr. Bartels said. “Providers need to counsel patients in judicious use of glucocorticoids, favoring the role of biologic and nonbiologic DMARDs while balancing unique needs and quality-of-life considerations in our patients.”

The VA retrospective cohort study was funded by the National Institutes of Health, the American Autoimmune Related Diseases Association, the U.S. Department of Veterans Affairs, and the Michigan Institute for Clinical & Health Research. Dr. Wallace and seven other authors reported no disclosures. Several coauthors reported financial ties to multiple pharmaceutical companies. The Medicare/Optum retrospective cohort study was funded by the National Institutes of Health, the Patient-Centered Outcomes Research Institute, and the Rheumatology Research Foundation. Dr. Coburn and five coauthors had no disclosures, while several others reported financial ties to a variety of pharmaceutical companies. Dr. Bartels has received institutional grant support from Pfizer for tobacco cessation research