Women's Health

FAIRFAX, VIRGINIA — Pharmacologic treatment of gestational diabetes mellitus (GDM) remains challenged by overall poor trial quality, clinical practice guidelines that offer differing advice, and a limited ability to predict individual risk and treatment response, but researchers at the biennial meeting of the Diabetes in Pregnancy Study Group of North America expressed hope for more clarity in the near future and the ability to someday individualize treatment to account for what is increasingly viewed as a heterogeneous condition.

Until studies in 2015 and 2018 cast doubt on glyburide, “we used to have 80% [of our GDM patients] on glyburide, and 20% on insulin,” Maisa Feghali, MD, of the University of Pittsburgh, said during a discussion period. “Now we have 95% on insulin and 5% on oral hypoglycemics. I rely on insulin because I don’t have a better option, and I rely on research efforts [underway to provide better options]” in the future.

The American College of Obstetricians and Gynecologists recommends insulin as the preferred first-line pharmacologic therapy for GDM when pharmacologic therapy is needed, with metformin as an option when patients decline or cannot safely use insulin. Glyburide, ACOG said in its 2018 practice bulletin on GDM (Obstet Gynecol. 2018;131[2]:e49-64), should not be recommended as a first-line pharmacologic therapy.

The Society of Maternal-Fetal Medicine, on the other hand, has accepted metformin as a “reasonable and safe” first-line alternative to insulin — while recognizing that half of women will still require insulin to achieve glycemic control — and does not rule out consideration of glyburide. In its 2018 statement on the pharmacologic treatment of GDM, the society said that the evidence of benefit of one oral agent over another remains limited.  

“When you have dueling guidelines, it means the data are not that clear,” George Saade, MD, professor and chair of obstetrics and gynecology at the Eastern Virginia School of Medicine, Norfolk, said in a presentation on GDM. An upcoming $12 million multicenter study to be led by the Ohio State University College of Medicine — coined the DECIDE trial — should provide clarity, he said.

The trial, funded by the Patient-Centered Outcomes Research Institute, which funds comparative clinical effectiveness research designed to be broadly applicable to practice, will enroll and randomize over 1500 pregnant individuals with GDM to either oral metformin or insulin and will follow mothers and children until 2 years after delivery.

The study’s primary and secondary hypotheses, respectively, are that metformin is not inferior to insulin in reducing a composite adverse neonatal outcome (large for gestational age, neonatal hypoglycemia and/or hyperbilirubemia) and that metformin does not result in increased child body mass index at 2 years, compared with insulin. It will also look at patient-reported factors associated with metformin use compared to insulin use — factors that “are important ... to enable clinical implementation of study findings,” said Dr. Saade, who played a role in designing the study over the past several years.

The study will take a pragmatic, real-world approach by ensuring racial and ethnic, socioeconomic, urban and rural, and geographic diversity at both large academic and community-based sites across the United States.

The trial, to be led by Mark Landon, MD, and Kartik Venkatesh, MD, PhD, of Ohio State University, will be the first large trial in the United States to both directly compare the ability of oral hypoglycemics and insulin to prevent GDM-associated pregnancy complications, and to follow children for 2 years, Dr. Saade said. “Prior research was either outside the United States, not randomized, not adequately powered, or had no long-term child follow-up,” he added after the meeting.
 

The State Of Knowledge About Oral Hypoglycemics

The trial was envisioned several years ago as a three-arm comparative trial including the sulfonylurea glyburide, but data published in recent years has increasingly “not favored” glyburide, and many providers “have stopped using it,” Dr. Saade said during and after the meeting. At this point, “it would not be useful to include it” in a pragmatic trial, he said.

Glyburide became the number one agent after a seminal trial published in 2000 (N Engl J Med. 2000;343:1134-8) showed equivalent glycemic control in about 400 women with GDM who were randomized to receive insulin or glyburide. While the trial was not powered to evaluate other outcomes, there were no significant differences in neonatal complications.

In 2015, a large retrospective population-based study (JAMA Pediatr. 2015;169[5]:452-8) of more than 9,000 women with GDM showed higher risks of neonatal intensive care admission, neonatal hypoglycemia, and large-for-gestational age with glyburide compared with insulin. “It prompted a pause in thinking,” Dr. Saade recalled at the DPSG meeting. After that, several meta-analyses/systematic reviews compared the two treatments, showing varying and sometimes conflicting degrees of difference in neonatal outcomes.

In 2018, a French noninferiority randomized controlled trial (JAMA 2018;319[17]:1773-80) did not show that glyburide is not inferior to insulin in the prevention of perinatal outcomes (macrosomia, neonatal hypoglycemia, and hyperbilirubinemia). “If you add this trial to the systematic reviews, it would probably would shift more in favor of insulin,” Dr. Saade said, noting that the trial’s supplementary data included a higher rate of maternal hypoglycemia with glyburide. “I feel personally now, with all the data, that glyburide is inferior to insulin.”

A 2021 network meta-analysis (BMC Endocr Disord. 2021;21:199) that looked at glycemic control and neonatal outcomes in GDM treated with glyburide, metformin, or insulin, also offers valuable insight, Dr. Saade said. The meta-analysis used a Bayesian framework and presents results as a ranking estimated probability of a treatment being the best or worst — or in between — for different outcomes (glycemic control and neonatal outcomes), which “is one of the best ways to look at data these days,” he said.

“It tells us how likely [it is for one agent] to be better than others. Will it work most of the time? More than 60% of the time?” Dr. Saade explained. For example, the analysis “tell us that for large for gestational age, glyburide has a 94% chance of being the worst, metformin has an 80% change of being the best, and insulin a 76% chance of being in between.”

Overall, the 2021 analysis suggests that “glyburide is the most likely to be worst in most outcomes and that there is equipoise between metformin and insulin,” he said.

Meta-analyses of pharmacologic treatment of GDM have been challenged, he said, by inconsistent reporting in trials of GDM diagnostic criteria, severity of hyperglycemia, and small sample sizes (and wide confidence intervals). Criteria for supplemental insulin are also often “unclear” in trials, Dr. Saade said, as is involvement of social determinants of health and the “care package” enveloping pharmacologic interventions.

Dr. Saade, Dr. Landon, and other researchers have also lamented over the years that there is limited long-term follow-up of exposed offspring.
 

The Challenge of Heterogeneity

In another presentation on GDM, Maisa Feghali, MD, MS, emphasized that GDM is a heterogeneous condition, with clinical hyperglycemia not capturing individual variation in underlying physiologic processes. A 2016 study (Diabetes Care. 2016;39[6]:1052-5) assessing insulin sensitivity and secretion in 800-plus women at 24-30 weeks’ gestation found that about 50% of those with GDM had predominant insulin resistance, 30% had predominant insulin secretion deficit, and 20% were mixed.

Those with predominant insulin resistance had higher BMI, higher fasting glucose, larger infants, and greater risk of GDM-associated adverse outcomes, “suggesting that the risk is not universal or equivalent,” said Dr. Feghali, assistant professor in the department of obstetrics, gynecology and reproductive sciences at the University of Pittsburgh and the UPCM Magee-Women’s Hospital.

A 2019 multicenter European study (Diabetologia. 2019;62[11]:2118-28) found an even higher proportion of GDM involving predominant insulin resistance and, similarly, a greater risk of adverse pregnancy outcomes in these women than in insulin-sensitive women with GDM, “again suggesting that there’s probably some benefit to looking deeper at physiology to understand individual risk,” she said.

Research published decades ago showed that insulin sensitivity decreases by over 50% during pregnancy, and “what we’ve come to recognize is there [can be] insulin secretion deficiency that’s not able to surmount or overcome the insulin resistance that develops during advanced gestation,” she said. “We need to think not at the population level but at the individual level.”

Dr. Feghali is leading the MATCh-GDM (Metabolic Analysis for Treatment Choice in GDM) study, which has been randomizing women to receive either usual, unmatched treatment or treatment matched to GDM mechanism — metformin for predominant insulin resistance, glyburide, or insulin for predominant insulin secretion defects, and one of the three for combined mechanisms. Data are not available yet.

There is still more to be learned about the pharmacologic effects of oral hypoglycemics, she noted, pointing to a 2020 study (Clin Pharmacol Ther. 2020;107[6]:1362-72) that randomized women to glyburide, metformin, or glyburide/metformin combination therapy and measured insulin sensitivity, beta-cell responsivity, and disposition index. (The latter describes the overall metabolic state and is a product of insulin sensitivity and total beta-cell responsivity.)

“Somewhat surprisingly, they found metformin performed better than glyburide,” shifting the overall disposition index closer to normal, Dr. Feghali said. “But not surprisingly, they found the combination worked best.”

Total beta-cell responsivity occurred in 56% of the glyburide group and 74% of the combination group. Improvements in insulin sensitivity occurred in 84% of the metformin group and 74% of the combination group. Surprisingly, there was “a decrease in first-phase insulin secretion” with glyburide, noted Dr. Feghali — a finding that means “the glyburide story has turned out to be a little more complicated.” With metformin, there was a positive change in insulin secretion as well as insulin sensitivity.

The authors’ conclusion, she noted, “is that there’s potential in thinking about metformin first, as the primary treatment, and then adding glyburide after that.”
 

Future Use Of Incretin Mimetics, and Intensive Targets in Overweight/Obesity

Dr. Feghali wonders whether incretin hormone mimetics — such as glucagonlike peptide–1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) — could play a future role in GDM treatment, helping to increase insulin secretion.

She is currently recruiting for a pilot study on the pharmacokinetics and pharmacodynamics in GDM of exenatide, a FDA-approved GLP-1 agonist that has been shown not to cross the placenta and that should, research suggests, lower the risk of maternal hypoglycemia and limit the risk of excessive fetal growth, “overcoming some of the concerns we have with glyburide,” Dr. Feghali said.

A recent study of the gut-generated incretin response during an oral glucose tolerance test in pregnant women with and without GDM showed that post-load GLP-1 and GIP were higher in women with GDM, and that the GLP-1 secretion was associated with insulin secretion only in those with GDM (J Clin Endocrinol Metab. 2022;107(6):e2425-30). “In those with normal OGTT, insulin secretion was independent of GLP-1,” she said. “This study suggests there’s a potential role for incretin mimetics in GDM.”

Also regarding the individualization of GDM treatment, patients who are overweight or obese in the prepregnancy setting and have gestational diabetes represent a different phenotype, she noted, with higher fasting and postprandial blood glucose compared to normal-weight counterparts despite higher doses of medication.

“After controlling for gestational weight gain and glycemic control, we see there’s an independent effect of prepregnancy obesity specifically for an increased risk of macrosomia, preterm birth, and hypertensive disorders of pregnancy,” said Dr. Feghali, referring to a 2015 retrospective study of GDM and obesity (Obstet Gynecol. 2015;126:316-25). “It suggests that we might think about redrawing the line, not on diagnosis and screening but on treatment.”

The randomized, controlled Intensive Glycemic Targets in Overweight and Obese Women with Gestational Diabetes Mellitus (iGDM) trial, is now recruiting at multiple centers, including at Dr. Feghali’s University of Pittsburgh, and will investigate the effect of intensive glycemic targets (fasting < 90 mg/dL, 1-hour postprandial < 120 mg/dL) versus standard glycemic targets (fasting < 95 mg/dL, 1-hour postprandial < 140 mg/dL), she said.

In another presentation on GDM, Monica Longo, MD, PhD, of the Inova Health System in Fairfax, Va., said researchers are also looking at whether nutritional supplements such as myo-inositol can reduce the risk of adverse pregnancy outcomes in GDM, and whether probiotics can improve insulin sensitivity in some patients.

Data on newer insulin analogs in pregnancy are lacking, she noted. “Preliminary data has shown no malformations in infants, but there is some increase in hypoglycemia-related admissions to the NICU,” she said. “It’s worth it [to research more].”

FAIRFAX, VIRGINIA — Pharmacologic treatment of gestational diabetes mellitus (GDM) remains challenged by overall poor trial quality, clinical practice guidelines that offer differing advice, and a limited ability to predict individual risk and treatment response, but researchers at the biennial meeting of the Diabetes in Pregnancy Study Group of North America expressed hope for more clarity in the near future and the ability to someday individualize treatment to account for what is increasingly viewed as a heterogeneous condition.

Until studies in 2015 and 2018 cast doubt on glyburide, “we used to have 80% [of our GDM patients] on glyburide, and 20% on insulin,” Maisa Feghali, MD, of the University of Pittsburgh, said during a discussion period. “Now we have 95% on insulin and 5% on oral hypoglycemics. I rely on insulin because I don’t have a better option, and I rely on research efforts [underway to provide better options]” in the future.

The American College of Obstetricians and Gynecologists recommends insulin as the preferred first-line pharmacologic therapy for GDM when pharmacologic therapy is needed, with metformin as an option when patients decline or cannot safely use insulin. Glyburide, ACOG said in its 2018 practice bulletin on GDM (Obstet Gynecol. 2018;131[2]:e49-64), should not be recommended as a first-line pharmacologic therapy.

The Society of Maternal-Fetal Medicine, on the other hand, has accepted metformin as a “reasonable and safe” first-line alternative to insulin — while recognizing that half of women will still require insulin to achieve glycemic control — and does not rule out consideration of glyburide. In its 2018 statement on the pharmacologic treatment of GDM, the society said that the evidence of benefit of one oral agent over another remains limited.  

“When you have dueling guidelines, it means the data are not that clear,” George Saade, MD, professor and chair of obstetrics and gynecology at the Eastern Virginia School of Medicine, Norfolk, said in a presentation on GDM. An upcoming $12 million multicenter study to be led by the Ohio State University College of Medicine — coined the DECIDE trial — should provide clarity, he said.

The trial, funded by the Patient-Centered Outcomes Research Institute, which funds comparative clinical effectiveness research designed to be broadly applicable to practice, will enroll and randomize over 1500 pregnant individuals with GDM to either oral metformin or insulin and will follow mothers and children until 2 years after delivery.

The study’s primary and secondary hypotheses, respectively, are that metformin is not inferior to insulin in reducing a composite adverse neonatal outcome (large for gestational age, neonatal hypoglycemia and/or hyperbilirubemia) and that metformin does not result in increased child body mass index at 2 years, compared with insulin. It will also look at patient-reported factors associated with metformin use compared to insulin use — factors that “are important ... to enable clinical implementation of study findings,” said Dr. Saade, who played a role in designing the study over the past several years.

The study will take a pragmatic, real-world approach by ensuring racial and ethnic, socioeconomic, urban and rural, and geographic diversity at both large academic and community-based sites across the United States.

The trial, to be led by Mark Landon, MD, and Kartik Venkatesh, MD, PhD, of Ohio State University, will be the first large trial in the United States to both directly compare the ability of oral hypoglycemics and insulin to prevent GDM-associated pregnancy complications, and to follow children for 2 years, Dr. Saade said. “Prior research was either outside the United States, not randomized, not adequately powered, or had no long-term child follow-up,” he added after the meeting.
 

The State Of Knowledge About Oral Hypoglycemics

The trial was envisioned several years ago as a three-arm comparative trial including the sulfonylurea glyburide, but data published in recent years has increasingly “not favored” glyburide, and many providers “have stopped using it,” Dr. Saade said during and after the meeting. At this point, “it would not be useful to include it” in a pragmatic trial, he said.

Glyburide became the number one agent after a seminal trial published in 2000 (N Engl J Med. 2000;343:1134-8) showed equivalent glycemic control in about 400 women with GDM who were randomized to receive insulin or glyburide. While the trial was not powered to evaluate other outcomes, there were no significant differences in neonatal complications.

In 2015, a large retrospective population-based study (JAMA Pediatr. 2015;169[5]:452-8) of more than 9,000 women with GDM showed higher risks of neonatal intensive care admission, neonatal hypoglycemia, and large-for-gestational age with glyburide compared with insulin. “It prompted a pause in thinking,” Dr. Saade recalled at the DPSG meeting. After that, several meta-analyses/systematic reviews compared the two treatments, showing varying and sometimes conflicting degrees of difference in neonatal outcomes.

In 2018, a French noninferiority randomized controlled trial (JAMA 2018;319[17]:1773-80) did not show that glyburide is not inferior to insulin in the prevention of perinatal outcomes (macrosomia, neonatal hypoglycemia, and hyperbilirubinemia). “If you add this trial to the systematic reviews, it would probably would shift more in favor of insulin,” Dr. Saade said, noting that the trial’s supplementary data included a higher rate of maternal hypoglycemia with glyburide. “I feel personally now, with all the data, that glyburide is inferior to insulin.”

A 2021 network meta-analysis (BMC Endocr Disord. 2021;21:199) that looked at glycemic control and neonatal outcomes in GDM treated with glyburide, metformin, or insulin, also offers valuable insight, Dr. Saade said. The meta-analysis used a Bayesian framework and presents results as a ranking estimated probability of a treatment being the best or worst — or in between — for different outcomes (glycemic control and neonatal outcomes), which “is one of the best ways to look at data these days,” he said.

“It tells us how likely [it is for one agent] to be better than others. Will it work most of the time? More than 60% of the time?” Dr. Saade explained. For example, the analysis “tell us that for large for gestational age, glyburide has a 94% chance of being the worst, metformin has an 80% change of being the best, and insulin a 76% chance of being in between.”

Overall, the 2021 analysis suggests that “glyburide is the most likely to be worst in most outcomes and that there is equipoise between metformin and insulin,” he said.

Meta-analyses of pharmacologic treatment of GDM have been challenged, he said, by inconsistent reporting in trials of GDM diagnostic criteria, severity of hyperglycemia, and small sample sizes (and wide confidence intervals). Criteria for supplemental insulin are also often “unclear” in trials, Dr. Saade said, as is involvement of social determinants of health and the “care package” enveloping pharmacologic interventions.

Dr. Saade, Dr. Landon, and other researchers have also lamented over the years that there is limited long-term follow-up of exposed offspring.
 

The Challenge of Heterogeneity

In another presentation on GDM, Maisa Feghali, MD, MS, emphasized that GDM is a heterogeneous condition, with clinical hyperglycemia not capturing individual variation in underlying physiologic processes. A 2016 study (Diabetes Care. 2016;39[6]:1052-5) assessing insulin sensitivity and secretion in 800-plus women at 24-30 weeks’ gestation found that about 50% of those with GDM had predominant insulin resistance, 30% had predominant insulin secretion deficit, and 20% were mixed.

Those with predominant insulin resistance had higher BMI, higher fasting glucose, larger infants, and greater risk of GDM-associated adverse outcomes, “suggesting that the risk is not universal or equivalent,” said Dr. Feghali, assistant professor in the department of obstetrics, gynecology and reproductive sciences at the University of Pittsburgh and the UPCM Magee-Women’s Hospital.

A 2019 multicenter European study (Diabetologia. 2019;62[11]:2118-28) found an even higher proportion of GDM involving predominant insulin resistance and, similarly, a greater risk of adverse pregnancy outcomes in these women than in insulin-sensitive women with GDM, “again suggesting that there’s probably some benefit to looking deeper at physiology to understand individual risk,” she said.

Research published decades ago showed that insulin sensitivity decreases by over 50% during pregnancy, and “what we’ve come to recognize is there [can be] insulin secretion deficiency that’s not able to surmount or overcome the insulin resistance that develops during advanced gestation,” she said. “We need to think not at the population level but at the individual level.”

Dr. Feghali is leading the MATCh-GDM (Metabolic Analysis for Treatment Choice in GDM) study, which has been randomizing women to receive either usual, unmatched treatment or treatment matched to GDM mechanism — metformin for predominant insulin resistance, glyburide, or insulin for predominant insulin secretion defects, and one of the three for combined mechanisms. Data are not available yet.

There is still more to be learned about the pharmacologic effects of oral hypoglycemics, she noted, pointing to a 2020 study (Clin Pharmacol Ther. 2020;107[6]:1362-72) that randomized women to glyburide, metformin, or glyburide/metformin combination therapy and measured insulin sensitivity, beta-cell responsivity, and disposition index. (The latter describes the overall metabolic state and is a product of insulin sensitivity and total beta-cell responsivity.)

“Somewhat surprisingly, they found metformin performed better than glyburide,” shifting the overall disposition index closer to normal, Dr. Feghali said. “But not surprisingly, they found the combination worked best.”

Total beta-cell responsivity occurred in 56% of the glyburide group and 74% of the combination group. Improvements in insulin sensitivity occurred in 84% of the metformin group and 74% of the combination group. Surprisingly, there was “a decrease in first-phase insulin secretion” with glyburide, noted Dr. Feghali — a finding that means “the glyburide story has turned out to be a little more complicated.” With metformin, there was a positive change in insulin secretion as well as insulin sensitivity.

The authors’ conclusion, she noted, “is that there’s potential in thinking about metformin first, as the primary treatment, and then adding glyburide after that.”
 

Future Use Of Incretin Mimetics, and Intensive Targets in Overweight/Obesity

Dr. Feghali wonders whether incretin hormone mimetics — such as glucagonlike peptide–1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) — could play a future role in GDM treatment, helping to increase insulin secretion.

She is currently recruiting for a pilot study on the pharmacokinetics and pharmacodynamics in GDM of exenatide, a FDA-approved GLP-1 agonist that has been shown not to cross the placenta and that should, research suggests, lower the risk of maternal hypoglycemia and limit the risk of excessive fetal growth, “overcoming some of the concerns we have with glyburide,” Dr. Feghali said.

A recent study of the gut-generated incretin response during an oral glucose tolerance test in pregnant women with and without GDM showed that post-load GLP-1 and GIP were higher in women with GDM, and that the GLP-1 secretion was associated with insulin secretion only in those with GDM (J Clin Endocrinol Metab. 2022;107(6):e2425-30). “In those with normal OGTT, insulin secretion was independent of GLP-1,” she said. “This study suggests there’s a potential role for incretin mimetics in GDM.”

Also regarding the individualization of GDM treatment, patients who are overweight or obese in the prepregnancy setting and have gestational diabetes represent a different phenotype, she noted, with higher fasting and postprandial blood glucose compared to normal-weight counterparts despite higher doses of medication.

“After controlling for gestational weight gain and glycemic control, we see there’s an independent effect of prepregnancy obesity specifically for an increased risk of macrosomia, preterm birth, and hypertensive disorders of pregnancy,” said Dr. Feghali, referring to a 2015 retrospective study of GDM and obesity (Obstet Gynecol. 2015;126:316-25). “It suggests that we might think about redrawing the line, not on diagnosis and screening but on treatment.”

The randomized, controlled Intensive Glycemic Targets in Overweight and Obese Women with Gestational Diabetes Mellitus (iGDM) trial, is now recruiting at multiple centers, including at Dr. Feghali’s University of Pittsburgh, and will investigate the effect of intensive glycemic targets (fasting < 90 mg/dL, 1-hour postprandial < 120 mg/dL) versus standard glycemic targets (fasting < 95 mg/dL, 1-hour postprandial < 140 mg/dL), she said.

In another presentation on GDM, Monica Longo, MD, PhD, of the Inova Health System in Fairfax, Va., said researchers are also looking at whether nutritional supplements such as myo-inositol can reduce the risk of adverse pregnancy outcomes in GDM, and whether probiotics can improve insulin sensitivity in some patients.

Data on newer insulin analogs in pregnancy are lacking, she noted. “Preliminary data has shown no malformations in infants, but there is some increase in hypoglycemia-related admissions to the NICU,” she said. “It’s worth it [to research more].”

FAIRFAX, VIRGINIA — Pharmacologic treatment of gestational diabetes mellitus (GDM) remains challenged by overall poor trial quality, clinical practice guidelines that offer differing advice, and a limited ability to predict individual risk and treatment response, but researchers at the biennial meeting of the Diabetes in Pregnancy Study Group of North America expressed hope for more clarity in the near future and the ability to someday individualize treatment to account for what is increasingly viewed as a heterogeneous condition.

Until studies in 2015 and 2018 cast doubt on glyburide, “we used to have 80% [of our GDM patients] on glyburide, and 20% on insulin,” Maisa Feghali, MD, of the University of Pittsburgh, said during a discussion period. “Now we have 95% on insulin and 5% on oral hypoglycemics. I rely on insulin because I don’t have a better option, and I rely on research efforts [underway to provide better options]” in the future.

The American College of Obstetricians and Gynecologists recommends insulin as the preferred first-line pharmacologic therapy for GDM when pharmacologic therapy is needed, with metformin as an option when patients decline or cannot safely use insulin. Glyburide, ACOG said in its 2018 practice bulletin on GDM (Obstet Gynecol. 2018;131[2]:e49-64), should not be recommended as a first-line pharmacologic therapy.

The Society of Maternal-Fetal Medicine, on the other hand, has accepted metformin as a “reasonable and safe” first-line alternative to insulin — while recognizing that half of women will still require insulin to achieve glycemic control — and does not rule out consideration of glyburide. In its 2018 statement on the pharmacologic treatment of GDM, the society said that the evidence of benefit of one oral agent over another remains limited.  

“When you have dueling guidelines, it means the data are not that clear,” George Saade, MD, professor and chair of obstetrics and gynecology at the Eastern Virginia School of Medicine, Norfolk, said in a presentation on GDM. An upcoming $12 million multicenter study to be led by the Ohio State University College of Medicine — coined the DECIDE trial — should provide clarity, he said.

The trial, funded by the Patient-Centered Outcomes Research Institute, which funds comparative clinical effectiveness research designed to be broadly applicable to practice, will enroll and randomize over 1500 pregnant individuals with GDM to either oral metformin or insulin and will follow mothers and children until 2 years after delivery.

The study’s primary and secondary hypotheses, respectively, are that metformin is not inferior to insulin in reducing a composite adverse neonatal outcome (large for gestational age, neonatal hypoglycemia and/or hyperbilirubemia) and that metformin does not result in increased child body mass index at 2 years, compared with insulin. It will also look at patient-reported factors associated with metformin use compared to insulin use — factors that “are important ... to enable clinical implementation of study findings,” said Dr. Saade, who played a role in designing the study over the past several years.

The study will take a pragmatic, real-world approach by ensuring racial and ethnic, socioeconomic, urban and rural, and geographic diversity at both large academic and community-based sites across the United States.

The trial, to be led by Mark Landon, MD, and Kartik Venkatesh, MD, PhD, of Ohio State University, will be the first large trial in the United States to both directly compare the ability of oral hypoglycemics and insulin to prevent GDM-associated pregnancy complications, and to follow children for 2 years, Dr. Saade said. “Prior research was either outside the United States, not randomized, not adequately powered, or had no long-term child follow-up,” he added after the meeting.
 

The State Of Knowledge About Oral Hypoglycemics

The trial was envisioned several years ago as a three-arm comparative trial including the sulfonylurea glyburide, but data published in recent years has increasingly “not favored” glyburide, and many providers “have stopped using it,” Dr. Saade said during and after the meeting. At this point, “it would not be useful to include it” in a pragmatic trial, he said.

Glyburide became the number one agent after a seminal trial published in 2000 (N Engl J Med. 2000;343:1134-8) showed equivalent glycemic control in about 400 women with GDM who were randomized to receive insulin or glyburide. While the trial was not powered to evaluate other outcomes, there were no significant differences in neonatal complications.

In 2015, a large retrospective population-based study (JAMA Pediatr. 2015;169[5]:452-8) of more than 9,000 women with GDM showed higher risks of neonatal intensive care admission, neonatal hypoglycemia, and large-for-gestational age with glyburide compared with insulin. “It prompted a pause in thinking,” Dr. Saade recalled at the DPSG meeting. After that, several meta-analyses/systematic reviews compared the two treatments, showing varying and sometimes conflicting degrees of difference in neonatal outcomes.

In 2018, a French noninferiority randomized controlled trial (JAMA 2018;319[17]:1773-80) did not show that glyburide is not inferior to insulin in the prevention of perinatal outcomes (macrosomia, neonatal hypoglycemia, and hyperbilirubinemia). “If you add this trial to the systematic reviews, it would probably would shift more in favor of insulin,” Dr. Saade said, noting that the trial’s supplementary data included a higher rate of maternal hypoglycemia with glyburide. “I feel personally now, with all the data, that glyburide is inferior to insulin.”

A 2021 network meta-analysis (BMC Endocr Disord. 2021;21:199) that looked at glycemic control and neonatal outcomes in GDM treated with glyburide, metformin, or insulin, also offers valuable insight, Dr. Saade said. The meta-analysis used a Bayesian framework and presents results as a ranking estimated probability of a treatment being the best or worst — or in between — for different outcomes (glycemic control and neonatal outcomes), which “is one of the best ways to look at data these days,” he said.

“It tells us how likely [it is for one agent] to be better than others. Will it work most of the time? More than 60% of the time?” Dr. Saade explained. For example, the analysis “tell us that for large for gestational age, glyburide has a 94% chance of being the worst, metformin has an 80% change of being the best, and insulin a 76% chance of being in between.”

Overall, the 2021 analysis suggests that “glyburide is the most likely to be worst in most outcomes and that there is equipoise between metformin and insulin,” he said.

Meta-analyses of pharmacologic treatment of GDM have been challenged, he said, by inconsistent reporting in trials of GDM diagnostic criteria, severity of hyperglycemia, and small sample sizes (and wide confidence intervals). Criteria for supplemental insulin are also often “unclear” in trials, Dr. Saade said, as is involvement of social determinants of health and the “care package” enveloping pharmacologic interventions.

Dr. Saade, Dr. Landon, and other researchers have also lamented over the years that there is limited long-term follow-up of exposed offspring.
 

The Challenge of Heterogeneity

In another presentation on GDM, Maisa Feghali, MD, MS, emphasized that GDM is a heterogeneous condition, with clinical hyperglycemia not capturing individual variation in underlying physiologic processes. A 2016 study (Diabetes Care. 2016;39[6]:1052-5) assessing insulin sensitivity and secretion in 800-plus women at 24-30 weeks’ gestation found that about 50% of those with GDM had predominant insulin resistance, 30% had predominant insulin secretion deficit, and 20% were mixed.

Those with predominant insulin resistance had higher BMI, higher fasting glucose, larger infants, and greater risk of GDM-associated adverse outcomes, “suggesting that the risk is not universal or equivalent,” said Dr. Feghali, assistant professor in the department of obstetrics, gynecology and reproductive sciences at the University of Pittsburgh and the UPCM Magee-Women’s Hospital.

A 2019 multicenter European study (Diabetologia. 2019;62[11]:2118-28) found an even higher proportion of GDM involving predominant insulin resistance and, similarly, a greater risk of adverse pregnancy outcomes in these women than in insulin-sensitive women with GDM, “again suggesting that there’s probably some benefit to looking deeper at physiology to understand individual risk,” she said.

Research published decades ago showed that insulin sensitivity decreases by over 50% during pregnancy, and “what we’ve come to recognize is there [can be] insulin secretion deficiency that’s not able to surmount or overcome the insulin resistance that develops during advanced gestation,” she said. “We need to think not at the population level but at the individual level.”

Dr. Feghali is leading the MATCh-GDM (Metabolic Analysis for Treatment Choice in GDM) study, which has been randomizing women to receive either usual, unmatched treatment or treatment matched to GDM mechanism — metformin for predominant insulin resistance, glyburide, or insulin for predominant insulin secretion defects, and one of the three for combined mechanisms. Data are not available yet.

There is still more to be learned about the pharmacologic effects of oral hypoglycemics, she noted, pointing to a 2020 study (Clin Pharmacol Ther. 2020;107[6]:1362-72) that randomized women to glyburide, metformin, or glyburide/metformin combination therapy and measured insulin sensitivity, beta-cell responsivity, and disposition index. (The latter describes the overall metabolic state and is a product of insulin sensitivity and total beta-cell responsivity.)

“Somewhat surprisingly, they found metformin performed better than glyburide,” shifting the overall disposition index closer to normal, Dr. Feghali said. “But not surprisingly, they found the combination worked best.”

Total beta-cell responsivity occurred in 56% of the glyburide group and 74% of the combination group. Improvements in insulin sensitivity occurred in 84% of the metformin group and 74% of the combination group. Surprisingly, there was “a decrease in first-phase insulin secretion” with glyburide, noted Dr. Feghali — a finding that means “the glyburide story has turned out to be a little more complicated.” With metformin, there was a positive change in insulin secretion as well as insulin sensitivity.

The authors’ conclusion, she noted, “is that there’s potential in thinking about metformin first, as the primary treatment, and then adding glyburide after that.”
 

Future Use Of Incretin Mimetics, and Intensive Targets in Overweight/Obesity

Dr. Feghali wonders whether incretin hormone mimetics — such as glucagonlike peptide–1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) — could play a future role in GDM treatment, helping to increase insulin secretion.

She is currently recruiting for a pilot study on the pharmacokinetics and pharmacodynamics in GDM of exenatide, a FDA-approved GLP-1 agonist that has been shown not to cross the placenta and that should, research suggests, lower the risk of maternal hypoglycemia and limit the risk of excessive fetal growth, “overcoming some of the concerns we have with glyburide,” Dr. Feghali said.

A recent study of the gut-generated incretin response during an oral glucose tolerance test in pregnant women with and without GDM showed that post-load GLP-1 and GIP were higher in women with GDM, and that the GLP-1 secretion was associated with insulin secretion only in those with GDM (J Clin Endocrinol Metab. 2022;107(6):e2425-30). “In those with normal OGTT, insulin secretion was independent of GLP-1,” she said. “This study suggests there’s a potential role for incretin mimetics in GDM.”

Also regarding the individualization of GDM treatment, patients who are overweight or obese in the prepregnancy setting and have gestational diabetes represent a different phenotype, she noted, with higher fasting and postprandial blood glucose compared to normal-weight counterparts despite higher doses of medication.

“After controlling for gestational weight gain and glycemic control, we see there’s an independent effect of prepregnancy obesity specifically for an increased risk of macrosomia, preterm birth, and hypertensive disorders of pregnancy,” said Dr. Feghali, referring to a 2015 retrospective study of GDM and obesity (Obstet Gynecol. 2015;126:316-25). “It suggests that we might think about redrawing the line, not on diagnosis and screening but on treatment.”

The randomized, controlled Intensive Glycemic Targets in Overweight and Obese Women with Gestational Diabetes Mellitus (iGDM) trial, is now recruiting at multiple centers, including at Dr. Feghali’s University of Pittsburgh, and will investigate the effect of intensive glycemic targets (fasting < 90 mg/dL, 1-hour postprandial < 120 mg/dL) versus standard glycemic targets (fasting < 95 mg/dL, 1-hour postprandial < 140 mg/dL), she said.

In another presentation on GDM, Monica Longo, MD, PhD, of the Inova Health System in Fairfax, Va., said researchers are also looking at whether nutritional supplements such as myo-inositol can reduce the risk of adverse pregnancy outcomes in GDM, and whether probiotics can improve insulin sensitivity in some patients.

Data on newer insulin analogs in pregnancy are lacking, she noted. “Preliminary data has shown no malformations in infants, but there is some increase in hypoglycemia-related admissions to the NICU,” she said. “It’s worth it [to research more].”

FAIRFAX, VIRGINIA — The lack of data on optimal timing of delivery for pregnancies complicated by diabetes remains a major challenge in obstetrics — one with considerable implications given the high and rising prevalence of pregestational and gestational diabetes, Katherine Laughon Grantz, MD, MS, of the National Institute of Child Health and Human Development, said at the biennial meeting of the Diabetes in Pregnancy Study Group of North America.

“While 39-40 weeks might be ideal for low-risk pregnancies, the optimal timing for pregnancies with complications [like diabetes] is unknown,” said Dr. Grantz, a senior investigator in the NICHD’s epidemiology branch.

The percentage of mothers with gestational diabetes mellitus (GDM) increased from 6% in 2016 to 8% in 2021, according to the most recent data from the National Vital Statistics System of the Centers for Disease Control and Prevention (MMWR Morb Mortal Wkly Rep. 2023;72:16). Meanwhile, the prevalence of prepregnancy obesity, which raises the risk of gestational and type 2 diabetes, was 29% in 2019; this represents an 11% increase from 2015 (NCHS Data Brief. 2020;392:1-8) and has occurred across all maternal ages, races, ethnic groups, and educational levels, she said.

“The reason clinicians deliver pregnancies with diabetes earlier is because there’s a decreased risk of macrosomia, shoulder dystocia, and stillbirth. And these risks need to be balanced with the increased risk of neonatal morbidity and mortality associated with earlier delivery,” said Dr. Grantz, who noted during her talk that delivery timing also appears to influence long-term neurodevelopmental outcomes. “Yet despite [diabetes in pregnancy] being so common, there is complete uncertainty about when to deliver.”
 

ACOG Recommendations, Randomized Trials (New And Old)

The American College of Obstetricians and Gynecologists, in a Committee Opinion on Medically Indicated Late-Preterm and Early-Term Deliveries, published in collaboration with the Society of Maternal-Fetal Medicine, offers recommendations based on the type of diabetes and the level of control. For instance, the suggested delivery timing for well-controlled GDM is full term (39 0/7 to 40 6/7 weeks of gestation), while the recommendation for poorly controlled diabetes is individualized late preterm/early term management (Obstet Gynecol. 2021;138:e35-9).

In defining and evaluating control, she noted, “the clinical focus is on glucose, but there are likely other important parameters that are not taken into account ... which [could be] important when considering the timing of delivery.” Potentially important factors include estimated fetal weight, fetal growth velocity, lipids, and amino acids, she said.

ACOG’s recommendations are based mainly on retrospective data, Dr. Grantz said. Only two randomized controlled trials have investigated the timing of delivery in the context of diabetes, and both focused on cesarean section and were “generally underpowered to study neonatal outcomes,” she said.

The first RCT, published in 1993, enrolled 200 women with uncomplicated insulin-requiring diabetes (187 with GDM and 13 with pregestational diabetes) at 38 weeks of gestation, and compared active induction of labor within 5 days to expectant management. There was no significant difference in the cesarean delivery rate (the primary outcome), but rates of macrosomia and large for gestational age were higher in the expectant management group (27% vs. 15%, P = .05, and 23% vs. 10%, P = .02, respectively). Shoulder dystocia occurred in three deliveries, each of which was expectantly managed (Am J Obstet Gynecol. 1993;169[3]:611-5). Notably, the study included “only women with excellent glucose control,” Dr. Grantz said.

The second RCT, published in 2017 by a group in Italy, enrolled 425 patients with GDM (diagnosed by the International Association of Diabetes and Pregnancy Study Groups criteria) between week 38 and week 39 of gestation and similarly randomized them to induction of labor or expectant management. No difference in cesarean delivery was found (BJOG. 2017;124[4]:669-77). Induction of labor was associated with a higher risk of hyperbilirubinemia, and there was a trend toward a decreased risk of macrosomia, but again, the study was underpowered to detect differences in most outcomes, she said. (The study also was stopped early because of an inability to recruit, she noted.)

Dr. Grantz is currently recruiting for a randomized trial aimed at determining the optimal time between 37 and 39 weeks to initiate delivery — the time when neonatal morbidity and perinatal mortality risk is the lowest – for uncontrolled GDM-complicated pregnancies. The trial is designed to recruit up to 3,450 pregnant women with uncontrolled GDM and randomize the timing of their delivery (NCT05515744).

Those who are eligible for the study but do not consent to participate in randomization for delivery will be asked about chart review only (an estimated additional 3,000). The SPAN TIME study will also assess newborn development and behavior outcomes, as well as anthropometric measures, as secondary outcomes. An exploratory analysis will look for clinical, nonclinical or biochemical factors that could be helpful in optimizing delivery timing.

What Retrospective Studies Reveal

Factors that may influence the timing of delivery include the duration of neonatal exposure to hyperglycemia/hyperinsulinemia (pregestational vs. gestational diabetes), the level of diabetes control, and comorbidities (e.g. maternal renal disease or chronic hypertension). However, research “investigating how these factors influence morbidity and the timing of delivery is limited,” said Dr. Grantz.

Overall, it has been difficult through retrospective studies, she said, to investigate neonatal morbidity in diabetic pregnancies and tease apart the relative effects of diabetes as a precursor for early delivery and prematurity itself. Among the studies suggesting an independent risk of diabetes is a retrospective study focusing on neonatal respiratory morbidity — “one of the most common adverse outcomes associated with diabetes.”

The study, an analysis of the Consortium on Safe Labor study (an electronic medical record study of more than 220,000 singleton pregnancies), stratified morbidity by the probability of delivering at term (≥ 37 weeks). GDM and pregestational diabetes complicated 5.1% and 1.5% of the pregnancies, respectively, and were found to be associated with increased risks of neonatal respiratory morbidity compared to women without diabetes — regardless of the probability of delivering at term.

However, these associations were stronger with a higher probability of delivering at term, which suggests that the neonatal respiratory morbidity associated with diabetes is not fully explained by a greater propensity for prematurity (Am J Perinatol. 2017;34[11]:1160-8).

In addition, the rates of all neonatal respiratory morbidities and mortality were higher for pregestational diabetes compared with gestational diabetes, said Dr. Grantz, a senior author of the study. (Morbidities included neonatal intensive care unit admission, transient tachypnea of newborn, apnea, respiratory distress syndrome, mechanical ventilation, and stillbirth.)

The pathophysiology of diabetes and neonatal respiratory morbidity is “not fully known,” she said. It is believed that fetal hyperinsulinemia may cause delayed pulmonary maturation and there is evidence from animal studies that insulin decreases the incorporation of glucose and fatty acids into phospholipid phosphatidylglycerol. Indirect effects stem from the physiologic immaturity of earlier delivery and a higher cesarean delivery rate in pregnancies complicated by diabetes, Dr. Grantz said.

Among other retrospective studies was a population-based study from Canada (2004-2014), published in 2020, of large numbers of women with all types of diabetes and a comparison group of over 2.5 million without diabetes. For maternal morbidity/mortality, there were no significant differences by gestational age between iatrogenic delivery and expectant management among any form of diabetes. But for neonatal morbidity and mortality, the study found differences.

In women with gestational diabetes, iatrogenic delivery was associated with increased risk of neonatal morbidity/mortality at 36 and 37 weeks’ gestation and with decreased risk at weeks 38-40. Increased risk with iatrogenic delivery was also found for women with type 1 and type 2 diabetes at weeks 36 and 37 (Acta Obstet Gynecol Scand. 2020;99[3]:341-9).

Another retrospective study using California vital statistics (1997-2006) examined rates of stillbirth and infant death in women with GDM by gestational age at delivery (Am J Obstet Gynecol. 2012;206[4]:309.e1-e7). The 190,000-plus women with GDM had elevated risk of stillbirth at each gestational age compared to those without GDM, but “the [excess] risk for GDM was lowest at 38 weeks and again at 40 weeks,” Dr. Grantz said. The investigators concluded, she said, “that the risk of expectant management exceeded that of delivery at 38 weeks and beyond.”

Dr. Grantz reported no disclosures.

FAIRFAX, VIRGINIA — The lack of data on optimal timing of delivery for pregnancies complicated by diabetes remains a major challenge in obstetrics — one with considerable implications given the high and rising prevalence of pregestational and gestational diabetes, Katherine Laughon Grantz, MD, MS, of the National Institute of Child Health and Human Development, said at the biennial meeting of the Diabetes in Pregnancy Study Group of North America.

“While 39-40 weeks might be ideal for low-risk pregnancies, the optimal timing for pregnancies with complications [like diabetes] is unknown,” said Dr. Grantz, a senior investigator in the NICHD’s epidemiology branch.

The percentage of mothers with gestational diabetes mellitus (GDM) increased from 6% in 2016 to 8% in 2021, according to the most recent data from the National Vital Statistics System of the Centers for Disease Control and Prevention (MMWR Morb Mortal Wkly Rep. 2023;72:16). Meanwhile, the prevalence of prepregnancy obesity, which raises the risk of gestational and type 2 diabetes, was 29% in 2019; this represents an 11% increase from 2015 (NCHS Data Brief. 2020;392:1-8) and has occurred across all maternal ages, races, ethnic groups, and educational levels, she said.

“The reason clinicians deliver pregnancies with diabetes earlier is because there’s a decreased risk of macrosomia, shoulder dystocia, and stillbirth. And these risks need to be balanced with the increased risk of neonatal morbidity and mortality associated with earlier delivery,” said Dr. Grantz, who noted during her talk that delivery timing also appears to influence long-term neurodevelopmental outcomes. “Yet despite [diabetes in pregnancy] being so common, there is complete uncertainty about when to deliver.”
 

ACOG Recommendations, Randomized Trials (New And Old)

The American College of Obstetricians and Gynecologists, in a Committee Opinion on Medically Indicated Late-Preterm and Early-Term Deliveries, published in collaboration with the Society of Maternal-Fetal Medicine, offers recommendations based on the type of diabetes and the level of control. For instance, the suggested delivery timing for well-controlled GDM is full term (39 0/7 to 40 6/7 weeks of gestation), while the recommendation for poorly controlled diabetes is individualized late preterm/early term management (Obstet Gynecol. 2021;138:e35-9).

In defining and evaluating control, she noted, “the clinical focus is on glucose, but there are likely other important parameters that are not taken into account ... which [could be] important when considering the timing of delivery.” Potentially important factors include estimated fetal weight, fetal growth velocity, lipids, and amino acids, she said.

ACOG’s recommendations are based mainly on retrospective data, Dr. Grantz said. Only two randomized controlled trials have investigated the timing of delivery in the context of diabetes, and both focused on cesarean section and were “generally underpowered to study neonatal outcomes,” she said.

The first RCT, published in 1993, enrolled 200 women with uncomplicated insulin-requiring diabetes (187 with GDM and 13 with pregestational diabetes) at 38 weeks of gestation, and compared active induction of labor within 5 days to expectant management. There was no significant difference in the cesarean delivery rate (the primary outcome), but rates of macrosomia and large for gestational age were higher in the expectant management group (27% vs. 15%, P = .05, and 23% vs. 10%, P = .02, respectively). Shoulder dystocia occurred in three deliveries, each of which was expectantly managed (Am J Obstet Gynecol. 1993;169[3]:611-5). Notably, the study included “only women with excellent glucose control,” Dr. Grantz said.

The second RCT, published in 2017 by a group in Italy, enrolled 425 patients with GDM (diagnosed by the International Association of Diabetes and Pregnancy Study Groups criteria) between week 38 and week 39 of gestation and similarly randomized them to induction of labor or expectant management. No difference in cesarean delivery was found (BJOG. 2017;124[4]:669-77). Induction of labor was associated with a higher risk of hyperbilirubinemia, and there was a trend toward a decreased risk of macrosomia, but again, the study was underpowered to detect differences in most outcomes, she said. (The study also was stopped early because of an inability to recruit, she noted.)

Dr. Grantz is currently recruiting for a randomized trial aimed at determining the optimal time between 37 and 39 weeks to initiate delivery — the time when neonatal morbidity and perinatal mortality risk is the lowest – for uncontrolled GDM-complicated pregnancies. The trial is designed to recruit up to 3,450 pregnant women with uncontrolled GDM and randomize the timing of their delivery (NCT05515744).

Those who are eligible for the study but do not consent to participate in randomization for delivery will be asked about chart review only (an estimated additional 3,000). The SPAN TIME study will also assess newborn development and behavior outcomes, as well as anthropometric measures, as secondary outcomes. An exploratory analysis will look for clinical, nonclinical or biochemical factors that could be helpful in optimizing delivery timing.

What Retrospective Studies Reveal

Factors that may influence the timing of delivery include the duration of neonatal exposure to hyperglycemia/hyperinsulinemia (pregestational vs. gestational diabetes), the level of diabetes control, and comorbidities (e.g. maternal renal disease or chronic hypertension). However, research “investigating how these factors influence morbidity and the timing of delivery is limited,” said Dr. Grantz.

Overall, it has been difficult through retrospective studies, she said, to investigate neonatal morbidity in diabetic pregnancies and tease apart the relative effects of diabetes as a precursor for early delivery and prematurity itself. Among the studies suggesting an independent risk of diabetes is a retrospective study focusing on neonatal respiratory morbidity — “one of the most common adverse outcomes associated with diabetes.”

The study, an analysis of the Consortium on Safe Labor study (an electronic medical record study of more than 220,000 singleton pregnancies), stratified morbidity by the probability of delivering at term (≥ 37 weeks). GDM and pregestational diabetes complicated 5.1% and 1.5% of the pregnancies, respectively, and were found to be associated with increased risks of neonatal respiratory morbidity compared to women without diabetes — regardless of the probability of delivering at term.

However, these associations were stronger with a higher probability of delivering at term, which suggests that the neonatal respiratory morbidity associated with diabetes is not fully explained by a greater propensity for prematurity (Am J Perinatol. 2017;34[11]:1160-8).

In addition, the rates of all neonatal respiratory morbidities and mortality were higher for pregestational diabetes compared with gestational diabetes, said Dr. Grantz, a senior author of the study. (Morbidities included neonatal intensive care unit admission, transient tachypnea of newborn, apnea, respiratory distress syndrome, mechanical ventilation, and stillbirth.)

The pathophysiology of diabetes and neonatal respiratory morbidity is “not fully known,” she said. It is believed that fetal hyperinsulinemia may cause delayed pulmonary maturation and there is evidence from animal studies that insulin decreases the incorporation of glucose and fatty acids into phospholipid phosphatidylglycerol. Indirect effects stem from the physiologic immaturity of earlier delivery and a higher cesarean delivery rate in pregnancies complicated by diabetes, Dr. Grantz said.

Among other retrospective studies was a population-based study from Canada (2004-2014), published in 2020, of large numbers of women with all types of diabetes and a comparison group of over 2.5 million without diabetes. For maternal morbidity/mortality, there were no significant differences by gestational age between iatrogenic delivery and expectant management among any form of diabetes. But for neonatal morbidity and mortality, the study found differences.

In women with gestational diabetes, iatrogenic delivery was associated with increased risk of neonatal morbidity/mortality at 36 and 37 weeks’ gestation and with decreased risk at weeks 38-40. Increased risk with iatrogenic delivery was also found for women with type 1 and type 2 diabetes at weeks 36 and 37 (Acta Obstet Gynecol Scand. 2020;99[3]:341-9).

Another retrospective study using California vital statistics (1997-2006) examined rates of stillbirth and infant death in women with GDM by gestational age at delivery (Am J Obstet Gynecol. 2012;206[4]:309.e1-e7). The 190,000-plus women with GDM had elevated risk of stillbirth at each gestational age compared to those without GDM, but “the [excess] risk for GDM was lowest at 38 weeks and again at 40 weeks,” Dr. Grantz said. The investigators concluded, she said, “that the risk of expectant management exceeded that of delivery at 38 weeks and beyond.”

Dr. Grantz reported no disclosures.

FAIRFAX, VIRGINIA — The lack of data on optimal timing of delivery for pregnancies complicated by diabetes remains a major challenge in obstetrics — one with considerable implications given the high and rising prevalence of pregestational and gestational diabetes, Katherine Laughon Grantz, MD, MS, of the National Institute of Child Health and Human Development, said at the biennial meeting of the Diabetes in Pregnancy Study Group of North America.

“While 39-40 weeks might be ideal for low-risk pregnancies, the optimal timing for pregnancies with complications [like diabetes] is unknown,” said Dr. Grantz, a senior investigator in the NICHD’s epidemiology branch.

The percentage of mothers with gestational diabetes mellitus (GDM) increased from 6% in 2016 to 8% in 2021, according to the most recent data from the National Vital Statistics System of the Centers for Disease Control and Prevention (MMWR Morb Mortal Wkly Rep. 2023;72:16). Meanwhile, the prevalence of prepregnancy obesity, which raises the risk of gestational and type 2 diabetes, was 29% in 2019; this represents an 11% increase from 2015 (NCHS Data Brief. 2020;392:1-8) and has occurred across all maternal ages, races, ethnic groups, and educational levels, she said.

“The reason clinicians deliver pregnancies with diabetes earlier is because there’s a decreased risk of macrosomia, shoulder dystocia, and stillbirth. And these risks need to be balanced with the increased risk of neonatal morbidity and mortality associated with earlier delivery,” said Dr. Grantz, who noted during her talk that delivery timing also appears to influence long-term neurodevelopmental outcomes. “Yet despite [diabetes in pregnancy] being so common, there is complete uncertainty about when to deliver.”
 

ACOG Recommendations, Randomized Trials (New And Old)

The American College of Obstetricians and Gynecologists, in a Committee Opinion on Medically Indicated Late-Preterm and Early-Term Deliveries, published in collaboration with the Society of Maternal-Fetal Medicine, offers recommendations based on the type of diabetes and the level of control. For instance, the suggested delivery timing for well-controlled GDM is full term (39 0/7 to 40 6/7 weeks of gestation), while the recommendation for poorly controlled diabetes is individualized late preterm/early term management (Obstet Gynecol. 2021;138:e35-9).

In defining and evaluating control, she noted, “the clinical focus is on glucose, but there are likely other important parameters that are not taken into account ... which [could be] important when considering the timing of delivery.” Potentially important factors include estimated fetal weight, fetal growth velocity, lipids, and amino acids, she said.

ACOG’s recommendations are based mainly on retrospective data, Dr. Grantz said. Only two randomized controlled trials have investigated the timing of delivery in the context of diabetes, and both focused on cesarean section and were “generally underpowered to study neonatal outcomes,” she said.

The first RCT, published in 1993, enrolled 200 women with uncomplicated insulin-requiring diabetes (187 with GDM and 13 with pregestational diabetes) at 38 weeks of gestation, and compared active induction of labor within 5 days to expectant management. There was no significant difference in the cesarean delivery rate (the primary outcome), but rates of macrosomia and large for gestational age were higher in the expectant management group (27% vs. 15%, P = .05, and 23% vs. 10%, P = .02, respectively). Shoulder dystocia occurred in three deliveries, each of which was expectantly managed (Am J Obstet Gynecol. 1993;169[3]:611-5). Notably, the study included “only women with excellent glucose control,” Dr. Grantz said.

The second RCT, published in 2017 by a group in Italy, enrolled 425 patients with GDM (diagnosed by the International Association of Diabetes and Pregnancy Study Groups criteria) between week 38 and week 39 of gestation and similarly randomized them to induction of labor or expectant management. No difference in cesarean delivery was found (BJOG. 2017;124[4]:669-77). Induction of labor was associated with a higher risk of hyperbilirubinemia, and there was a trend toward a decreased risk of macrosomia, but again, the study was underpowered to detect differences in most outcomes, she said. (The study also was stopped early because of an inability to recruit, she noted.)

Dr. Grantz is currently recruiting for a randomized trial aimed at determining the optimal time between 37 and 39 weeks to initiate delivery — the time when neonatal morbidity and perinatal mortality risk is the lowest – for uncontrolled GDM-complicated pregnancies. The trial is designed to recruit up to 3,450 pregnant women with uncontrolled GDM and randomize the timing of their delivery (NCT05515744).

Those who are eligible for the study but do not consent to participate in randomization for delivery will be asked about chart review only (an estimated additional 3,000). The SPAN TIME study will also assess newborn development and behavior outcomes, as well as anthropometric measures, as secondary outcomes. An exploratory analysis will look for clinical, nonclinical or biochemical factors that could be helpful in optimizing delivery timing.

What Retrospective Studies Reveal

Factors that may influence the timing of delivery include the duration of neonatal exposure to hyperglycemia/hyperinsulinemia (pregestational vs. gestational diabetes), the level of diabetes control, and comorbidities (e.g. maternal renal disease or chronic hypertension). However, research “investigating how these factors influence morbidity and the timing of delivery is limited,” said Dr. Grantz.

Overall, it has been difficult through retrospective studies, she said, to investigate neonatal morbidity in diabetic pregnancies and tease apart the relative effects of diabetes as a precursor for early delivery and prematurity itself. Among the studies suggesting an independent risk of diabetes is a retrospective study focusing on neonatal respiratory morbidity — “one of the most common adverse outcomes associated with diabetes.”

The study, an analysis of the Consortium on Safe Labor study (an electronic medical record study of more than 220,000 singleton pregnancies), stratified morbidity by the probability of delivering at term (≥ 37 weeks). GDM and pregestational diabetes complicated 5.1% and 1.5% of the pregnancies, respectively, and were found to be associated with increased risks of neonatal respiratory morbidity compared to women without diabetes — regardless of the probability of delivering at term.

However, these associations were stronger with a higher probability of delivering at term, which suggests that the neonatal respiratory morbidity associated with diabetes is not fully explained by a greater propensity for prematurity (Am J Perinatol. 2017;34[11]:1160-8).

In addition, the rates of all neonatal respiratory morbidities and mortality were higher for pregestational diabetes compared with gestational diabetes, said Dr. Grantz, a senior author of the study. (Morbidities included neonatal intensive care unit admission, transient tachypnea of newborn, apnea, respiratory distress syndrome, mechanical ventilation, and stillbirth.)

The pathophysiology of diabetes and neonatal respiratory morbidity is “not fully known,” she said. It is believed that fetal hyperinsulinemia may cause delayed pulmonary maturation and there is evidence from animal studies that insulin decreases the incorporation of glucose and fatty acids into phospholipid phosphatidylglycerol. Indirect effects stem from the physiologic immaturity of earlier delivery and a higher cesarean delivery rate in pregnancies complicated by diabetes, Dr. Grantz said.

Among other retrospective studies was a population-based study from Canada (2004-2014), published in 2020, of large numbers of women with all types of diabetes and a comparison group of over 2.5 million without diabetes. For maternal morbidity/mortality, there were no significant differences by gestational age between iatrogenic delivery and expectant management among any form of diabetes. But for neonatal morbidity and mortality, the study found differences.

In women with gestational diabetes, iatrogenic delivery was associated with increased risk of neonatal morbidity/mortality at 36 and 37 weeks’ gestation and with decreased risk at weeks 38-40. Increased risk with iatrogenic delivery was also found for women with type 1 and type 2 diabetes at weeks 36 and 37 (Acta Obstet Gynecol Scand. 2020;99[3]:341-9).

Another retrospective study using California vital statistics (1997-2006) examined rates of stillbirth and infant death in women with GDM by gestational age at delivery (Am J Obstet Gynecol. 2012;206[4]:309.e1-e7). The 190,000-plus women with GDM had elevated risk of stillbirth at each gestational age compared to those without GDM, but “the [excess] risk for GDM was lowest at 38 weeks and again at 40 weeks,” Dr. Grantz said. The investigators concluded, she said, “that the risk of expectant management exceeded that of delivery at 38 weeks and beyond.”

Dr. Grantz reported no disclosures.

TOPLINE:

Routine clinical examination detects only 2.2% of second breast cancers during 10-year follow-up in women undergoing posttreatment surveillance after ductal carcinoma in situ (DCIS).

METHODOLOGY:

• National Comprehensive Cancer Network guidelines recommend DCIS surveillance with a physical exam every 6-12 months for 5 years and then annually with a mammogram every 12 months. Research, however, suggested clinical breast exams only detect 15% of second breast cancers.
• A retrospective cohort study of 1550 female members of Kaiser Permanente Northern California diagnosed with unilateral DCIS between January 1, 2008, and January 1, 2011, who were followed until 2021.
• Patients who developed a second breast cancer within 10 years of follow-up were identified from the electronic health records. The detection methods were categorized into three groups: Patient-detected, physician-detected, and imaging-detected.

TAKEAWAY:

• During follow-up, 11.5% of women developed a second breast cancer with a median time to diagnosis of 57 months. Among patients with second breast cancers, 43.0% were ipsilateral, 54.8% were contralateral, and 2.2% presented with distant metastases.
• Overall, patients had a median of five mammograms between years 1 and 6 of surveillance and a median of seven clinic visits with most providers completing a clinical examination during the visit.
• Second breast cancers were detected through imaging in 74.3% of cases compared with 20.1% detected by patients and only 2.2% detected by physicians during physical exams. The remaining 3.4% were detected incidentally from plastic surgery procedures unrelated to oncologic surveillance.
• Mammogram detected 99.2% of cases (132 of 133 cases) identified by imaging.

IN PRACTICE:

“Our findings highlight the importance of mammogram screening and patient education regarding self-detection and can inform future NCCN recommendations for DCIS survivorship care,” the authors concluded, adding that “decreasing the need for in-person breast examinations could allow for other effective methods of survivorship monitoring.”

SOURCE:

This study, led by Bethany T. Waites of Kaiser Permanente San Francisco Medical Center, San Francisco, California, was published online on December 28 in the Journal of the National Comprehensive Cancer Network.

LIMITATIONS:

The retrospective design may have introduced selection bias or confounding. The study’s follow-up period until 2021, including the initial 18 months of the COVID-19 pandemic, may have affected surveillance patterns.

DISCLOSURES:

This study was supported by the Kaiser Permanente Northern California Graduate Medical Education program. The authors declared no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

Routine clinical examination detects only 2.2% of second breast cancers during 10-year follow-up in women undergoing posttreatment surveillance after ductal carcinoma in situ (DCIS).

METHODOLOGY:

• National Comprehensive Cancer Network guidelines recommend DCIS surveillance with a physical exam every 6-12 months for 5 years and then annually with a mammogram every 12 months. Research, however, suggested clinical breast exams only detect 15% of second breast cancers.
• A retrospective cohort study of 1550 female members of Kaiser Permanente Northern California diagnosed with unilateral DCIS between January 1, 2008, and January 1, 2011, who were followed until 2021.
• Patients who developed a second breast cancer within 10 years of follow-up were identified from the electronic health records. The detection methods were categorized into three groups: Patient-detected, physician-detected, and imaging-detected.

TAKEAWAY:

• During follow-up, 11.5% of women developed a second breast cancer with a median time to diagnosis of 57 months. Among patients with second breast cancers, 43.0% were ipsilateral, 54.8% were contralateral, and 2.2% presented with distant metastases.
• Overall, patients had a median of five mammograms between years 1 and 6 of surveillance and a median of seven clinic visits with most providers completing a clinical examination during the visit.
• Second breast cancers were detected through imaging in 74.3% of cases compared with 20.1% detected by patients and only 2.2% detected by physicians during physical exams. The remaining 3.4% were detected incidentally from plastic surgery procedures unrelated to oncologic surveillance.
• Mammogram detected 99.2% of cases (132 of 133 cases) identified by imaging.

IN PRACTICE:

“Our findings highlight the importance of mammogram screening and patient education regarding self-detection and can inform future NCCN recommendations for DCIS survivorship care,” the authors concluded, adding that “decreasing the need for in-person breast examinations could allow for other effective methods of survivorship monitoring.”

SOURCE:

This study, led by Bethany T. Waites of Kaiser Permanente San Francisco Medical Center, San Francisco, California, was published online on December 28 in the Journal of the National Comprehensive Cancer Network.

LIMITATIONS:

The retrospective design may have introduced selection bias or confounding. The study’s follow-up period until 2021, including the initial 18 months of the COVID-19 pandemic, may have affected surveillance patterns.

DISCLOSURES:

This study was supported by the Kaiser Permanente Northern California Graduate Medical Education program. The authors declared no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

Routine clinical examination detects only 2.2% of second breast cancers during 10-year follow-up in women undergoing posttreatment surveillance after ductal carcinoma in situ (DCIS).

METHODOLOGY:

• National Comprehensive Cancer Network guidelines recommend DCIS surveillance with a physical exam every 6-12 months for 5 years and then annually with a mammogram every 12 months. Research, however, suggested clinical breast exams only detect 15% of second breast cancers.
• A retrospective cohort study of 1550 female members of Kaiser Permanente Northern California diagnosed with unilateral DCIS between January 1, 2008, and January 1, 2011, who were followed until 2021.
• Patients who developed a second breast cancer within 10 years of follow-up were identified from the electronic health records. The detection methods were categorized into three groups: Patient-detected, physician-detected, and imaging-detected.

TAKEAWAY:

• During follow-up, 11.5% of women developed a second breast cancer with a median time to diagnosis of 57 months. Among patients with second breast cancers, 43.0% were ipsilateral, 54.8% were contralateral, and 2.2% presented with distant metastases.
• Overall, patients had a median of five mammograms between years 1 and 6 of surveillance and a median of seven clinic visits with most providers completing a clinical examination during the visit.
• Second breast cancers were detected through imaging in 74.3% of cases compared with 20.1% detected by patients and only 2.2% detected by physicians during physical exams. The remaining 3.4% were detected incidentally from plastic surgery procedures unrelated to oncologic surveillance.
• Mammogram detected 99.2% of cases (132 of 133 cases) identified by imaging.

IN PRACTICE:

“Our findings highlight the importance of mammogram screening and patient education regarding self-detection and can inform future NCCN recommendations for DCIS survivorship care,” the authors concluded, adding that “decreasing the need for in-person breast examinations could allow for other effective methods of survivorship monitoring.”

SOURCE:

This study, led by Bethany T. Waites of Kaiser Permanente San Francisco Medical Center, San Francisco, California, was published online on December 28 in the Journal of the National Comprehensive Cancer Network.

LIMITATIONS:

The retrospective design may have introduced selection bias or confounding. The study’s follow-up period until 2021, including the initial 18 months of the COVID-19 pandemic, may have affected surveillance patterns.

DISCLOSURES:

This study was supported by the Kaiser Permanente Northern California Graduate Medical Education program. The authors declared no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

Among women diagnosed with rosacea, the impact of pregnancy on the disease is unpredictable.

METHODOLOGY:

• Few data beyond case reports exist about the course of rosacea during pregnancy.
• Researchers conducted a telephone survey of 39 women with a diagnosis of rosacea in the electronic medical records prior to the onset of pregnancy who had been admitted to Oregon Health & Science University for labor and delivery from June 27, 2015, to June 27, 2020.
• Patient global assessment of clear (0), mild (1), moderate (2), or severe (3) rosacea was rated across five timepoints: 1-3 months preconception; first, second, and third trimesters; and 6 weeks postpartum.

TAKEAWAY:

• The mean age of the survey participants was 35.5 years, the mean gestational age at delivery was 39.4 weeks, and most had singleton pregnancies.
• All but one study participant (97.4%) reported symptoms of erythematotelangiectatic rosacea, while 26 (67%) reported symptoms of papulopustular rosacea.
• Nearly half of the participants (19, 48.7%) said their rosacea worsened during pregnancy, 13 (33.3%) reported no change in rosacea severity during pregnancy, and 7 (17.9%) reported that their rosacea improved during pregnancy.
• Before conceiving, the mean rosacea severity score among participants was mild (1.10; 95% CI, 0.92-1.29) and did not change significantly over time, a reflection of individual variations. In addition, 83.3% of participants did not use prescription rosacea treatments prior to pregnancy, and 89.6% did not use them during pregnancy.

IN PRACTICE:

“Rosacea, like acne, lacks a predictable group effect, and instead, each individual may have a different response to the physiologic changes of pregnancy,” the authors concluded.

SOURCE:

Genevieve Benedetti, MD, MPP, of the Department of Dermatology at Oregon Health & Science University, Portland, Oregon, led the research, published as a research letter in the International Journal of Women’s Dermatology.

LIMITATIONS:

The small sample size, single-center design, and overall prevalence of mild disease limit the ability to detect change.

DISCLOSURES:

The researchers reported having no disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

Among women diagnosed with rosacea, the impact of pregnancy on the disease is unpredictable.

METHODOLOGY:

• Few data beyond case reports exist about the course of rosacea during pregnancy.
• Researchers conducted a telephone survey of 39 women with a diagnosis of rosacea in the electronic medical records prior to the onset of pregnancy who had been admitted to Oregon Health & Science University for labor and delivery from June 27, 2015, to June 27, 2020.
• Patient global assessment of clear (0), mild (1), moderate (2), or severe (3) rosacea was rated across five timepoints: 1-3 months preconception; first, second, and third trimesters; and 6 weeks postpartum.

TAKEAWAY:

• The mean age of the survey participants was 35.5 years, the mean gestational age at delivery was 39.4 weeks, and most had singleton pregnancies.
• All but one study participant (97.4%) reported symptoms of erythematotelangiectatic rosacea, while 26 (67%) reported symptoms of papulopustular rosacea.
• Nearly half of the participants (19, 48.7%) said their rosacea worsened during pregnancy, 13 (33.3%) reported no change in rosacea severity during pregnancy, and 7 (17.9%) reported that their rosacea improved during pregnancy.
• Before conceiving, the mean rosacea severity score among participants was mild (1.10; 95% CI, 0.92-1.29) and did not change significantly over time, a reflection of individual variations. In addition, 83.3% of participants did not use prescription rosacea treatments prior to pregnancy, and 89.6% did not use them during pregnancy.

IN PRACTICE:

“Rosacea, like acne, lacks a predictable group effect, and instead, each individual may have a different response to the physiologic changes of pregnancy,” the authors concluded.

SOURCE:

Genevieve Benedetti, MD, MPP, of the Department of Dermatology at Oregon Health & Science University, Portland, Oregon, led the research, published as a research letter in the International Journal of Women’s Dermatology.

LIMITATIONS:

The small sample size, single-center design, and overall prevalence of mild disease limit the ability to detect change.

DISCLOSURES:

The researchers reported having no disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

Among women diagnosed with rosacea, the impact of pregnancy on the disease is unpredictable.

METHODOLOGY:

• Few data beyond case reports exist about the course of rosacea during pregnancy.
• Researchers conducted a telephone survey of 39 women with a diagnosis of rosacea in the electronic medical records prior to the onset of pregnancy who had been admitted to Oregon Health & Science University for labor and delivery from June 27, 2015, to June 27, 2020.
• Patient global assessment of clear (0), mild (1), moderate (2), or severe (3) rosacea was rated across five timepoints: 1-3 months preconception; first, second, and third trimesters; and 6 weeks postpartum.

TAKEAWAY:

• The mean age of the survey participants was 35.5 years, the mean gestational age at delivery was 39.4 weeks, and most had singleton pregnancies.
• All but one study participant (97.4%) reported symptoms of erythematotelangiectatic rosacea, while 26 (67%) reported symptoms of papulopustular rosacea.
• Nearly half of the participants (19, 48.7%) said their rosacea worsened during pregnancy, 13 (33.3%) reported no change in rosacea severity during pregnancy, and 7 (17.9%) reported that their rosacea improved during pregnancy.
• Before conceiving, the mean rosacea severity score among participants was mild (1.10; 95% CI, 0.92-1.29) and did not change significantly over time, a reflection of individual variations. In addition, 83.3% of participants did not use prescription rosacea treatments prior to pregnancy, and 89.6% did not use them during pregnancy.

IN PRACTICE:

“Rosacea, like acne, lacks a predictable group effect, and instead, each individual may have a different response to the physiologic changes of pregnancy,” the authors concluded.

SOURCE:

Genevieve Benedetti, MD, MPP, of the Department of Dermatology at Oregon Health & Science University, Portland, Oregon, led the research, published as a research letter in the International Journal of Women’s Dermatology.

LIMITATIONS:

The small sample size, single-center design, and overall prevalence of mild disease limit the ability to detect change.

DISCLOSURES:

The researchers reported having no disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

The frequency of follow-up after fertility-sparing surgery for cervical cancer can be tailored based on high-risk human papillomavirus (HPV) tests and cytology.

METHODOLOGY:

• Among patients with early-stage cervical cancer, the optimal follow-up strategy to detect recurrence after fertility-sparing surgery remains unclear. The authors wanted to find out if follow-up could be tailored to the patient’s risk for recurrence instead of using the current inefficient one-size-fits-all approach.
• The retrospective cohort study, which used data from the Netherlands Cancer Registry and the Dutch Nationwide Pathology Databank, included 1462 patients aged 18-40 years with early-stage cervical cancer who received fertility-sparing surgery (large loop excision of the transformation zone, conization, or trachelectomy) between 2000 and 2020.
• The primary endpoint was the cumulative incidence of recurrent cervical intraepithelial neoplasia grade 2 or worse (CIN2+), including recurrent cervical cancer.
• The authors stratified the likelihood of recurrence by cytology and high-risk HPV results at the first follow-up visit within 12 months of fertility-sparing surgery; they also compared the cumulative incidence of recurrence — the number of new cases divided by all at-risk individuals over a specific interval — at four timepoints in 2 years (6, 12, 18, and 24 months).

TAKEAWAY:

• Overall, the 10-year recurrence-free survival for CIN2+ was 89.3%. Patients with high-grade cytology at the first follow-up had worse 10-year recurrence-free survival for CIN2+ (43.1%) than those who had normal (92.1%) and low-grade cytology (84.6%). Similarly for HPV status, patients positive for high-risk HPV at the first follow-up had worse 10-year recurrence-free survival rates for CIN2+ (73.6%) than those negative for high-risk HPV (91.1%).
• Patients negative for both high-risk HPV and high-grade cytology 6-24 months after fertility-sparing surgery had a cumulative incidence of recurrence of 0.0%-0.7% within 6 months of follow-up compared with 0.0%-33.3% among patients negative for high-risk HPV but who had high-grade cytology.
• By contrast, patients positive for high-risk HPV but not high-grade cytology had a cumulative incidence of recurrence of 0.0%-15.4% within 6 months of any follow-up visit compared with 50.0%-100.0% among those with both high-risk HPV and high-grade cytology.
• Patients who remained free of high-risk HPV and high-grade cytology at their 6-month and 12-month follow-ups had no disease recurrence over the next 6 months.

IN PRACTICE:

“Patients who are negative for high-risk HPV with normal or low-grade cytology at 6-24 months after fertility-sparing surgery could be offered a prolonged follow-up interval of 6 months,” the authors concluded, adding that this “group comprises 80% of all patients receiving fertility-sparing surgery.”

“Reducing the number of follow-up visits, and subsequently the number of follow-up tests, in patients with low risk for recurrence on the basis of co-testing has the potential to substantially reduce healthcare costs,” the authors explained.

SOURCE:

The study, led by Teska N. Schuurman, MD, of the Netherlands Cancer Institute, Amsterdam, was published in the December 2023 issue of The Lancet Oncology.

LIMITATIONS:

The retrospective design of the study meant that analysis was limited to available records, so data on patients’ symptoms, physical examinations, or colposcopic findings were not available. Follow-up biopsies, considered the gold standard for diagnosing recurrence, are not routine in the Netherlands, so recurrence could have been underreported.

DISCLOSURES:

The authors declared no competing interests.
 

A version of this article appeared on Medscape.com.

TOPLINE:

The frequency of follow-up after fertility-sparing surgery for cervical cancer can be tailored based on high-risk human papillomavirus (HPV) tests and cytology.

METHODOLOGY:

• Among patients with early-stage cervical cancer, the optimal follow-up strategy to detect recurrence after fertility-sparing surgery remains unclear. The authors wanted to find out if follow-up could be tailored to the patient’s risk for recurrence instead of using the current inefficient one-size-fits-all approach.
• The retrospective cohort study, which used data from the Netherlands Cancer Registry and the Dutch Nationwide Pathology Databank, included 1462 patients aged 18-40 years with early-stage cervical cancer who received fertility-sparing surgery (large loop excision of the transformation zone, conization, or trachelectomy) between 2000 and 2020.
• The primary endpoint was the cumulative incidence of recurrent cervical intraepithelial neoplasia grade 2 or worse (CIN2+), including recurrent cervical cancer.
• The authors stratified the likelihood of recurrence by cytology and high-risk HPV results at the first follow-up visit within 12 months of fertility-sparing surgery; they also compared the cumulative incidence of recurrence — the number of new cases divided by all at-risk individuals over a specific interval — at four timepoints in 2 years (6, 12, 18, and 24 months).

TAKEAWAY:

• Overall, the 10-year recurrence-free survival for CIN2+ was 89.3%. Patients with high-grade cytology at the first follow-up had worse 10-year recurrence-free survival for CIN2+ (43.1%) than those who had normal (92.1%) and low-grade cytology (84.6%). Similarly for HPV status, patients positive for high-risk HPV at the first follow-up had worse 10-year recurrence-free survival rates for CIN2+ (73.6%) than those negative for high-risk HPV (91.1%).
• Patients negative for both high-risk HPV and high-grade cytology 6-24 months after fertility-sparing surgery had a cumulative incidence of recurrence of 0.0%-0.7% within 6 months of follow-up compared with 0.0%-33.3% among patients negative for high-risk HPV but who had high-grade cytology.
• By contrast, patients positive for high-risk HPV but not high-grade cytology had a cumulative incidence of recurrence of 0.0%-15.4% within 6 months of any follow-up visit compared with 50.0%-100.0% among those with both high-risk HPV and high-grade cytology.
• Patients who remained free of high-risk HPV and high-grade cytology at their 6-month and 12-month follow-ups had no disease recurrence over the next 6 months.

IN PRACTICE:

“Patients who are negative for high-risk HPV with normal or low-grade cytology at 6-24 months after fertility-sparing surgery could be offered a prolonged follow-up interval of 6 months,” the authors concluded, adding that this “group comprises 80% of all patients receiving fertility-sparing surgery.”

“Reducing the number of follow-up visits, and subsequently the number of follow-up tests, in patients with low risk for recurrence on the basis of co-testing has the potential to substantially reduce healthcare costs,” the authors explained.

SOURCE:

The study, led by Teska N. Schuurman, MD, of the Netherlands Cancer Institute, Amsterdam, was published in the December 2023 issue of The Lancet Oncology.

LIMITATIONS:

The retrospective design of the study meant that analysis was limited to available records, so data on patients’ symptoms, physical examinations, or colposcopic findings were not available. Follow-up biopsies, considered the gold standard for diagnosing recurrence, are not routine in the Netherlands, so recurrence could have been underreported.

DISCLOSURES:

The authors declared no competing interests.
 

A version of this article appeared on Medscape.com.

TOPLINE:

The frequency of follow-up after fertility-sparing surgery for cervical cancer can be tailored based on high-risk human papillomavirus (HPV) tests and cytology.

METHODOLOGY:

• Among patients with early-stage cervical cancer, the optimal follow-up strategy to detect recurrence after fertility-sparing surgery remains unclear. The authors wanted to find out if follow-up could be tailored to the patient’s risk for recurrence instead of using the current inefficient one-size-fits-all approach.
• The retrospective cohort study, which used data from the Netherlands Cancer Registry and the Dutch Nationwide Pathology Databank, included 1462 patients aged 18-40 years with early-stage cervical cancer who received fertility-sparing surgery (large loop excision of the transformation zone, conization, or trachelectomy) between 2000 and 2020.
• The primary endpoint was the cumulative incidence of recurrent cervical intraepithelial neoplasia grade 2 or worse (CIN2+), including recurrent cervical cancer.
• The authors stratified the likelihood of recurrence by cytology and high-risk HPV results at the first follow-up visit within 12 months of fertility-sparing surgery; they also compared the cumulative incidence of recurrence — the number of new cases divided by all at-risk individuals over a specific interval — at four timepoints in 2 years (6, 12, 18, and 24 months).

TAKEAWAY:

• Overall, the 10-year recurrence-free survival for CIN2+ was 89.3%. Patients with high-grade cytology at the first follow-up had worse 10-year recurrence-free survival for CIN2+ (43.1%) than those who had normal (92.1%) and low-grade cytology (84.6%). Similarly for HPV status, patients positive for high-risk HPV at the first follow-up had worse 10-year recurrence-free survival rates for CIN2+ (73.6%) than those negative for high-risk HPV (91.1%).
• Patients negative for both high-risk HPV and high-grade cytology 6-24 months after fertility-sparing surgery had a cumulative incidence of recurrence of 0.0%-0.7% within 6 months of follow-up compared with 0.0%-33.3% among patients negative for high-risk HPV but who had high-grade cytology.
• By contrast, patients positive for high-risk HPV but not high-grade cytology had a cumulative incidence of recurrence of 0.0%-15.4% within 6 months of any follow-up visit compared with 50.0%-100.0% among those with both high-risk HPV and high-grade cytology.
• Patients who remained free of high-risk HPV and high-grade cytology at their 6-month and 12-month follow-ups had no disease recurrence over the next 6 months.

IN PRACTICE:

“Patients who are negative for high-risk HPV with normal or low-grade cytology at 6-24 months after fertility-sparing surgery could be offered a prolonged follow-up interval of 6 months,” the authors concluded, adding that this “group comprises 80% of all patients receiving fertility-sparing surgery.”

“Reducing the number of follow-up visits, and subsequently the number of follow-up tests, in patients with low risk for recurrence on the basis of co-testing has the potential to substantially reduce healthcare costs,” the authors explained.

SOURCE:

The study, led by Teska N. Schuurman, MD, of the Netherlands Cancer Institute, Amsterdam, was published in the December 2023 issue of The Lancet Oncology.

LIMITATIONS:

The retrospective design of the study meant that analysis was limited to available records, so data on patients’ symptoms, physical examinations, or colposcopic findings were not available. Follow-up biopsies, considered the gold standard for diagnosing recurrence, are not routine in the Netherlands, so recurrence could have been underreported.

DISCLOSURES:

The authors declared no competing interests.
 

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

This is Dr JoAnn Manson, professor of medicine at Harvard Medical School and Brigham and Women’s Hospital. I’d like to talk with you about a recent report in JAMA Network Open on the subject of whether statin therapy may be able to offset some of the excess risk for venous thromboembolism (VTE) among women taking menopausal hormone therapy.

It’s an important issue because we know that menopausal hormone therapy, especially oral therapy, is linked to an excess risk for VTE, approximately doubling of risk in the randomized clinical trials. There is also emerging evidence from some randomized trials, such as the Jupiter trial, that step therapy may be linked to a reduction in risk. This may be related to anti-inflammatory or antithrombotic effects of statin therapy.

The authors made use of a very large administrative claims database, Optum Health, to look at more than 15 million annual members. They were able to identify 2000 women with a diagnostic code for VTE treatment. The women were between ages 50 and 64 years, and they were compared with 200,000 controls without VTE, matched in 10-to-1 fashion.

About 50% of the women were taking oral hormone therapy, and about 50% took non-oral transdermal or other non-oral formulations of hormone therapy. The odds ratio for VTE was 1.53 among the women who did not also have prescription records for statin therapy. They were able to look at prescribed prescriptions for both the hormone therapy and the statins. Among the women prescribed hormone therapy and also low- to intermediate-dose statins, the odds ratio was 1.29. So that was quite a mitigation of the elevated risk. Among the women taking high-intensity statins, the odds ratio was 1.06, and there was no significant elevation.

We do need more data and more research on this question. One approach would be a meta-analysis of all of the existing randomized trials of hormone therapy in recent years wherein there was increased uptake of statin therapy to look at this question not only for VTE but also for coronary heart disease, stroke, and other CVD outcomes to see whether statin therapy is associated with some attenuation of the excess risk. We also need a targeted randomized trial of statins vs placebo among women who have clear indications for hormone therapy but may be at some increased risk for VTE. That type of trial would be extremely helpful.

In the interim, there are ways to minimize risk for VTE among women who are clear candidates for menopausal hormone therapy, especially among women at increased risk for VTE. These include choosing a transdermal rather than an oral formulation of hormone therapy and using lower doses of hormone therapy. Also, women who are clear candidates for hormone therapy and also for statins, it’s obvious that statins could be co-prescribed. Even among women who are clear candidates for hormone therapy but only intermediate borderline candidates for statin therapy, the prescription of statins might be considered in that clinical scenario to try to mitigate that excess risk for VTE.

JoAnn E. Manson, MD, DrPH, has disclosed the following relevant financial relationships: Received study pill donation and infrastructure support from: Mars Symbioscience (for the COSMOS trial).

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

This is Dr JoAnn Manson, professor of medicine at Harvard Medical School and Brigham and Women’s Hospital. I’d like to talk with you about a recent report in JAMA Network Open on the subject of whether statin therapy may be able to offset some of the excess risk for venous thromboembolism (VTE) among women taking menopausal hormone therapy.

It’s an important issue because we know that menopausal hormone therapy, especially oral therapy, is linked to an excess risk for VTE, approximately doubling of risk in the randomized clinical trials. There is also emerging evidence from some randomized trials, such as the Jupiter trial, that step therapy may be linked to a reduction in risk. This may be related to anti-inflammatory or antithrombotic effects of statin therapy.

The authors made use of a very large administrative claims database, Optum Health, to look at more than 15 million annual members. They were able to identify 2000 women with a diagnostic code for VTE treatment. The women were between ages 50 and 64 years, and they were compared with 200,000 controls without VTE, matched in 10-to-1 fashion.

About 50% of the women were taking oral hormone therapy, and about 50% took non-oral transdermal or other non-oral formulations of hormone therapy. The odds ratio for VTE was 1.53 among the women who did not also have prescription records for statin therapy. They were able to look at prescribed prescriptions for both the hormone therapy and the statins. Among the women prescribed hormone therapy and also low- to intermediate-dose statins, the odds ratio was 1.29. So that was quite a mitigation of the elevated risk. Among the women taking high-intensity statins, the odds ratio was 1.06, and there was no significant elevation.

We do need more data and more research on this question. One approach would be a meta-analysis of all of the existing randomized trials of hormone therapy in recent years wherein there was increased uptake of statin therapy to look at this question not only for VTE but also for coronary heart disease, stroke, and other CVD outcomes to see whether statin therapy is associated with some attenuation of the excess risk. We also need a targeted randomized trial of statins vs placebo among women who have clear indications for hormone therapy but may be at some increased risk for VTE. That type of trial would be extremely helpful.

In the interim, there are ways to minimize risk for VTE among women who are clear candidates for menopausal hormone therapy, especially among women at increased risk for VTE. These include choosing a transdermal rather than an oral formulation of hormone therapy and using lower doses of hormone therapy. Also, women who are clear candidates for hormone therapy and also for statins, it’s obvious that statins could be co-prescribed. Even among women who are clear candidates for hormone therapy but only intermediate borderline candidates for statin therapy, the prescription of statins might be considered in that clinical scenario to try to mitigate that excess risk for VTE.

JoAnn E. Manson, MD, DrPH, has disclosed the following relevant financial relationships: Received study pill donation and infrastructure support from: Mars Symbioscience (for the COSMOS trial).

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

This is Dr JoAnn Manson, professor of medicine at Harvard Medical School and Brigham and Women’s Hospital. I’d like to talk with you about a recent report in JAMA Network Open on the subject of whether statin therapy may be able to offset some of the excess risk for venous thromboembolism (VTE) among women taking menopausal hormone therapy.

It’s an important issue because we know that menopausal hormone therapy, especially oral therapy, is linked to an excess risk for VTE, approximately doubling of risk in the randomized clinical trials. There is also emerging evidence from some randomized trials, such as the Jupiter trial, that step therapy may be linked to a reduction in risk. This may be related to anti-inflammatory or antithrombotic effects of statin therapy.

The authors made use of a very large administrative claims database, Optum Health, to look at more than 15 million annual members. They were able to identify 2000 women with a diagnostic code for VTE treatment. The women were between ages 50 and 64 years, and they were compared with 200,000 controls without VTE, matched in 10-to-1 fashion.

About 50% of the women were taking oral hormone therapy, and about 50% took non-oral transdermal or other non-oral formulations of hormone therapy. The odds ratio for VTE was 1.53 among the women who did not also have prescription records for statin therapy. They were able to look at prescribed prescriptions for both the hormone therapy and the statins. Among the women prescribed hormone therapy and also low- to intermediate-dose statins, the odds ratio was 1.29. So that was quite a mitigation of the elevated risk. Among the women taking high-intensity statins, the odds ratio was 1.06, and there was no significant elevation.

We do need more data and more research on this question. One approach would be a meta-analysis of all of the existing randomized trials of hormone therapy in recent years wherein there was increased uptake of statin therapy to look at this question not only for VTE but also for coronary heart disease, stroke, and other CVD outcomes to see whether statin therapy is associated with some attenuation of the excess risk. We also need a targeted randomized trial of statins vs placebo among women who have clear indications for hormone therapy but may be at some increased risk for VTE. That type of trial would be extremely helpful.

In the interim, there are ways to minimize risk for VTE among women who are clear candidates for menopausal hormone therapy, especially among women at increased risk for VTE. These include choosing a transdermal rather than an oral formulation of hormone therapy and using lower doses of hormone therapy. Also, women who are clear candidates for hormone therapy and also for statins, it’s obvious that statins could be co-prescribed. Even among women who are clear candidates for hormone therapy but only intermediate borderline candidates for statin therapy, the prescription of statins might be considered in that clinical scenario to try to mitigate that excess risk for VTE.

JoAnn E. Manson, MD, DrPH, has disclosed the following relevant financial relationships: Received study pill donation and infrastructure support from: Mars Symbioscience (for the COSMOS trial).

A version of this article appeared on Medscape.com.

TOPLINE:

Women with estrogen receptor (ER)–positive, human epidermal growth factor receptor 2 (HER2)–negative invasive lobular carcinoma who are treated with endocrine therapy do not derive any additional survival benefit from neoadjuvant or adjuvant chemotherapy.

METHODOLOGY:

• Studies evaluating the long-term effects of chemotherapy in patients with invasive lobular carcinoma are limited and often “show inconclusive results,” the authors explained.
• Female patients diagnosed with ER-positive, HER2-negative invasive lobular carcinoma who received endocrine therapy were identified from the breast cancer database at Erasmus Medical Center, Rotterdam, the Netherlands.
• Linked information on patient and tumor characteristics, vital status, and treatment were then obtained from the Netherlands Cancer Registry.
• Patients also had to have an indication for chemotherapy based on lymph node status, tumor size, histologic tumor grade, and hormone receptor status, in line with national guidelines.
• Among 716 patients with ER-positive, HER2-negative invasive lobular carcinoma, 520 who had an indication for chemotherapy were included. Of those, 379 received chemotherapy and 141 did not.

TAKEAWAY:

• Patients who received chemotherapy were younger at diagnosis than those who did not (51 vs 61 years), had an earlier average year of diagnosis (2010 vs 2015), and had longer follow-up (7.8 years vs 5.2 years).
• Chemotherapy recipients were more likely to have T3+ disease (33% vs 14%) and positive lymph node involvement (80% vs 49%), and less likely to undergo breast-conserving surgery (31% vs 43%).
• Researchers, however, found no difference between the chemotherapy and no-chemotherapy groups in terms of recurrence-free survival (hazard ratio [HR], 1.20; 95% CI, 0.63-2.31), breast cancer–specific survival (HR, 1.24; 95% CI, 0.60-2.58), and overall survival (HR, 0.97; 95% CI, 0.56-1.66) after adjustment for confounders.

IN PRACTICE:

The authors “observed no evidence for added value of chemotherapy” for ER-positive, HER2-negative invasive lobular carcinoma who received endocrine therapy. “In view of the adverse effects of chemotherapy, our study takes an important step in answering a valuable question from the patient’s perspective,” the researchers wrote.

SOURCE:

The study, conducted by Bernadette A.M. Heemskerk-Gerritsen, PhD, from Erasmus Medical Center Cancer Institute, Rotterdam, the Netherlands, was published in Cancer on November 20, 2023.

LIMITATIONS:

The retrospective design means that there is a risk for residual confounding from factors not recorded in the database. The researchers believe that some patients did not receive chemotherapy owing to having comorbidities or patient preference, which could have influenced the results. Moreover, the duration of endocrine therapy was not recorded.

DISCLOSURES:

No funding was declared. One author declares relationships with GlaxoSmithKline, Pfizer, Menarini Silicon Biosystems, and Novartis. No other relevant financial relationships were declared.

TOPLINE:

Women with estrogen receptor (ER)–positive, human epidermal growth factor receptor 2 (HER2)–negative invasive lobular carcinoma who are treated with endocrine therapy do not derive any additional survival benefit from neoadjuvant or adjuvant chemotherapy.

METHODOLOGY:

• Studies evaluating the long-term effects of chemotherapy in patients with invasive lobular carcinoma are limited and often “show inconclusive results,” the authors explained.
• Female patients diagnosed with ER-positive, HER2-negative invasive lobular carcinoma who received endocrine therapy were identified from the breast cancer database at Erasmus Medical Center, Rotterdam, the Netherlands.
• Linked information on patient and tumor characteristics, vital status, and treatment were then obtained from the Netherlands Cancer Registry.
• Patients also had to have an indication for chemotherapy based on lymph node status, tumor size, histologic tumor grade, and hormone receptor status, in line with national guidelines.
• Among 716 patients with ER-positive, HER2-negative invasive lobular carcinoma, 520 who had an indication for chemotherapy were included. Of those, 379 received chemotherapy and 141 did not.

TAKEAWAY:

• Patients who received chemotherapy were younger at diagnosis than those who did not (51 vs 61 years), had an earlier average year of diagnosis (2010 vs 2015), and had longer follow-up (7.8 years vs 5.2 years).
• Chemotherapy recipients were more likely to have T3+ disease (33% vs 14%) and positive lymph node involvement (80% vs 49%), and less likely to undergo breast-conserving surgery (31% vs 43%).
• Researchers, however, found no difference between the chemotherapy and no-chemotherapy groups in terms of recurrence-free survival (hazard ratio [HR], 1.20; 95% CI, 0.63-2.31), breast cancer–specific survival (HR, 1.24; 95% CI, 0.60-2.58), and overall survival (HR, 0.97; 95% CI, 0.56-1.66) after adjustment for confounders.

IN PRACTICE:

The authors “observed no evidence for added value of chemotherapy” for ER-positive, HER2-negative invasive lobular carcinoma who received endocrine therapy. “In view of the adverse effects of chemotherapy, our study takes an important step in answering a valuable question from the patient’s perspective,” the researchers wrote.

SOURCE:

The study, conducted by Bernadette A.M. Heemskerk-Gerritsen, PhD, from Erasmus Medical Center Cancer Institute, Rotterdam, the Netherlands, was published in Cancer on November 20, 2023.

LIMITATIONS:

The retrospective design means that there is a risk for residual confounding from factors not recorded in the database. The researchers believe that some patients did not receive chemotherapy owing to having comorbidities or patient preference, which could have influenced the results. Moreover, the duration of endocrine therapy was not recorded.

DISCLOSURES:

No funding was declared. One author declares relationships with GlaxoSmithKline, Pfizer, Menarini Silicon Biosystems, and Novartis. No other relevant financial relationships were declared.

TOPLINE:

Women with estrogen receptor (ER)–positive, human epidermal growth factor receptor 2 (HER2)–negative invasive lobular carcinoma who are treated with endocrine therapy do not derive any additional survival benefit from neoadjuvant or adjuvant chemotherapy.

METHODOLOGY:

• Studies evaluating the long-term effects of chemotherapy in patients with invasive lobular carcinoma are limited and often “show inconclusive results,” the authors explained.
• Female patients diagnosed with ER-positive, HER2-negative invasive lobular carcinoma who received endocrine therapy were identified from the breast cancer database at Erasmus Medical Center, Rotterdam, the Netherlands.
• Linked information on patient and tumor characteristics, vital status, and treatment were then obtained from the Netherlands Cancer Registry.
• Patients also had to have an indication for chemotherapy based on lymph node status, tumor size, histologic tumor grade, and hormone receptor status, in line with national guidelines.
• Among 716 patients with ER-positive, HER2-negative invasive lobular carcinoma, 520 who had an indication for chemotherapy were included. Of those, 379 received chemotherapy and 141 did not.

TAKEAWAY:

• Patients who received chemotherapy were younger at diagnosis than those who did not (51 vs 61 years), had an earlier average year of diagnosis (2010 vs 2015), and had longer follow-up (7.8 years vs 5.2 years).
• Chemotherapy recipients were more likely to have T3+ disease (33% vs 14%) and positive lymph node involvement (80% vs 49%), and less likely to undergo breast-conserving surgery (31% vs 43%).
• Researchers, however, found no difference between the chemotherapy and no-chemotherapy groups in terms of recurrence-free survival (hazard ratio [HR], 1.20; 95% CI, 0.63-2.31), breast cancer–specific survival (HR, 1.24; 95% CI, 0.60-2.58), and overall survival (HR, 0.97; 95% CI, 0.56-1.66) after adjustment for confounders.

IN PRACTICE:

The authors “observed no evidence for added value of chemotherapy” for ER-positive, HER2-negative invasive lobular carcinoma who received endocrine therapy. “In view of the adverse effects of chemotherapy, our study takes an important step in answering a valuable question from the patient’s perspective,” the researchers wrote.

SOURCE:

The study, conducted by Bernadette A.M. Heemskerk-Gerritsen, PhD, from Erasmus Medical Center Cancer Institute, Rotterdam, the Netherlands, was published in Cancer on November 20, 2023.

LIMITATIONS:

The retrospective design means that there is a risk for residual confounding from factors not recorded in the database. The researchers believe that some patients did not receive chemotherapy owing to having comorbidities or patient preference, which could have influenced the results. Moreover, the duration of endocrine therapy was not recorded.

DISCLOSURES:

No funding was declared. One author declares relationships with GlaxoSmithKline, Pfizer, Menarini Silicon Biosystems, and Novartis. No other relevant financial relationships were declared.

The past year has been a challenging time for many, both at the local level and globally, with divisive undercurrents across many communities. Many times, the end of the year is an opportunity for reflection. As I reflect on the state of perinatal psychiatry in the new year, I see several evolving issues that I’d like to share in this first column of 2024.

In 2023, the American College of Obstetricians and Gynecologists published new recommendations meant to enhance the well-being of pregnant and postpartum women and families. A main message from discussion papers borne out of these recommendations was that as a field, we should be doing more than identifying perinatal illness. We should be screening women at risk for postpartum psychiatric illness and see that those suffering from posttraumatic stress disorder (PTSD) have access to care and “wrap-around services” from clinicians with varying expertise.

Screening is a primary way we identify patients at risk for psychiatric illness and also those who are suffering at the time of a screen. One problem I see in the near future is our disparate collection and management of data. When we look closely across health care systems, it’s not clear how screening data are captured, let alone managed. What is being done in one hospital system may be very different from what is being done elsewhere. Some clinicians are adopting digital platforms to identify those with postpartum depression, while others are practicing as they always have, either through a paper screening process or with queries as part of a clinical encounter.

Given this amalgam of methods for collecting and storing information, there does not appear to be a systematic way clinicians and researchers are recording whether women are meeting criteria for significant depressive symptoms or frank postpartum psychiatric illness. It is clear a more cohesive method for collection and management is needed to optimize the likelihood that next steps can be taken to get patients the care they need.

However, screening is only one part of the story. Certainly, in our own center, one of our greatest interests, both clinically and on the research side, is what happens after screening. Through our center’s initiation of the Screening and Treatment Enhancement for Postpartum Depression (STEPS for PPD) project funded by the Marriott Foundation, we are evaluating the outcomes of women who are screened at 6 weeks postpartum with significant depressive symptoms, and who are then given an opportunity to engage with a perinatal social worker who can assist with direct psychotherapy, arranging for referrals, and navigating care for a new mother.

What we are learning as we enroll women through the initial stages of STEPS for PPD is that screening and identifying women who likely suffer from PPD simply is not enough. In fact, once identified with a depression screening tool, women who are suffering from postpartum depression can be very challenging to engage clinically. What I am learning decades after starting to work with perinatal patients is that even with a screening system and effective tools for treatment of PPD, optimizing engagement with these depressed women seems a critical and understudied step on the road to optimizing positive clinical outcomes.

A recent study published in the Journal of Women’s Health explored gaps in care for perinatal depression and found that patients without a history of psychiatric illness prior to pregnancy were less likely to be screened for depression and 80% less likely to receive care if they developed depression compared with women with a previous history of psychiatric illness (J Womens Health (Larchmt). 2023 Oct;32[10]:1111-9).

That history may help women navigate to care, while women for whom psychiatric illness is a new experience may be less likely to engage, be referred for care, and receive appropriate treatment. The study indicates that, as a field, we must strive to ensure universal screening for depression in perinatal populations.

While we have always been particularly interested in populations of patients at highest risk for PPD, helping women at risk for PPD in the general population without a history of psychiatric illness is a large public health issue and will be an even larger undertaking. As women’s mental health is gaining more appropriate focus, both at the local level and even in the recent White House Initiative on Women’s Health Research, the focus has been on screening and developing new treatments.

We are not lacking in pharmacologic agents nor nonpharmacologic options as treatments for women experiencing PPD. Newer alternative treatments are being explored, such as transcranial magnetic stimulation (TMS) and even psychedelics as a potential therapy for PPD. But perhaps what we’ve learned in 2023 and as we move into a new year, is that the problem of tackling PPD is not only about having the right tools, but is about helping women navigate to the care that they need.

The COVID-19 pandemic brought with it an explosion of telehealth options that have enhanced the odds women can find support during such a challenging time; as society has returned to some semblance of normal, nearly all support groups for postpartum women have remained online.

When we set up Virtual Rounds at the Center for Women’s Mental Health at the beginning of the pandemic, I was struck by the community of colleagues at various stages of their careers dedicated to mitigating the suffering associated with perinatal psychiatric illness. As I’ve often said, it takes a village to care for these patients. We need help from colleagues with varying expertise — from lactation consultants, psychiatrists, psychologists, obstetricians, nurse practitioners, support group leaders, and a host of others — who can help reach these women.

At the end of the day, helping depressed women find resources is a challenge that we have not met in this country. We should be excited that we have so many treatment options to offer patients — whether it be a new first-in-class medication, TMS, or digital apps to ensure patients are receiving effective treatment. But there should also be a focus on reaching women who still need treatment, particularly in underserved communities where resources are sparse or nonexistent. Identifying the path to reaching these women where they are and getting them well should be a top priority in 2024.
 

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

The past year has been a challenging time for many, both at the local level and globally, with divisive undercurrents across many communities. Many times, the end of the year is an opportunity for reflection. As I reflect on the state of perinatal psychiatry in the new year, I see several evolving issues that I’d like to share in this first column of 2024.

In 2023, the American College of Obstetricians and Gynecologists published new recommendations meant to enhance the well-being of pregnant and postpartum women and families. A main message from discussion papers borne out of these recommendations was that as a field, we should be doing more than identifying perinatal illness. We should be screening women at risk for postpartum psychiatric illness and see that those suffering from posttraumatic stress disorder (PTSD) have access to care and “wrap-around services” from clinicians with varying expertise.

Screening is a primary way we identify patients at risk for psychiatric illness and also those who are suffering at the time of a screen. One problem I see in the near future is our disparate collection and management of data. When we look closely across health care systems, it’s not clear how screening data are captured, let alone managed. What is being done in one hospital system may be very different from what is being done elsewhere. Some clinicians are adopting digital platforms to identify those with postpartum depression, while others are practicing as they always have, either through a paper screening process or with queries as part of a clinical encounter.

Given this amalgam of methods for collecting and storing information, there does not appear to be a systematic way clinicians and researchers are recording whether women are meeting criteria for significant depressive symptoms or frank postpartum psychiatric illness. It is clear a more cohesive method for collection and management is needed to optimize the likelihood that next steps can be taken to get patients the care they need.

However, screening is only one part of the story. Certainly, in our own center, one of our greatest interests, both clinically and on the research side, is what happens after screening. Through our center’s initiation of the Screening and Treatment Enhancement for Postpartum Depression (STEPS for PPD) project funded by the Marriott Foundation, we are evaluating the outcomes of women who are screened at 6 weeks postpartum with significant depressive symptoms, and who are then given an opportunity to engage with a perinatal social worker who can assist with direct psychotherapy, arranging for referrals, and navigating care for a new mother.

What we are learning as we enroll women through the initial stages of STEPS for PPD is that screening and identifying women who likely suffer from PPD simply is not enough. In fact, once identified with a depression screening tool, women who are suffering from postpartum depression can be very challenging to engage clinically. What I am learning decades after starting to work with perinatal patients is that even with a screening system and effective tools for treatment of PPD, optimizing engagement with these depressed women seems a critical and understudied step on the road to optimizing positive clinical outcomes.

A recent study published in the Journal of Women’s Health explored gaps in care for perinatal depression and found that patients without a history of psychiatric illness prior to pregnancy were less likely to be screened for depression and 80% less likely to receive care if they developed depression compared with women with a previous history of psychiatric illness (J Womens Health (Larchmt). 2023 Oct;32[10]:1111-9).

That history may help women navigate to care, while women for whom psychiatric illness is a new experience may be less likely to engage, be referred for care, and receive appropriate treatment. The study indicates that, as a field, we must strive to ensure universal screening for depression in perinatal populations.

While we have always been particularly interested in populations of patients at highest risk for PPD, helping women at risk for PPD in the general population without a history of psychiatric illness is a large public health issue and will be an even larger undertaking. As women’s mental health is gaining more appropriate focus, both at the local level and even in the recent White House Initiative on Women’s Health Research, the focus has been on screening and developing new treatments.

We are not lacking in pharmacologic agents nor nonpharmacologic options as treatments for women experiencing PPD. Newer alternative treatments are being explored, such as transcranial magnetic stimulation (TMS) and even psychedelics as a potential therapy for PPD. But perhaps what we’ve learned in 2023 and as we move into a new year, is that the problem of tackling PPD is not only about having the right tools, but is about helping women navigate to the care that they need.

The COVID-19 pandemic brought with it an explosion of telehealth options that have enhanced the odds women can find support during such a challenging time; as society has returned to some semblance of normal, nearly all support groups for postpartum women have remained online.

When we set up Virtual Rounds at the Center for Women’s Mental Health at the beginning of the pandemic, I was struck by the community of colleagues at various stages of their careers dedicated to mitigating the suffering associated with perinatal psychiatric illness. As I’ve often said, it takes a village to care for these patients. We need help from colleagues with varying expertise — from lactation consultants, psychiatrists, psychologists, obstetricians, nurse practitioners, support group leaders, and a host of others — who can help reach these women.

At the end of the day, helping depressed women find resources is a challenge that we have not met in this country. We should be excited that we have so many treatment options to offer patients — whether it be a new first-in-class medication, TMS, or digital apps to ensure patients are receiving effective treatment. But there should also be a focus on reaching women who still need treatment, particularly in underserved communities where resources are sparse or nonexistent. Identifying the path to reaching these women where they are and getting them well should be a top priority in 2024.
 

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

The past year has been a challenging time for many, both at the local level and globally, with divisive undercurrents across many communities. Many times, the end of the year is an opportunity for reflection. As I reflect on the state of perinatal psychiatry in the new year, I see several evolving issues that I’d like to share in this first column of 2024.

In 2023, the American College of Obstetricians and Gynecologists published new recommendations meant to enhance the well-being of pregnant and postpartum women and families. A main message from discussion papers borne out of these recommendations was that as a field, we should be doing more than identifying perinatal illness. We should be screening women at risk for postpartum psychiatric illness and see that those suffering from posttraumatic stress disorder (PTSD) have access to care and “wrap-around services” from clinicians with varying expertise.

Screening is a primary way we identify patients at risk for psychiatric illness and also those who are suffering at the time of a screen. One problem I see in the near future is our disparate collection and management of data. When we look closely across health care systems, it’s not clear how screening data are captured, let alone managed. What is being done in one hospital system may be very different from what is being done elsewhere. Some clinicians are adopting digital platforms to identify those with postpartum depression, while others are practicing as they always have, either through a paper screening process or with queries as part of a clinical encounter.

Given this amalgam of methods for collecting and storing information, there does not appear to be a systematic way clinicians and researchers are recording whether women are meeting criteria for significant depressive symptoms or frank postpartum psychiatric illness. It is clear a more cohesive method for collection and management is needed to optimize the likelihood that next steps can be taken to get patients the care they need.

However, screening is only one part of the story. Certainly, in our own center, one of our greatest interests, both clinically and on the research side, is what happens after screening. Through our center’s initiation of the Screening and Treatment Enhancement for Postpartum Depression (STEPS for PPD) project funded by the Marriott Foundation, we are evaluating the outcomes of women who are screened at 6 weeks postpartum with significant depressive symptoms, and who are then given an opportunity to engage with a perinatal social worker who can assist with direct psychotherapy, arranging for referrals, and navigating care for a new mother.

What we are learning as we enroll women through the initial stages of STEPS for PPD is that screening and identifying women who likely suffer from PPD simply is not enough. In fact, once identified with a depression screening tool, women who are suffering from postpartum depression can be very challenging to engage clinically. What I am learning decades after starting to work with perinatal patients is that even with a screening system and effective tools for treatment of PPD, optimizing engagement with these depressed women seems a critical and understudied step on the road to optimizing positive clinical outcomes.

A recent study published in the Journal of Women’s Health explored gaps in care for perinatal depression and found that patients without a history of psychiatric illness prior to pregnancy were less likely to be screened for depression and 80% less likely to receive care if they developed depression compared with women with a previous history of psychiatric illness (J Womens Health (Larchmt). 2023 Oct;32[10]:1111-9).

That history may help women navigate to care, while women for whom psychiatric illness is a new experience may be less likely to engage, be referred for care, and receive appropriate treatment. The study indicates that, as a field, we must strive to ensure universal screening for depression in perinatal populations.

While we have always been particularly interested in populations of patients at highest risk for PPD, helping women at risk for PPD in the general population without a history of psychiatric illness is a large public health issue and will be an even larger undertaking. As women’s mental health is gaining more appropriate focus, both at the local level and even in the recent White House Initiative on Women’s Health Research, the focus has been on screening and developing new treatments.

We are not lacking in pharmacologic agents nor nonpharmacologic options as treatments for women experiencing PPD. Newer alternative treatments are being explored, such as transcranial magnetic stimulation (TMS) and even psychedelics as a potential therapy for PPD. But perhaps what we’ve learned in 2023 and as we move into a new year, is that the problem of tackling PPD is not only about having the right tools, but is about helping women navigate to the care that they need.

The COVID-19 pandemic brought with it an explosion of telehealth options that have enhanced the odds women can find support during such a challenging time; as society has returned to some semblance of normal, nearly all support groups for postpartum women have remained online.

When we set up Virtual Rounds at the Center for Women’s Mental Health at the beginning of the pandemic, I was struck by the community of colleagues at various stages of their careers dedicated to mitigating the suffering associated with perinatal psychiatric illness. As I’ve often said, it takes a village to care for these patients. We need help from colleagues with varying expertise — from lactation consultants, psychiatrists, psychologists, obstetricians, nurse practitioners, support group leaders, and a host of others — who can help reach these women.

At the end of the day, helping depressed women find resources is a challenge that we have not met in this country. We should be excited that we have so many treatment options to offer patients — whether it be a new first-in-class medication, TMS, or digital apps to ensure patients are receiving effective treatment. But there should also be a focus on reaching women who still need treatment, particularly in underserved communities where resources are sparse or nonexistent. Identifying the path to reaching these women where they are and getting them well should be a top priority in 2024.
 

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

How can we improve the detection, assessment, and treatment of female sexual dysfunction?

Charlotte Methorst, MD, a urologist from Paris, and Carol Burté, MD, a sexologist and andrologist from Nice, dealt with these themes during a session at the French Urology Association’s 2023 conference, emphasizing the need for doctors to be involved in female sexual health.

“There’s currently a real disconnect; doctors talk very little about sexual health, yet it’s a topic that patients would really like to talk about. And this is even truer for women,” said Dr. Methorst.

“We need to spot sexual dysfunction because the topic is rarely broached spontaneously by female patients (19%) and even less so by healthcare workers (9%). Nowadays, it’s a very common problem (40%). Sexual dysfunction affects quality of life and a couple’s relationship. It also can reveal other conditions,” added Dr. Burté.
 

Spot and Assess

In terms of detecting the condition, the reference tool is the self-assessed Female Sexual Function Index, which comprises 19 questions covering six areas of sexual dysfunction: Desire, subjective arousal, lubrication, orgasm, satisfaction, and pain or discomfort.

But it is also possible to use the Sexual Complaints Screener for Women that evaluates sexual health over the past 6 months, explains Dr. Burté. For example, the patient is asked if she has had a lack of or low interest in sex or sexual desire in the past 6 months and if this has been a problem. She is also asked if she has experienced any pain during or after sexual activity.

To understand the root cause of sexual dysfunction, clinicians need to investigate the patient’s sexual health and perform a medical assessment. It’s also essential to ask the patient about her previous sexual, medical, and psychological history and to evaluate the couple and contributory factors, such as stress, fatigue, etc. This approach is known as the biopsychosocial model.

Once the contributory factors have been determined, relevant information can be given to the patient about her specific sexual problem, and the most suitable therapeutic approaches can be discussed with her.
 

Which Treatment Pathway?

Some problems may be improved with simple advice and lifestyle changes, but sex therapy and medication are options in other cases, explained the two doctors. “Since the causes of sexual dysfunction in women are mostly multifactorial, an integrative approach is needed,” said Dr. Burté.

The two main types of therapy that might be proposed for sexual dysfunction are sex therapies with cognitive behavioral therapy (CBT) and certain medicines being used as first-line treatment.

Using CBT in sexology requires patients and therapists to look past prejudices, preconceived ideas, and dysfunctional patterns and learn new behavioral, cognitive, and attentional strategies in terms of sexual health, regardless of whether an individual or couple is being treated.
 

Which Medicines?

Vasoactive drugs such as phosphodiesterase 5 inhibitors and prostaglandin have produced disappointing results. Drugs that act on the central nervous system to stimulate sexual desire, such as bremelanotide and flibanserin, don’t have marketing authorization in France due to their “insufficient” risk-benefit ratio.

However, topical hormone treatments (such as estrogen and dehydroepiandrosterone) are often used, particularly for cases of recurrent cystitis, in postmenopausal women and to treat urinary incontinence. “These topical treatments are very effective and can really change the life of a woman who no longer has a sex life because she is in discomfort and simply has dryness of the vulva and vagina,” said Dr. Burté, who recommends prescribing creams, which are better tolerated than pessaries.

General hormone treatments, hormone replacement therapy (HRT), and tibolone are prescribed to postmenopausal women.

Another option not yet authorized in France is testosterone because sexual desire depends on this hormone. An international consensus (2019, 10 learned societies) and recommendations made by the International Society for the Study of Women’s Sexual Health advise treatment with testosterone in the postmenopausal period, with or without HRT. The dose prescribed is a 10th of the male dose administered subcutaneously (300 µ/d) once a woman›s blood testosterone level has been determined to make sure there is an actual deficiency and to restore her testosterone to near premenopausal levels.

Both doctors indicated that having the chance to work with other doctors as part of a network is essential, especially with a sexual health specialist, if necessary.

Dr. Burté reported no conflicts of interest regarding the content of this article. Dr. Methorst reported relationships with several pharmaceutical laboratories.

This article was translated from the Medscape French edition.

How can we improve the detection, assessment, and treatment of female sexual dysfunction?

Charlotte Methorst, MD, a urologist from Paris, and Carol Burté, MD, a sexologist and andrologist from Nice, dealt with these themes during a session at the French Urology Association’s 2023 conference, emphasizing the need for doctors to be involved in female sexual health.

“There’s currently a real disconnect; doctors talk very little about sexual health, yet it’s a topic that patients would really like to talk about. And this is even truer for women,” said Dr. Methorst.

“We need to spot sexual dysfunction because the topic is rarely broached spontaneously by female patients (19%) and even less so by healthcare workers (9%). Nowadays, it’s a very common problem (40%). Sexual dysfunction affects quality of life and a couple’s relationship. It also can reveal other conditions,” added Dr. Burté.
 

Spot and Assess

In terms of detecting the condition, the reference tool is the self-assessed Female Sexual Function Index, which comprises 19 questions covering six areas of sexual dysfunction: Desire, subjective arousal, lubrication, orgasm, satisfaction, and pain or discomfort.

But it is also possible to use the Sexual Complaints Screener for Women that evaluates sexual health over the past 6 months, explains Dr. Burté. For example, the patient is asked if she has had a lack of or low interest in sex or sexual desire in the past 6 months and if this has been a problem. She is also asked if she has experienced any pain during or after sexual activity.

To understand the root cause of sexual dysfunction, clinicians need to investigate the patient’s sexual health and perform a medical assessment. It’s also essential to ask the patient about her previous sexual, medical, and psychological history and to evaluate the couple and contributory factors, such as stress, fatigue, etc. This approach is known as the biopsychosocial model.

Once the contributory factors have been determined, relevant information can be given to the patient about her specific sexual problem, and the most suitable therapeutic approaches can be discussed with her.
 

Which Treatment Pathway?

Some problems may be improved with simple advice and lifestyle changes, but sex therapy and medication are options in other cases, explained the two doctors. “Since the causes of sexual dysfunction in women are mostly multifactorial, an integrative approach is needed,” said Dr. Burté.

The two main types of therapy that might be proposed for sexual dysfunction are sex therapies with cognitive behavioral therapy (CBT) and certain medicines being used as first-line treatment.

Using CBT in sexology requires patients and therapists to look past prejudices, preconceived ideas, and dysfunctional patterns and learn new behavioral, cognitive, and attentional strategies in terms of sexual health, regardless of whether an individual or couple is being treated.
 

Which Medicines?

Vasoactive drugs such as phosphodiesterase 5 inhibitors and prostaglandin have produced disappointing results. Drugs that act on the central nervous system to stimulate sexual desire, such as bremelanotide and flibanserin, don’t have marketing authorization in France due to their “insufficient” risk-benefit ratio.

However, topical hormone treatments (such as estrogen and dehydroepiandrosterone) are often used, particularly for cases of recurrent cystitis, in postmenopausal women and to treat urinary incontinence. “These topical treatments are very effective and can really change the life of a woman who no longer has a sex life because she is in discomfort and simply has dryness of the vulva and vagina,” said Dr. Burté, who recommends prescribing creams, which are better tolerated than pessaries.

General hormone treatments, hormone replacement therapy (HRT), and tibolone are prescribed to postmenopausal women.

Another option not yet authorized in France is testosterone because sexual desire depends on this hormone. An international consensus (2019, 10 learned societies) and recommendations made by the International Society for the Study of Women’s Sexual Health advise treatment with testosterone in the postmenopausal period, with or without HRT. The dose prescribed is a 10th of the male dose administered subcutaneously (300 µ/d) once a woman›s blood testosterone level has been determined to make sure there is an actual deficiency and to restore her testosterone to near premenopausal levels.

Both doctors indicated that having the chance to work with other doctors as part of a network is essential, especially with a sexual health specialist, if necessary.

Dr. Burté reported no conflicts of interest regarding the content of this article. Dr. Methorst reported relationships with several pharmaceutical laboratories.

This article was translated from the Medscape French edition.

How can we improve the detection, assessment, and treatment of female sexual dysfunction?

Charlotte Methorst, MD, a urologist from Paris, and Carol Burté, MD, a sexologist and andrologist from Nice, dealt with these themes during a session at the French Urology Association’s 2023 conference, emphasizing the need for doctors to be involved in female sexual health.

“There’s currently a real disconnect; doctors talk very little about sexual health, yet it’s a topic that patients would really like to talk about. And this is even truer for women,” said Dr. Methorst.

“We need to spot sexual dysfunction because the topic is rarely broached spontaneously by female patients (19%) and even less so by healthcare workers (9%). Nowadays, it’s a very common problem (40%). Sexual dysfunction affects quality of life and a couple’s relationship. It also can reveal other conditions,” added Dr. Burté.
 

Spot and Assess

In terms of detecting the condition, the reference tool is the self-assessed Female Sexual Function Index, which comprises 19 questions covering six areas of sexual dysfunction: Desire, subjective arousal, lubrication, orgasm, satisfaction, and pain or discomfort.

But it is also possible to use the Sexual Complaints Screener for Women that evaluates sexual health over the past 6 months, explains Dr. Burté. For example, the patient is asked if she has had a lack of or low interest in sex or sexual desire in the past 6 months and if this has been a problem. She is also asked if she has experienced any pain during or after sexual activity.

To understand the root cause of sexual dysfunction, clinicians need to investigate the patient’s sexual health and perform a medical assessment. It’s also essential to ask the patient about her previous sexual, medical, and psychological history and to evaluate the couple and contributory factors, such as stress, fatigue, etc. This approach is known as the biopsychosocial model.

Once the contributory factors have been determined, relevant information can be given to the patient about her specific sexual problem, and the most suitable therapeutic approaches can be discussed with her.
 

Which Treatment Pathway?

Some problems may be improved with simple advice and lifestyle changes, but sex therapy and medication are options in other cases, explained the two doctors. “Since the causes of sexual dysfunction in women are mostly multifactorial, an integrative approach is needed,” said Dr. Burté.

The two main types of therapy that might be proposed for sexual dysfunction are sex therapies with cognitive behavioral therapy (CBT) and certain medicines being used as first-line treatment.

Using CBT in sexology requires patients and therapists to look past prejudices, preconceived ideas, and dysfunctional patterns and learn new behavioral, cognitive, and attentional strategies in terms of sexual health, regardless of whether an individual or couple is being treated.
 

Which Medicines?

Vasoactive drugs such as phosphodiesterase 5 inhibitors and prostaglandin have produced disappointing results. Drugs that act on the central nervous system to stimulate sexual desire, such as bremelanotide and flibanserin, don’t have marketing authorization in France due to their “insufficient” risk-benefit ratio.

However, topical hormone treatments (such as estrogen and dehydroepiandrosterone) are often used, particularly for cases of recurrent cystitis, in postmenopausal women and to treat urinary incontinence. “These topical treatments are very effective and can really change the life of a woman who no longer has a sex life because she is in discomfort and simply has dryness of the vulva and vagina,” said Dr. Burté, who recommends prescribing creams, which are better tolerated than pessaries.

General hormone treatments, hormone replacement therapy (HRT), and tibolone are prescribed to postmenopausal women.

Another option not yet authorized in France is testosterone because sexual desire depends on this hormone. An international consensus (2019, 10 learned societies) and recommendations made by the International Society for the Study of Women’s Sexual Health advise treatment with testosterone in the postmenopausal period, with or without HRT. The dose prescribed is a 10th of the male dose administered subcutaneously (300 µ/d) once a woman›s blood testosterone level has been determined to make sure there is an actual deficiency and to restore her testosterone to near premenopausal levels.

Both doctors indicated that having the chance to work with other doctors as part of a network is essential, especially with a sexual health specialist, if necessary.

Dr. Burté reported no conflicts of interest regarding the content of this article. Dr. Methorst reported relationships with several pharmaceutical laboratories.

This article was translated from the Medscape French edition.

TOPLINE:

Pregnancy weight gain is lower in women with a history of gastric bypass or sleeve gastrectomy than in those without such a history, especially when the interval between surgery and conception is shorter, new data suggest.

METHODOLOGY:

• Using Swedish national registers, researchers investigated the association of pregnancy weight gain with  history in 12,776 pregnancies — 6388 in women with a history of bariatric surgery and 6388 in women without such a history.
• Pregnancies were propensity score matched to patients’ early-pregnancy body mass index (BMI), prepregnancy diabetes, , smoking status, education, height, country of birth, and delivery year.
• Post-gastric bypass pregnancies were matched to post-sleeve gastrectomy pregnancies using the same matching strategy.
• Time from surgery to conception was also assessed.

TAKEAWAY:

• Across all early-pregnancy BMI strata, women with a history of bariatric surgery had lower pregnancy weight gain than matched controls.
• The magnitude of difference was largest for women with normal weight or overweight early-pregnancy BMI status (adjusted mean difference in z score, −0.33), which then decreased stepwise within the  subclasses (−0.21, −0.16, and −0.08 for obesity classes I, II, and III, respectively).
• Pregnancy weight gain did not differ by surgery type, but lower pregnancy weight gain was associated with a shorter surgery-to-conception interval (particularly within 1 year) or lower surgery-to-conception weight loss.

IN PRACTICE:

“The highest proportion of weight gain below the recommendations was found among women with a normal weight status. Hence, clinical attention to women with history of bariatric surgery and a normal weight status in early pregnancy might be warranted,” the authors advised.

SOURCE:

The study, with the first author Huiling Xu, MD, MSc, Karolinska Institutet, Stockholm, Sweden, was published online in JAMA Network Open.

LIMITATIONS:

Despite rigorous matching, residual confounding was possible. The sample size was limited for some subgroups, possibly affecting statistical power. Although the study provides an overview of pregnancy outcomes within surgery-to-conception interval and pregnancy weight gain z scores, a more in-depth investigation is needed to understand the associations among bariatric surgery, pregnancy weight gain, and pregnancy outcomes.

DISCLOSURES:

Research for this study was supported by the Swedish Research Council for Health, Working Life and Welfare, and the Swedish Research Council. The authors have no relevant disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

Pregnancy weight gain is lower in women with a history of gastric bypass or sleeve gastrectomy than in those without such a history, especially when the interval between surgery and conception is shorter, new data suggest.

METHODOLOGY:

• Using Swedish national registers, researchers investigated the association of pregnancy weight gain with  history in 12,776 pregnancies — 6388 in women with a history of bariatric surgery and 6388 in women without such a history.
• Pregnancies were propensity score matched to patients’ early-pregnancy body mass index (BMI), prepregnancy diabetes, , smoking status, education, height, country of birth, and delivery year.
• Post-gastric bypass pregnancies were matched to post-sleeve gastrectomy pregnancies using the same matching strategy.
• Time from surgery to conception was also assessed.

TAKEAWAY:

• Across all early-pregnancy BMI strata, women with a history of bariatric surgery had lower pregnancy weight gain than matched controls.
• The magnitude of difference was largest for women with normal weight or overweight early-pregnancy BMI status (adjusted mean difference in z score, −0.33), which then decreased stepwise within the  subclasses (−0.21, −0.16, and −0.08 for obesity classes I, II, and III, respectively).
• Pregnancy weight gain did not differ by surgery type, but lower pregnancy weight gain was associated with a shorter surgery-to-conception interval (particularly within 1 year) or lower surgery-to-conception weight loss.

IN PRACTICE:

“The highest proportion of weight gain below the recommendations was found among women with a normal weight status. Hence, clinical attention to women with history of bariatric surgery and a normal weight status in early pregnancy might be warranted,” the authors advised.

SOURCE:

The study, with the first author Huiling Xu, MD, MSc, Karolinska Institutet, Stockholm, Sweden, was published online in JAMA Network Open.

LIMITATIONS:

Despite rigorous matching, residual confounding was possible. The sample size was limited for some subgroups, possibly affecting statistical power. Although the study provides an overview of pregnancy outcomes within surgery-to-conception interval and pregnancy weight gain z scores, a more in-depth investigation is needed to understand the associations among bariatric surgery, pregnancy weight gain, and pregnancy outcomes.

DISCLOSURES:

Research for this study was supported by the Swedish Research Council for Health, Working Life and Welfare, and the Swedish Research Council. The authors have no relevant disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

Pregnancy weight gain is lower in women with a history of gastric bypass or sleeve gastrectomy than in those without such a history, especially when the interval between surgery and conception is shorter, new data suggest.

METHODOLOGY:

• Using Swedish national registers, researchers investigated the association of pregnancy weight gain with  history in 12,776 pregnancies — 6388 in women with a history of bariatric surgery and 6388 in women without such a history.
• Pregnancies were propensity score matched to patients’ early-pregnancy body mass index (BMI), prepregnancy diabetes, , smoking status, education, height, country of birth, and delivery year.
• Post-gastric bypass pregnancies were matched to post-sleeve gastrectomy pregnancies using the same matching strategy.
• Time from surgery to conception was also assessed.

TAKEAWAY:

• Across all early-pregnancy BMI strata, women with a history of bariatric surgery had lower pregnancy weight gain than matched controls.
• The magnitude of difference was largest for women with normal weight or overweight early-pregnancy BMI status (adjusted mean difference in z score, −0.33), which then decreased stepwise within the  subclasses (−0.21, −0.16, and −0.08 for obesity classes I, II, and III, respectively).
• Pregnancy weight gain did not differ by surgery type, but lower pregnancy weight gain was associated with a shorter surgery-to-conception interval (particularly within 1 year) or lower surgery-to-conception weight loss.

IN PRACTICE:

“The highest proportion of weight gain below the recommendations was found among women with a normal weight status. Hence, clinical attention to women with history of bariatric surgery and a normal weight status in early pregnancy might be warranted,” the authors advised.

SOURCE:

The study, with the first author Huiling Xu, MD, MSc, Karolinska Institutet, Stockholm, Sweden, was published online in JAMA Network Open.

LIMITATIONS:

Despite rigorous matching, residual confounding was possible. The sample size was limited for some subgroups, possibly affecting statistical power. Although the study provides an overview of pregnancy outcomes within surgery-to-conception interval and pregnancy weight gain z scores, a more in-depth investigation is needed to understand the associations among bariatric surgery, pregnancy weight gain, and pregnancy outcomes.

DISCLOSURES:

Research for this study was supported by the Swedish Research Council for Health, Working Life and Welfare, and the Swedish Research Council. The authors have no relevant disclosures.

A version of this article appeared on Medscape.com.