Preterm Birth

Approximately one-quarter of mothers with diabetes failed induction of labor, and this failure was associated with a range of adverse outcomes for mothers and infants, based on data from more than 2,000 individuals.

Uncontrolled diabetes remains a risk factor for cesarean delivery, Ali Alhousseini, MD, of Corewell Health East, Dearborn, Michigan, and colleagues wrote in a study presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists.

“Identifying and stratifying associated risk factors for failed induction of labor [IOL] may improve counseling and intrapartum care,” the researchers wrote in their abstract.

The researchers reviewed data from 2,172 mothers with diabetes who underwent IOL at a single university medical center between January 2013 and December 2021. They examined a range of maternal characteristics including age, ethnicity, gestational age, medical comorbidities, insulin administration, parity, and health insurance.

A total of 567 mothers with diabetes (26.1%) failed IOL and underwent cesarean delivery.

Overall, failed IOL was significantly associated with nulliparity (P = .0001), as well as preexisting diabetes compared with gestational diabetes, diabetes control with insulin, maternal essential hypertension, preeclampsia, and polyhydramnios (P = .001 for all). Other factors significantly associated with failed IOL included prenatal diagnosis of fetal growth restriction (P = .008), and placental abnormalities (P = .027).

Neonatal factors of weight, large for gestational age, head circumference, and height were not significantly associated with failed IOL (P > .05 for all).

As for neonatal outcomes, failed IOL was significantly associated with admission to neonatal intensive care unit, hyperbilirubinemia, and longer hospital stay (P = .001 for all). Failed IOL was significantly associated with lower 1-minute APGAR scores, but not with lower 5-minute APGAR scores, the researchers noted (P = .033 for 1-minute score). No association was noted between failed IOL and neonatal readmission, lower umbilical cord pH value, or maternal ethnicity.

The findings were limited by the retrospective design, but data analysis is ongoing, Dr. Alhousseini said. The researchers are continuing to assess the roles not only of optimal glucose control, but other maternal factors in improving maternal and neonatal outcomes, he said.
 

Data Add to Awareness of Risk Factors

The current study is important because of the increasing incidence of diabetes and the need to examine associated risk factors in pregnancy, Michael Richley, MD, a maternal fetal medicine physician at the University of Washington, Seattle, said in an interview. “The average age of onset of diabetes is becoming younger and type 2 diabetes in pregnancy is an increasingly common diagnosis,” said Dr. Richley, who was not involved in the study.  

The increase in both maternal and neonatal adverse outcomes is expected given the risk factors identified in the study, said Dr. Richley. “The patients with diabetes also were sicker at baseline, with hypertensive disorders, growth restriction, and pregestational diabetes,” he noted.

The study findings support data from previous research, Dr. Richley said. The message to clinicians is that patients with diabetes not only have an increased risk of needing a cesarean delivery but also have an increased risk of poor outcomes if a cesarean delivery is needed, he said.

Although a prospective study would be useful to show causality as opposed to just an association, such a study is challenging in this patient population given the limitations of conducting research on labor and delivery, he said.

The study received no outside funding. The researchers and Dr. Richley had no financial conflicts to disclose.

Approximately one-quarter of mothers with diabetes failed induction of labor, and this failure was associated with a range of adverse outcomes for mothers and infants, based on data from more than 2,000 individuals.

Uncontrolled diabetes remains a risk factor for cesarean delivery, Ali Alhousseini, MD, of Corewell Health East, Dearborn, Michigan, and colleagues wrote in a study presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists.

“Identifying and stratifying associated risk factors for failed induction of labor [IOL] may improve counseling and intrapartum care,” the researchers wrote in their abstract.

The researchers reviewed data from 2,172 mothers with diabetes who underwent IOL at a single university medical center between January 2013 and December 2021. They examined a range of maternal characteristics including age, ethnicity, gestational age, medical comorbidities, insulin administration, parity, and health insurance.

A total of 567 mothers with diabetes (26.1%) failed IOL and underwent cesarean delivery.

Overall, failed IOL was significantly associated with nulliparity (P = .0001), as well as preexisting diabetes compared with gestational diabetes, diabetes control with insulin, maternal essential hypertension, preeclampsia, and polyhydramnios (P = .001 for all). Other factors significantly associated with failed IOL included prenatal diagnosis of fetal growth restriction (P = .008), and placental abnormalities (P = .027).

Neonatal factors of weight, large for gestational age, head circumference, and height were not significantly associated with failed IOL (P > .05 for all).

As for neonatal outcomes, failed IOL was significantly associated with admission to neonatal intensive care unit, hyperbilirubinemia, and longer hospital stay (P = .001 for all). Failed IOL was significantly associated with lower 1-minute APGAR scores, but not with lower 5-minute APGAR scores, the researchers noted (P = .033 for 1-minute score). No association was noted between failed IOL and neonatal readmission, lower umbilical cord pH value, or maternal ethnicity.

The findings were limited by the retrospective design, but data analysis is ongoing, Dr. Alhousseini said. The researchers are continuing to assess the roles not only of optimal glucose control, but other maternal factors in improving maternal and neonatal outcomes, he said.
 

Data Add to Awareness of Risk Factors

The current study is important because of the increasing incidence of diabetes and the need to examine associated risk factors in pregnancy, Michael Richley, MD, a maternal fetal medicine physician at the University of Washington, Seattle, said in an interview. “The average age of onset of diabetes is becoming younger and type 2 diabetes in pregnancy is an increasingly common diagnosis,” said Dr. Richley, who was not involved in the study.  

The increase in both maternal and neonatal adverse outcomes is expected given the risk factors identified in the study, said Dr. Richley. “The patients with diabetes also were sicker at baseline, with hypertensive disorders, growth restriction, and pregestational diabetes,” he noted.

The study findings support data from previous research, Dr. Richley said. The message to clinicians is that patients with diabetes not only have an increased risk of needing a cesarean delivery but also have an increased risk of poor outcomes if a cesarean delivery is needed, he said.

Although a prospective study would be useful to show causality as opposed to just an association, such a study is challenging in this patient population given the limitations of conducting research on labor and delivery, he said.

The study received no outside funding. The researchers and Dr. Richley had no financial conflicts to disclose.

Approximately one-quarter of mothers with diabetes failed induction of labor, and this failure was associated with a range of adverse outcomes for mothers and infants, based on data from more than 2,000 individuals.

Uncontrolled diabetes remains a risk factor for cesarean delivery, Ali Alhousseini, MD, of Corewell Health East, Dearborn, Michigan, and colleagues wrote in a study presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists.

“Identifying and stratifying associated risk factors for failed induction of labor [IOL] may improve counseling and intrapartum care,” the researchers wrote in their abstract.

The researchers reviewed data from 2,172 mothers with diabetes who underwent IOL at a single university medical center between January 2013 and December 2021. They examined a range of maternal characteristics including age, ethnicity, gestational age, medical comorbidities, insulin administration, parity, and health insurance.

A total of 567 mothers with diabetes (26.1%) failed IOL and underwent cesarean delivery.

Overall, failed IOL was significantly associated with nulliparity (P = .0001), as well as preexisting diabetes compared with gestational diabetes, diabetes control with insulin, maternal essential hypertension, preeclampsia, and polyhydramnios (P = .001 for all). Other factors significantly associated with failed IOL included prenatal diagnosis of fetal growth restriction (P = .008), and placental abnormalities (P = .027).

Neonatal factors of weight, large for gestational age, head circumference, and height were not significantly associated with failed IOL (P > .05 for all).

As for neonatal outcomes, failed IOL was significantly associated with admission to neonatal intensive care unit, hyperbilirubinemia, and longer hospital stay (P = .001 for all). Failed IOL was significantly associated with lower 1-minute APGAR scores, but not with lower 5-minute APGAR scores, the researchers noted (P = .033 for 1-minute score). No association was noted between failed IOL and neonatal readmission, lower umbilical cord pH value, or maternal ethnicity.

The findings were limited by the retrospective design, but data analysis is ongoing, Dr. Alhousseini said. The researchers are continuing to assess the roles not only of optimal glucose control, but other maternal factors in improving maternal and neonatal outcomes, he said.
 

Data Add to Awareness of Risk Factors

The current study is important because of the increasing incidence of diabetes and the need to examine associated risk factors in pregnancy, Michael Richley, MD, a maternal fetal medicine physician at the University of Washington, Seattle, said in an interview. “The average age of onset of diabetes is becoming younger and type 2 diabetes in pregnancy is an increasingly common diagnosis,” said Dr. Richley, who was not involved in the study.  

The increase in both maternal and neonatal adverse outcomes is expected given the risk factors identified in the study, said Dr. Richley. “The patients with diabetes also were sicker at baseline, with hypertensive disorders, growth restriction, and pregestational diabetes,” he noted.

The study findings support data from previous research, Dr. Richley said. The message to clinicians is that patients with diabetes not only have an increased risk of needing a cesarean delivery but also have an increased risk of poor outcomes if a cesarean delivery is needed, he said.

Although a prospective study would be useful to show causality as opposed to just an association, such a study is challenging in this patient population given the limitations of conducting research on labor and delivery, he said.

The study received no outside funding. The researchers and Dr. Richley had no financial conflicts to disclose.

Five experts discussed research that they considered to be highlights of the European Society of Medical Oncology (ESMO) Breast Cancer annual congress during a “Key Takeaways” session at the meeting.

Among the topics the speakers addressed were breast cancer prevention, early breast cancer, advanced breast cancer, and supportive care.

In recent years, the way clinicians look at carcinogenesis in breast cancer has changed, and many new targets for potential early detection and prevention have emerged, said Suzette Delaloge, MD, of Gustave Roussy, Paris, France, in her presentation at the meeting.

Instant risk assessment at different time points could potentially intercept cancer among high-risk individuals, she said.

A study by Mikael Eriksson, PhD, and colleagues focused on external validation of the Profound AI tool to identify breast cancer risk in the general population. The researchers showed an area under the curve of 0.72 in their AI risk model, which has the potential to be clinically meaningful, although it must be prospectively validated, Dr. Delaloge said in her presentation.

She also reviewed two studies on the use of genes to further refine breast cancer risk among carriers. One of these, a prospective study presented in a session by Kelly-Anne Phillips, MD, of Peter MacCallum Cancer Center, Melbourne, Australia, used the CANRISK online risk assessment tool and validated increased breast cancer risk in BRCA1 and BRCA2 carriers, with AUCs of 0.79 and 0.78, respectively. The other study, which was by Maria Rezqallah Aron, MD, and colleagues examined polygenic scores as a way to refine breast cancer risk stratification among carriers of the ALM and PALB2 genes as well. These genes might be useful in identifying individuals who could benefit from early intervention, including surgery, Dr. Delaloge said.
 

Translational Research

“Preparing my talk, I felt like a kid in a candy store,” because of the amount of new translational research presented, including several studies of endocrine treatment–based approaches to therapy, said Marleen Kok, MD, of the Netherlands Cancer Institute, Amsterdam.

In her presentation, Dr. Kok highlighted findings from an analysis of patients in the monarchE study (a trial of high-risk patients) showing a consistent improvement in invasive disease-free survival for the subset of patients with germline BRCA1 and BRCA2 mutations who received abemaciclib plus endocrine therapy.

The value of tumor-infiltrating lymphocytes (TILs) on patients who are not receiving chemotherapy is important because of the focus on prognosis, and prospective trials are underway, she said.

A poster on the impact of chemotherapy and stromal tumor-infiltrating lymphocytes (sTILs) in stage I triple-negative breast cancer showed no association between chemotherapy and better outcomes regardless of sTILs in patients who did and did not receive chemotherapy, which has implications for potential treatment sparing in this population, Dr. Kok noted.

Artificial Intelligence (AI) was the subject of several posters at the meeting, and Dr. Kok identified a multisite European study of an automated HER2 scoring system as notable for its size and accuracy. In the study, the accuracy among pathologists was much higher with the assistance of AI, she said. Using AI for more complex analysis has shown success, she said.

Dr. Kok ended her talk with a poster that surveyed breast cancer patients about their understanding of their disease. The results showed that less than half (44%) of patients reported that their healthcare providers had given them enough information to learn about their breast cancer type, and less than one third could recall terminology about biomarkers; the study is important because it shows that clinicians need to do better in explaining these terms to patients, Dr. Kok said.
 

Early Breast Cancer

Right-sizing therapy, meaning identifying the right treatment for every patient, is a key element of new research in early breast cancer, said Erika Hamilton, MD, of the Sarah Cannon Research Institute, Nashville, Tenn.

She highlighted safety and treatment duration updates from the NATALEE study, which compared adjuvant ribociclib plus nonsteroidal aromatase inhibitor (NSAI) to NSAI alone for ER+/HER2- breast cancer. The current analysis presented at the meeting showed significant benefits with the addition of ribociclib and no evidence of new safety signals or adverse event exacerbations at 3 years, she said. Dose modifications had no significant impact on efficacy, she added.

The findings of no impact of dose reduction on efficacy in both the NATALEE and monarchE studies provide important information on whether dosage can be reduced in patients, which will increase the odds that patients will tolerate extended therapy with good outcomes and stay on their prescribed therapies, Dr. Hamilton emphasized.

The CARABELA study, a phase 2 trial of neoadjuvant letrozole plus abemaciclib vs adriamycin and cyclophosphamide (AC), showed clinically similar response rates but did not meet its endpoint for residual cancer burden (RCB) scores. These data add to results from other studies and show that it is too soon to universally replace neoadjuvant chemotherapy as first-line treatment for highly proliferative ER+ breast cancer, Dr. Hamilton said in her presentation.
 

Advanced Breast Cancer

Take-home messages about advanced breast cancer include growing evidence for the potential benefits of antibody drug conjugates (ADCs), said Eva Ciruelos, MD, of University Hospital, Madrid, Spain. The TROPION-BREAST01 study, a phase 3 randomized trial, showed significant and clinically meaningful improvement in progression-free survival in patients with previously treated, inoperable, or metastatic HR+/HER2- breast cancer who received datopotamab deruxtecan (Dato-DXd) compared with those who received chemotherapy.

Data from an additional safety analysis were presented at the meeting; although Dato-DXd, a trophoblast cell-surface antigen 2 (TROP2)–directed antibody-drug conjugate, was well-tolerated, it is important to remain aware of toxicities, notably oral mucositis, which occurred in 55.6% of the patients in the study across all grades, and ocular surface toxicity, which occurred in 40% of patients across all grades, Dr. Ciruelos emphasized.

Key research in the area of advanced triple-negative breast cancer included data from the IMPASSION 132 study. This study is “specifically centered on early relapsers,” a population often excluded from other trials, Dr. Ciruelos said. In this study, patients with advanced triple-negative breast cancer were randomized to chemotherapy with or without atezolizumab, and the study showed no benefits with atezolizumab for overall survival, progression-free survival, or overall response rate, she said. “This is something to work with, because this is a very refractory population,” Dr. Ciruelos noted.

New immunotherapy combinations are needed to improve survival in advanced breast cancer patients, Dr. Ciruelos said. At the meeting, researchers presented interim data from a subset of patients in the MORPHEUS-pan breast cancer trial, a phase 1B/2 study involving multiple treatment combinations in locally advanced/metastatic breast cancer patients.

The interim analysis included 18-week data from triple-negative breast cancer patients and compared outcomes for patients randomized to atezolizumab with or without sacituzumab govitecan (SG).

The study was small, with only 31 patients in the combination arm and 11 controls, but the results were promising, with an overall response rate of 76.7% in the combination arm vs 66.7% in the control arm, Dr. Ciruelos said.

Supportive Care

Key supportive care takeaways included data on pregnancy in young breast cancer survivors and the safety of vaginal estrogen therapy in breast cancer patients with genitourinary symptoms, said Anne May, MD, of the University Medical Center Utrecht, Utrecht, Netherlands.

A study previously published in JAMA including nearly 5000 BRCA carriers who were diagnosed with invasive breast cancer at age 40 years or younger showed no association between pregnancy after breast cancer and adverse maternal or fetal outcomes, and pregnancy had no significant impact on overall survival. The authors presented new data on the safety of assisted reproductive techniques (ART) based on the 543 pregnancies in the original study, at the meeting. Of these, 436 conceived naturally, and 107 used ART. After a median of 9.1 years, ART had no effect on disease-free survival compared to natural conception (hazard ratio [HR], 0.64). Based on these findings, fertility preservation should be offered to all women who receive a breast cancer diagnosis and are interested in future fertility, Dr. May said.

Conceiving after breast cancer treatment and follow-up should not be contraindicated for young BRCA carriers, she added.No trial data are available for the effects of vaginal estrogen therapy (VET) on disease-free survival in breast cancer survivors with genitourinary symptoms caused by declining estrogen levels, Dr. May said. However, researchers in France and Switzerland conducted an emulation of a hypothetical target trial using data from the French National social security system for more than 130,000 individuals. Although VET therapy had no impact on disease-free survival in most breast cancer survivors overall, it did have a negative impact in a subset of patients with HR-positive and HR-negative tumors who were treated with aromatase inhibitors. The study was hypothetical, but important because the results suggest that clinicians can safely propose VTE to patients who report genitourinary symptoms after treatment for early-stage breast cancer with tamoxifen, but VTE should be avoided in patients treated with aromatase inhibitors, Dr. May said.

Dr. Delaloge disclosed research support to her institution from AstraZeneca, MSD, Bristol Myers Squibb, Sanofi, Taiho, Novartis, European Commission, INCa, Banque des Territoires, and Fondation Philanthropia. She also disclosed honoraria to her institution from AstraZeneca, Gilead, Novartis, Elsan, Besins, Sanofi, Exact Sciences, and Lilly, as well as travel support from Novartis.

Dr. Kok disclosed research funding from AstraZeneca, Bristol Myers Squibb, Daichi, and Roche, and advisory board membership/speaker’s fees from Alderaan Biotechnology, BIONTECH, Domain Therapeutics, AstraZeneca, Daichi, Bristol Myers Squibb, Gilead, Medscape, MSD, and Roche.

Dr. Hamilton disclosed a consulting advisory role (to her institution) for Accutar Biotechology, AstraZeneca, Daiichi Sankyo, Ellipses Pharma, Entos, Forsum Pharma, Gilead Sciences, Greenwich LifeSciences, Jazz Pharmaceuticals, Lilly, Medical Pharma Services, Mersana, Novartis, Olema Pharmaceuticals, Orum Therapeutics, Roche/Genentech, Stemline Therapeutics, ands others. She also disclosed contracted research/grant support to her institution only from Abbvie, Acerta Pharma, Accutar Biotechnology , ADC Therapeutics, AKESOBIO Australia , Amgen, Aravive, ArQule, Artios, Arvinas, AstraZeneca, AtlasMedx, BeiGene, Black Diamond and others.

Dr. Ciruelos disclosed serving as an external advisor for Roche, MSD, Gilead, AstraZeneca, Daichii Sankyo, Reveal Genomics, Pfizer, Novartis, and Lilly, as well as serving as a speaker for Roche, MSD, Gilead, AstraZeneca, Daichii Sankyo, Reveal Genomics, Pfizer, Novartis, Lilly, and Pierre Fabre. She also disclosed travel grants from Roche, Pfizer, and AstraZeneca, and research grants from Seagen and Roche.

Dr. May had no financial conflicts to disclose.

Five experts discussed research that they considered to be highlights of the European Society of Medical Oncology (ESMO) Breast Cancer annual congress during a “Key Takeaways” session at the meeting.

Among the topics the speakers addressed were breast cancer prevention, early breast cancer, advanced breast cancer, and supportive care.

In recent years, the way clinicians look at carcinogenesis in breast cancer has changed, and many new targets for potential early detection and prevention have emerged, said Suzette Delaloge, MD, of Gustave Roussy, Paris, France, in her presentation at the meeting.

Instant risk assessment at different time points could potentially intercept cancer among high-risk individuals, she said.

A study by Mikael Eriksson, PhD, and colleagues focused on external validation of the Profound AI tool to identify breast cancer risk in the general population. The researchers showed an area under the curve of 0.72 in their AI risk model, which has the potential to be clinically meaningful, although it must be prospectively validated, Dr. Delaloge said in her presentation.

She also reviewed two studies on the use of genes to further refine breast cancer risk among carriers. One of these, a prospective study presented in a session by Kelly-Anne Phillips, MD, of Peter MacCallum Cancer Center, Melbourne, Australia, used the CANRISK online risk assessment tool and validated increased breast cancer risk in BRCA1 and BRCA2 carriers, with AUCs of 0.79 and 0.78, respectively. The other study, which was by Maria Rezqallah Aron, MD, and colleagues examined polygenic scores as a way to refine breast cancer risk stratification among carriers of the ALM and PALB2 genes as well. These genes might be useful in identifying individuals who could benefit from early intervention, including surgery, Dr. Delaloge said.
 

Translational Research

“Preparing my talk, I felt like a kid in a candy store,” because of the amount of new translational research presented, including several studies of endocrine treatment–based approaches to therapy, said Marleen Kok, MD, of the Netherlands Cancer Institute, Amsterdam.

In her presentation, Dr. Kok highlighted findings from an analysis of patients in the monarchE study (a trial of high-risk patients) showing a consistent improvement in invasive disease-free survival for the subset of patients with germline BRCA1 and BRCA2 mutations who received abemaciclib plus endocrine therapy.

The value of tumor-infiltrating lymphocytes (TILs) on patients who are not receiving chemotherapy is important because of the focus on prognosis, and prospective trials are underway, she said.

A poster on the impact of chemotherapy and stromal tumor-infiltrating lymphocytes (sTILs) in stage I triple-negative breast cancer showed no association between chemotherapy and better outcomes regardless of sTILs in patients who did and did not receive chemotherapy, which has implications for potential treatment sparing in this population, Dr. Kok noted.

Artificial Intelligence (AI) was the subject of several posters at the meeting, and Dr. Kok identified a multisite European study of an automated HER2 scoring system as notable for its size and accuracy. In the study, the accuracy among pathologists was much higher with the assistance of AI, she said. Using AI for more complex analysis has shown success, she said.

Dr. Kok ended her talk with a poster that surveyed breast cancer patients about their understanding of their disease. The results showed that less than half (44%) of patients reported that their healthcare providers had given them enough information to learn about their breast cancer type, and less than one third could recall terminology about biomarkers; the study is important because it shows that clinicians need to do better in explaining these terms to patients, Dr. Kok said.
 

Early Breast Cancer

Right-sizing therapy, meaning identifying the right treatment for every patient, is a key element of new research in early breast cancer, said Erika Hamilton, MD, of the Sarah Cannon Research Institute, Nashville, Tenn.

She highlighted safety and treatment duration updates from the NATALEE study, which compared adjuvant ribociclib plus nonsteroidal aromatase inhibitor (NSAI) to NSAI alone for ER+/HER2- breast cancer. The current analysis presented at the meeting showed significant benefits with the addition of ribociclib and no evidence of new safety signals or adverse event exacerbations at 3 years, she said. Dose modifications had no significant impact on efficacy, she added.

The findings of no impact of dose reduction on efficacy in both the NATALEE and monarchE studies provide important information on whether dosage can be reduced in patients, which will increase the odds that patients will tolerate extended therapy with good outcomes and stay on their prescribed therapies, Dr. Hamilton emphasized.

The CARABELA study, a phase 2 trial of neoadjuvant letrozole plus abemaciclib vs adriamycin and cyclophosphamide (AC), showed clinically similar response rates but did not meet its endpoint for residual cancer burden (RCB) scores. These data add to results from other studies and show that it is too soon to universally replace neoadjuvant chemotherapy as first-line treatment for highly proliferative ER+ breast cancer, Dr. Hamilton said in her presentation.
 

Advanced Breast Cancer

Take-home messages about advanced breast cancer include growing evidence for the potential benefits of antibody drug conjugates (ADCs), said Eva Ciruelos, MD, of University Hospital, Madrid, Spain. The TROPION-BREAST01 study, a phase 3 randomized trial, showed significant and clinically meaningful improvement in progression-free survival in patients with previously treated, inoperable, or metastatic HR+/HER2- breast cancer who received datopotamab deruxtecan (Dato-DXd) compared with those who received chemotherapy.

Data from an additional safety analysis were presented at the meeting; although Dato-DXd, a trophoblast cell-surface antigen 2 (TROP2)–directed antibody-drug conjugate, was well-tolerated, it is important to remain aware of toxicities, notably oral mucositis, which occurred in 55.6% of the patients in the study across all grades, and ocular surface toxicity, which occurred in 40% of patients across all grades, Dr. Ciruelos emphasized.

Key research in the area of advanced triple-negative breast cancer included data from the IMPASSION 132 study. This study is “specifically centered on early relapsers,” a population often excluded from other trials, Dr. Ciruelos said. In this study, patients with advanced triple-negative breast cancer were randomized to chemotherapy with or without atezolizumab, and the study showed no benefits with atezolizumab for overall survival, progression-free survival, or overall response rate, she said. “This is something to work with, because this is a very refractory population,” Dr. Ciruelos noted.

New immunotherapy combinations are needed to improve survival in advanced breast cancer patients, Dr. Ciruelos said. At the meeting, researchers presented interim data from a subset of patients in the MORPHEUS-pan breast cancer trial, a phase 1B/2 study involving multiple treatment combinations in locally advanced/metastatic breast cancer patients.

The interim analysis included 18-week data from triple-negative breast cancer patients and compared outcomes for patients randomized to atezolizumab with or without sacituzumab govitecan (SG).

The study was small, with only 31 patients in the combination arm and 11 controls, but the results were promising, with an overall response rate of 76.7% in the combination arm vs 66.7% in the control arm, Dr. Ciruelos said.

Supportive Care

Key supportive care takeaways included data on pregnancy in young breast cancer survivors and the safety of vaginal estrogen therapy in breast cancer patients with genitourinary symptoms, said Anne May, MD, of the University Medical Center Utrecht, Utrecht, Netherlands.

A study previously published in JAMA including nearly 5000 BRCA carriers who were diagnosed with invasive breast cancer at age 40 years or younger showed no association between pregnancy after breast cancer and adverse maternal or fetal outcomes, and pregnancy had no significant impact on overall survival. The authors presented new data on the safety of assisted reproductive techniques (ART) based on the 543 pregnancies in the original study, at the meeting. Of these, 436 conceived naturally, and 107 used ART. After a median of 9.1 years, ART had no effect on disease-free survival compared to natural conception (hazard ratio [HR], 0.64). Based on these findings, fertility preservation should be offered to all women who receive a breast cancer diagnosis and are interested in future fertility, Dr. May said.

Conceiving after breast cancer treatment and follow-up should not be contraindicated for young BRCA carriers, she added.No trial data are available for the effects of vaginal estrogen therapy (VET) on disease-free survival in breast cancer survivors with genitourinary symptoms caused by declining estrogen levels, Dr. May said. However, researchers in France and Switzerland conducted an emulation of a hypothetical target trial using data from the French National social security system for more than 130,000 individuals. Although VET therapy had no impact on disease-free survival in most breast cancer survivors overall, it did have a negative impact in a subset of patients with HR-positive and HR-negative tumors who were treated with aromatase inhibitors. The study was hypothetical, but important because the results suggest that clinicians can safely propose VTE to patients who report genitourinary symptoms after treatment for early-stage breast cancer with tamoxifen, but VTE should be avoided in patients treated with aromatase inhibitors, Dr. May said.

Dr. Delaloge disclosed research support to her institution from AstraZeneca, MSD, Bristol Myers Squibb, Sanofi, Taiho, Novartis, European Commission, INCa, Banque des Territoires, and Fondation Philanthropia. She also disclosed honoraria to her institution from AstraZeneca, Gilead, Novartis, Elsan, Besins, Sanofi, Exact Sciences, and Lilly, as well as travel support from Novartis.

Dr. Kok disclosed research funding from AstraZeneca, Bristol Myers Squibb, Daichi, and Roche, and advisory board membership/speaker’s fees from Alderaan Biotechnology, BIONTECH, Domain Therapeutics, AstraZeneca, Daichi, Bristol Myers Squibb, Gilead, Medscape, MSD, and Roche.

Dr. Hamilton disclosed a consulting advisory role (to her institution) for Accutar Biotechology, AstraZeneca, Daiichi Sankyo, Ellipses Pharma, Entos, Forsum Pharma, Gilead Sciences, Greenwich LifeSciences, Jazz Pharmaceuticals, Lilly, Medical Pharma Services, Mersana, Novartis, Olema Pharmaceuticals, Orum Therapeutics, Roche/Genentech, Stemline Therapeutics, ands others. She also disclosed contracted research/grant support to her institution only from Abbvie, Acerta Pharma, Accutar Biotechnology , ADC Therapeutics, AKESOBIO Australia , Amgen, Aravive, ArQule, Artios, Arvinas, AstraZeneca, AtlasMedx, BeiGene, Black Diamond and others.

Dr. Ciruelos disclosed serving as an external advisor for Roche, MSD, Gilead, AstraZeneca, Daichii Sankyo, Reveal Genomics, Pfizer, Novartis, and Lilly, as well as serving as a speaker for Roche, MSD, Gilead, AstraZeneca, Daichii Sankyo, Reveal Genomics, Pfizer, Novartis, Lilly, and Pierre Fabre. She also disclosed travel grants from Roche, Pfizer, and AstraZeneca, and research grants from Seagen and Roche.

Dr. May had no financial conflicts to disclose.

Five experts discussed research that they considered to be highlights of the European Society of Medical Oncology (ESMO) Breast Cancer annual congress during a “Key Takeaways” session at the meeting.

Among the topics the speakers addressed were breast cancer prevention, early breast cancer, advanced breast cancer, and supportive care.

In recent years, the way clinicians look at carcinogenesis in breast cancer has changed, and many new targets for potential early detection and prevention have emerged, said Suzette Delaloge, MD, of Gustave Roussy, Paris, France, in her presentation at the meeting.

Instant risk assessment at different time points could potentially intercept cancer among high-risk individuals, she said.

A study by Mikael Eriksson, PhD, and colleagues focused on external validation of the Profound AI tool to identify breast cancer risk in the general population. The researchers showed an area under the curve of 0.72 in their AI risk model, which has the potential to be clinically meaningful, although it must be prospectively validated, Dr. Delaloge said in her presentation.

She also reviewed two studies on the use of genes to further refine breast cancer risk among carriers. One of these, a prospective study presented in a session by Kelly-Anne Phillips, MD, of Peter MacCallum Cancer Center, Melbourne, Australia, used the CANRISK online risk assessment tool and validated increased breast cancer risk in BRCA1 and BRCA2 carriers, with AUCs of 0.79 and 0.78, respectively. The other study, which was by Maria Rezqallah Aron, MD, and colleagues examined polygenic scores as a way to refine breast cancer risk stratification among carriers of the ALM and PALB2 genes as well. These genes might be useful in identifying individuals who could benefit from early intervention, including surgery, Dr. Delaloge said.
 

Translational Research

“Preparing my talk, I felt like a kid in a candy store,” because of the amount of new translational research presented, including several studies of endocrine treatment–based approaches to therapy, said Marleen Kok, MD, of the Netherlands Cancer Institute, Amsterdam.

In her presentation, Dr. Kok highlighted findings from an analysis of patients in the monarchE study (a trial of high-risk patients) showing a consistent improvement in invasive disease-free survival for the subset of patients with germline BRCA1 and BRCA2 mutations who received abemaciclib plus endocrine therapy.

The value of tumor-infiltrating lymphocytes (TILs) on patients who are not receiving chemotherapy is important because of the focus on prognosis, and prospective trials are underway, she said.

A poster on the impact of chemotherapy and stromal tumor-infiltrating lymphocytes (sTILs) in stage I triple-negative breast cancer showed no association between chemotherapy and better outcomes regardless of sTILs in patients who did and did not receive chemotherapy, which has implications for potential treatment sparing in this population, Dr. Kok noted.

Artificial Intelligence (AI) was the subject of several posters at the meeting, and Dr. Kok identified a multisite European study of an automated HER2 scoring system as notable for its size and accuracy. In the study, the accuracy among pathologists was much higher with the assistance of AI, she said. Using AI for more complex analysis has shown success, she said.

Dr. Kok ended her talk with a poster that surveyed breast cancer patients about their understanding of their disease. The results showed that less than half (44%) of patients reported that their healthcare providers had given them enough information to learn about their breast cancer type, and less than one third could recall terminology about biomarkers; the study is important because it shows that clinicians need to do better in explaining these terms to patients, Dr. Kok said.
 

Early Breast Cancer

Right-sizing therapy, meaning identifying the right treatment for every patient, is a key element of new research in early breast cancer, said Erika Hamilton, MD, of the Sarah Cannon Research Institute, Nashville, Tenn.

She highlighted safety and treatment duration updates from the NATALEE study, which compared adjuvant ribociclib plus nonsteroidal aromatase inhibitor (NSAI) to NSAI alone for ER+/HER2- breast cancer. The current analysis presented at the meeting showed significant benefits with the addition of ribociclib and no evidence of new safety signals or adverse event exacerbations at 3 years, she said. Dose modifications had no significant impact on efficacy, she added.

The findings of no impact of dose reduction on efficacy in both the NATALEE and monarchE studies provide important information on whether dosage can be reduced in patients, which will increase the odds that patients will tolerate extended therapy with good outcomes and stay on their prescribed therapies, Dr. Hamilton emphasized.

The CARABELA study, a phase 2 trial of neoadjuvant letrozole plus abemaciclib vs adriamycin and cyclophosphamide (AC), showed clinically similar response rates but did not meet its endpoint for residual cancer burden (RCB) scores. These data add to results from other studies and show that it is too soon to universally replace neoadjuvant chemotherapy as first-line treatment for highly proliferative ER+ breast cancer, Dr. Hamilton said in her presentation.
 

Advanced Breast Cancer

Take-home messages about advanced breast cancer include growing evidence for the potential benefits of antibody drug conjugates (ADCs), said Eva Ciruelos, MD, of University Hospital, Madrid, Spain. The TROPION-BREAST01 study, a phase 3 randomized trial, showed significant and clinically meaningful improvement in progression-free survival in patients with previously treated, inoperable, or metastatic HR+/HER2- breast cancer who received datopotamab deruxtecan (Dato-DXd) compared with those who received chemotherapy.

Data from an additional safety analysis were presented at the meeting; although Dato-DXd, a trophoblast cell-surface antigen 2 (TROP2)–directed antibody-drug conjugate, was well-tolerated, it is important to remain aware of toxicities, notably oral mucositis, which occurred in 55.6% of the patients in the study across all grades, and ocular surface toxicity, which occurred in 40% of patients across all grades, Dr. Ciruelos emphasized.

Key research in the area of advanced triple-negative breast cancer included data from the IMPASSION 132 study. This study is “specifically centered on early relapsers,” a population often excluded from other trials, Dr. Ciruelos said. In this study, patients with advanced triple-negative breast cancer were randomized to chemotherapy with or without atezolizumab, and the study showed no benefits with atezolizumab for overall survival, progression-free survival, or overall response rate, she said. “This is something to work with, because this is a very refractory population,” Dr. Ciruelos noted.

New immunotherapy combinations are needed to improve survival in advanced breast cancer patients, Dr. Ciruelos said. At the meeting, researchers presented interim data from a subset of patients in the MORPHEUS-pan breast cancer trial, a phase 1B/2 study involving multiple treatment combinations in locally advanced/metastatic breast cancer patients.

The interim analysis included 18-week data from triple-negative breast cancer patients and compared outcomes for patients randomized to atezolizumab with or without sacituzumab govitecan (SG).

The study was small, with only 31 patients in the combination arm and 11 controls, but the results were promising, with an overall response rate of 76.7% in the combination arm vs 66.7% in the control arm, Dr. Ciruelos said.

Supportive Care

Key supportive care takeaways included data on pregnancy in young breast cancer survivors and the safety of vaginal estrogen therapy in breast cancer patients with genitourinary symptoms, said Anne May, MD, of the University Medical Center Utrecht, Utrecht, Netherlands.

A study previously published in JAMA including nearly 5000 BRCA carriers who were diagnosed with invasive breast cancer at age 40 years or younger showed no association between pregnancy after breast cancer and adverse maternal or fetal outcomes, and pregnancy had no significant impact on overall survival. The authors presented new data on the safety of assisted reproductive techniques (ART) based on the 543 pregnancies in the original study, at the meeting. Of these, 436 conceived naturally, and 107 used ART. After a median of 9.1 years, ART had no effect on disease-free survival compared to natural conception (hazard ratio [HR], 0.64). Based on these findings, fertility preservation should be offered to all women who receive a breast cancer diagnosis and are interested in future fertility, Dr. May said.

Conceiving after breast cancer treatment and follow-up should not be contraindicated for young BRCA carriers, she added.No trial data are available for the effects of vaginal estrogen therapy (VET) on disease-free survival in breast cancer survivors with genitourinary symptoms caused by declining estrogen levels, Dr. May said. However, researchers in France and Switzerland conducted an emulation of a hypothetical target trial using data from the French National social security system for more than 130,000 individuals. Although VET therapy had no impact on disease-free survival in most breast cancer survivors overall, it did have a negative impact in a subset of patients with HR-positive and HR-negative tumors who were treated with aromatase inhibitors. The study was hypothetical, but important because the results suggest that clinicians can safely propose VTE to patients who report genitourinary symptoms after treatment for early-stage breast cancer with tamoxifen, but VTE should be avoided in patients treated with aromatase inhibitors, Dr. May said.

Dr. Delaloge disclosed research support to her institution from AstraZeneca, MSD, Bristol Myers Squibb, Sanofi, Taiho, Novartis, European Commission, INCa, Banque des Territoires, and Fondation Philanthropia. She also disclosed honoraria to her institution from AstraZeneca, Gilead, Novartis, Elsan, Besins, Sanofi, Exact Sciences, and Lilly, as well as travel support from Novartis.

Dr. Kok disclosed research funding from AstraZeneca, Bristol Myers Squibb, Daichi, and Roche, and advisory board membership/speaker’s fees from Alderaan Biotechnology, BIONTECH, Domain Therapeutics, AstraZeneca, Daichi, Bristol Myers Squibb, Gilead, Medscape, MSD, and Roche.

Dr. Hamilton disclosed a consulting advisory role (to her institution) for Accutar Biotechology, AstraZeneca, Daiichi Sankyo, Ellipses Pharma, Entos, Forsum Pharma, Gilead Sciences, Greenwich LifeSciences, Jazz Pharmaceuticals, Lilly, Medical Pharma Services, Mersana, Novartis, Olema Pharmaceuticals, Orum Therapeutics, Roche/Genentech, Stemline Therapeutics, ands others. She also disclosed contracted research/grant support to her institution only from Abbvie, Acerta Pharma, Accutar Biotechnology , ADC Therapeutics, AKESOBIO Australia , Amgen, Aravive, ArQule, Artios, Arvinas, AstraZeneca, AtlasMedx, BeiGene, Black Diamond and others.

Dr. Ciruelos disclosed serving as an external advisor for Roche, MSD, Gilead, AstraZeneca, Daichii Sankyo, Reveal Genomics, Pfizer, Novartis, and Lilly, as well as serving as a speaker for Roche, MSD, Gilead, AstraZeneca, Daichii Sankyo, Reveal Genomics, Pfizer, Novartis, Lilly, and Pierre Fabre. She also disclosed travel grants from Roche, Pfizer, and AstraZeneca, and research grants from Seagen and Roche.

Dr. May had no financial conflicts to disclose.

The early cancellation of a trial in southern India suggests that the use of antenatal steroids to prevent respiratory complications after late-preterm birth — a recommended practice in the United States — may not be effective in the developing world.

As reported in Obstetrics & Gynecology, researchers led by Hilda Yenuberi, MD, of Christian Medical College, Vellore, Tamil Nadu, India, stopped the randomized, triple-blinded, placebo-controlled CLAP (Corticosteroids in Late Pregnancy) study at 70% enrollment. An interim analysis found no benefit from prescribing betamethasone vs placebo to women at risk of late-preterm delivery between 34 and 36 and 6/7 weeks of gestation (primary outcome of respiratory distress: 4.9% vs 4.8%, respectively, relative risk [RR], 1.03; 95% CI, 0.57-1.84; number needed to treat = 786).

“These findings may suggest differing efficacy of antenatal corticosteroids in developing countries compared with developed countries ... that should be considered when late-preterm antenatal corticosteroids are administered,” the researchers wrote.

The use of steroids in patients at risk of delivery before 34 weeks is widely accepted as a way to prevent neonatal respiratory distress, a common and potentially deadly condition in premature infants whose lungs are not fully developed. However, there’s debate over steroid treatment in women who are expected to deliver later than 34 weeks but still preterm.

As the study notes, “the American College of Obstetricians and Gynecologists recommends a single course of betamethasone for pregnant individuals at risk of delivering between 34 and 36 6/7 weeks of gestation on the basis of the ALPS (Antenatal Late Preterm Steroid) trial.”

But other randomized trials have reached different conclusions, and steroids are not without risks. Studies have linked prenatal steroids to neurosensory disorders in babies, meaning they’re more likely to need hearing aids and eyeglasses, said Kellie Murphy, MD, MSc, professor of obstetrics and gynecology, University of Toronto, Toronto, Ontario, Canada, in an interview. Dr. Murphy, who was not involved in the new trial, added that there are links between steroids and greater likelihood of poorer performance in school,

For the new study, conducted from 2020 to 2022 at Christian Medical College and Hospital in Vellore, India, researchers randomly assigned 423 patients to betamethasone (410 in the interim analysis; average age, 26.8 years) and 424 to placebo (415 in the interim analysis; average age, 26.2 years).

The average age of participants was 26.8 years. All were between 34 and 36 6/7 weeks of gestation and expected to give birth within the next week. A quarter of participants delivered at term, which the authors wrote “may have influenced the primary outcome.” The total number of neonates was 883, including 58 twin pregnancies.

There was no significant difference in respiratory distress between groups, “defined as need for oxygen or continuous positive airway pressure or mechanical ventilation for at least 2 hours in the first 72 hours of life.” There also were no significant differences in maternal outcomes such as chorioamnionitis or length of hospitalization or neonatal secondary outcomes such as transient tachypnea of the newborn, respiratory distress syndrome, necrotizing enterocolitis, sepsis, hyperbilirubinemia, stillbirth, and early neonatal death.

Serious adverse events occurred in four neonates but none were linked to the intervention.

The study doesn’t discuss cost, but a 2019 report suggests that use of betamethasone to prevent neonatal respiratory distress is cost-effective.

“Our findings are contradictory to those of a systematic review, the major contributor of which was the ALPS trial,” the authors of the new study reported. “The primary outcome of the ALPS trial, the composite of neonatal treatment in the first 72 hours, was significantly less in the group who received betamethasone (11.6%), compared with the placebo group (14.4%; relative risk [RR], 0.80; 95% CI, 0.66-0.97).”

The study authors, who didn’t respond to requests for comment, noted that their trial included twin pregnancies and patients with gestational diabetes; the ALPS trial did not.

Perinatologist Cynthia Gyamfi-Bannerman, MD, MS, chair and professor of Obstetrics, Gynecology, and Reproductive Sciences at the University of California,San Diego, and principal investigator of the ALPS study, said in an interview that the inclusion of twins in the new trial is “a fundamental flaw.”

“Because antenatal corticosteroids have not been shown to be useful in twins at any gestational age, it is not surprising that including twins likely moved the findings to the null in this study,” she said. “Twins were purposefully excluded from the ALPS trial for this reason.”

According to the new study, “the primary outcome among singleton neonates occurred in 4.8% (18/374) who received betamethasone and 5.1% (20/393) who received placebo (RR, 0.94; 95% CI, 0.51-1.75)

What should clinicians take from the study findings? In an accompanying commentary, Blair J. Wylie, MD, MPH, of Columbia University Medical Center, New York, NY, and Syed Asad Ali, MBBS, MPH, of Aga Khan University, Karachi, Pakistan, wrote that, “in settings similar to the US-based ALPS trial, the practice of administering a course of late-preterm antenatal corticosteroids should be continued, as espoused by our professional organizations.”

However, the new study suggests that “research in high-resource environments may not be generalizable to low-resource settings,” they write.

Neonatologist Elizabeth Asztalos, MD, MSc, an associate scientist with Sunnybrook Health Sciences Center in Toronto, Canada, said in an interview that she doesn’t worry about pregnant mothers not getting steroids later than 34 weeks. “We have tools in our armamentarium in the NICU setting to help babies if they need it,” said Dr. Asztalos, who didn’t take part in the new trial. “We can put them on CPAP if they have wet lung. If they have an element of respiratory distress, we can give them surfactants. These bigger babies have more ability to recover from all this compared to a baby who was born at 24, 25, 26 weeks.”

For her part, the University of Toronto’s Dr. Murphy said decision-making about late-preterm steroids is complicated. “You don’t want to miss the opportunity to give to provide benefits for the patients” via steroids, she said. “But on the flip side, it’s a double-edged sword. It’s not easy. It’s not straightforward.”

In the big picture, she said, “people need to be really clear why they’re giving an intervention and what they hope to achieve.”

Christian Medical College supported the study. The authors, Dr. Murphy, Dr. Asztalos, and commentary co-author Dr. Ali have no disclosures. Dr. Gyamfi-Bannerman discloses being principal investigator of the ALPS trial. Commentary co-author Dr. Wylie serves on the ultrasound quality assurance committee of a trial discussed in the commentary.

The early cancellation of a trial in southern India suggests that the use of antenatal steroids to prevent respiratory complications after late-preterm birth — a recommended practice in the United States — may not be effective in the developing world.

As reported in Obstetrics & Gynecology, researchers led by Hilda Yenuberi, MD, of Christian Medical College, Vellore, Tamil Nadu, India, stopped the randomized, triple-blinded, placebo-controlled CLAP (Corticosteroids in Late Pregnancy) study at 70% enrollment. An interim analysis found no benefit from prescribing betamethasone vs placebo to women at risk of late-preterm delivery between 34 and 36 and 6/7 weeks of gestation (primary outcome of respiratory distress: 4.9% vs 4.8%, respectively, relative risk [RR], 1.03; 95% CI, 0.57-1.84; number needed to treat = 786).

“These findings may suggest differing efficacy of antenatal corticosteroids in developing countries compared with developed countries ... that should be considered when late-preterm antenatal corticosteroids are administered,” the researchers wrote.

The use of steroids in patients at risk of delivery before 34 weeks is widely accepted as a way to prevent neonatal respiratory distress, a common and potentially deadly condition in premature infants whose lungs are not fully developed. However, there’s debate over steroid treatment in women who are expected to deliver later than 34 weeks but still preterm.

As the study notes, “the American College of Obstetricians and Gynecologists recommends a single course of betamethasone for pregnant individuals at risk of delivering between 34 and 36 6/7 weeks of gestation on the basis of the ALPS (Antenatal Late Preterm Steroid) trial.”

But other randomized trials have reached different conclusions, and steroids are not without risks. Studies have linked prenatal steroids to neurosensory disorders in babies, meaning they’re more likely to need hearing aids and eyeglasses, said Kellie Murphy, MD, MSc, professor of obstetrics and gynecology, University of Toronto, Toronto, Ontario, Canada, in an interview. Dr. Murphy, who was not involved in the new trial, added that there are links between steroids and greater likelihood of poorer performance in school,

For the new study, conducted from 2020 to 2022 at Christian Medical College and Hospital in Vellore, India, researchers randomly assigned 423 patients to betamethasone (410 in the interim analysis; average age, 26.8 years) and 424 to placebo (415 in the interim analysis; average age, 26.2 years).

The average age of participants was 26.8 years. All were between 34 and 36 6/7 weeks of gestation and expected to give birth within the next week. A quarter of participants delivered at term, which the authors wrote “may have influenced the primary outcome.” The total number of neonates was 883, including 58 twin pregnancies.

There was no significant difference in respiratory distress between groups, “defined as need for oxygen or continuous positive airway pressure or mechanical ventilation for at least 2 hours in the first 72 hours of life.” There also were no significant differences in maternal outcomes such as chorioamnionitis or length of hospitalization or neonatal secondary outcomes such as transient tachypnea of the newborn, respiratory distress syndrome, necrotizing enterocolitis, sepsis, hyperbilirubinemia, stillbirth, and early neonatal death.

Serious adverse events occurred in four neonates but none were linked to the intervention.

The study doesn’t discuss cost, but a 2019 report suggests that use of betamethasone to prevent neonatal respiratory distress is cost-effective.

“Our findings are contradictory to those of a systematic review, the major contributor of which was the ALPS trial,” the authors of the new study reported. “The primary outcome of the ALPS trial, the composite of neonatal treatment in the first 72 hours, was significantly less in the group who received betamethasone (11.6%), compared with the placebo group (14.4%; relative risk [RR], 0.80; 95% CI, 0.66-0.97).”

The study authors, who didn’t respond to requests for comment, noted that their trial included twin pregnancies and patients with gestational diabetes; the ALPS trial did not.

Perinatologist Cynthia Gyamfi-Bannerman, MD, MS, chair and professor of Obstetrics, Gynecology, and Reproductive Sciences at the University of California,San Diego, and principal investigator of the ALPS study, said in an interview that the inclusion of twins in the new trial is “a fundamental flaw.”

“Because antenatal corticosteroids have not been shown to be useful in twins at any gestational age, it is not surprising that including twins likely moved the findings to the null in this study,” she said. “Twins were purposefully excluded from the ALPS trial for this reason.”

According to the new study, “the primary outcome among singleton neonates occurred in 4.8% (18/374) who received betamethasone and 5.1% (20/393) who received placebo (RR, 0.94; 95% CI, 0.51-1.75)

What should clinicians take from the study findings? In an accompanying commentary, Blair J. Wylie, MD, MPH, of Columbia University Medical Center, New York, NY, and Syed Asad Ali, MBBS, MPH, of Aga Khan University, Karachi, Pakistan, wrote that, “in settings similar to the US-based ALPS trial, the practice of administering a course of late-preterm antenatal corticosteroids should be continued, as espoused by our professional organizations.”

However, the new study suggests that “research in high-resource environments may not be generalizable to low-resource settings,” they write.

Neonatologist Elizabeth Asztalos, MD, MSc, an associate scientist with Sunnybrook Health Sciences Center in Toronto, Canada, said in an interview that she doesn’t worry about pregnant mothers not getting steroids later than 34 weeks. “We have tools in our armamentarium in the NICU setting to help babies if they need it,” said Dr. Asztalos, who didn’t take part in the new trial. “We can put them on CPAP if they have wet lung. If they have an element of respiratory distress, we can give them surfactants. These bigger babies have more ability to recover from all this compared to a baby who was born at 24, 25, 26 weeks.”

For her part, the University of Toronto’s Dr. Murphy said decision-making about late-preterm steroids is complicated. “You don’t want to miss the opportunity to give to provide benefits for the patients” via steroids, she said. “But on the flip side, it’s a double-edged sword. It’s not easy. It’s not straightforward.”

In the big picture, she said, “people need to be really clear why they’re giving an intervention and what they hope to achieve.”

Christian Medical College supported the study. The authors, Dr. Murphy, Dr. Asztalos, and commentary co-author Dr. Ali have no disclosures. Dr. Gyamfi-Bannerman discloses being principal investigator of the ALPS trial. Commentary co-author Dr. Wylie serves on the ultrasound quality assurance committee of a trial discussed in the commentary.

The early cancellation of a trial in southern India suggests that the use of antenatal steroids to prevent respiratory complications after late-preterm birth — a recommended practice in the United States — may not be effective in the developing world.

As reported in Obstetrics & Gynecology, researchers led by Hilda Yenuberi, MD, of Christian Medical College, Vellore, Tamil Nadu, India, stopped the randomized, triple-blinded, placebo-controlled CLAP (Corticosteroids in Late Pregnancy) study at 70% enrollment. An interim analysis found no benefit from prescribing betamethasone vs placebo to women at risk of late-preterm delivery between 34 and 36 and 6/7 weeks of gestation (primary outcome of respiratory distress: 4.9% vs 4.8%, respectively, relative risk [RR], 1.03; 95% CI, 0.57-1.84; number needed to treat = 786).

“These findings may suggest differing efficacy of antenatal corticosteroids in developing countries compared with developed countries ... that should be considered when late-preterm antenatal corticosteroids are administered,” the researchers wrote.

The use of steroids in patients at risk of delivery before 34 weeks is widely accepted as a way to prevent neonatal respiratory distress, a common and potentially deadly condition in premature infants whose lungs are not fully developed. However, there’s debate over steroid treatment in women who are expected to deliver later than 34 weeks but still preterm.

As the study notes, “the American College of Obstetricians and Gynecologists recommends a single course of betamethasone for pregnant individuals at risk of delivering between 34 and 36 6/7 weeks of gestation on the basis of the ALPS (Antenatal Late Preterm Steroid) trial.”

But other randomized trials have reached different conclusions, and steroids are not without risks. Studies have linked prenatal steroids to neurosensory disorders in babies, meaning they’re more likely to need hearing aids and eyeglasses, said Kellie Murphy, MD, MSc, professor of obstetrics and gynecology, University of Toronto, Toronto, Ontario, Canada, in an interview. Dr. Murphy, who was not involved in the new trial, added that there are links between steroids and greater likelihood of poorer performance in school,

For the new study, conducted from 2020 to 2022 at Christian Medical College and Hospital in Vellore, India, researchers randomly assigned 423 patients to betamethasone (410 in the interim analysis; average age, 26.8 years) and 424 to placebo (415 in the interim analysis; average age, 26.2 years).

The average age of participants was 26.8 years. All were between 34 and 36 6/7 weeks of gestation and expected to give birth within the next week. A quarter of participants delivered at term, which the authors wrote “may have influenced the primary outcome.” The total number of neonates was 883, including 58 twin pregnancies.

There was no significant difference in respiratory distress between groups, “defined as need for oxygen or continuous positive airway pressure or mechanical ventilation for at least 2 hours in the first 72 hours of life.” There also were no significant differences in maternal outcomes such as chorioamnionitis or length of hospitalization or neonatal secondary outcomes such as transient tachypnea of the newborn, respiratory distress syndrome, necrotizing enterocolitis, sepsis, hyperbilirubinemia, stillbirth, and early neonatal death.

Serious adverse events occurred in four neonates but none were linked to the intervention.

The study doesn’t discuss cost, but a 2019 report suggests that use of betamethasone to prevent neonatal respiratory distress is cost-effective.

“Our findings are contradictory to those of a systematic review, the major contributor of which was the ALPS trial,” the authors of the new study reported. “The primary outcome of the ALPS trial, the composite of neonatal treatment in the first 72 hours, was significantly less in the group who received betamethasone (11.6%), compared with the placebo group (14.4%; relative risk [RR], 0.80; 95% CI, 0.66-0.97).”

The study authors, who didn’t respond to requests for comment, noted that their trial included twin pregnancies and patients with gestational diabetes; the ALPS trial did not.

Perinatologist Cynthia Gyamfi-Bannerman, MD, MS, chair and professor of Obstetrics, Gynecology, and Reproductive Sciences at the University of California,San Diego, and principal investigator of the ALPS study, said in an interview that the inclusion of twins in the new trial is “a fundamental flaw.”

“Because antenatal corticosteroids have not been shown to be useful in twins at any gestational age, it is not surprising that including twins likely moved the findings to the null in this study,” she said. “Twins were purposefully excluded from the ALPS trial for this reason.”

According to the new study, “the primary outcome among singleton neonates occurred in 4.8% (18/374) who received betamethasone and 5.1% (20/393) who received placebo (RR, 0.94; 95% CI, 0.51-1.75)

What should clinicians take from the study findings? In an accompanying commentary, Blair J. Wylie, MD, MPH, of Columbia University Medical Center, New York, NY, and Syed Asad Ali, MBBS, MPH, of Aga Khan University, Karachi, Pakistan, wrote that, “in settings similar to the US-based ALPS trial, the practice of administering a course of late-preterm antenatal corticosteroids should be continued, as espoused by our professional organizations.”

However, the new study suggests that “research in high-resource environments may not be generalizable to low-resource settings,” they write.

Neonatologist Elizabeth Asztalos, MD, MSc, an associate scientist with Sunnybrook Health Sciences Center in Toronto, Canada, said in an interview that she doesn’t worry about pregnant mothers not getting steroids later than 34 weeks. “We have tools in our armamentarium in the NICU setting to help babies if they need it,” said Dr. Asztalos, who didn’t take part in the new trial. “We can put them on CPAP if they have wet lung. If they have an element of respiratory distress, we can give them surfactants. These bigger babies have more ability to recover from all this compared to a baby who was born at 24, 25, 26 weeks.”

For her part, the University of Toronto’s Dr. Murphy said decision-making about late-preterm steroids is complicated. “You don’t want to miss the opportunity to give to provide benefits for the patients” via steroids, she said. “But on the flip side, it’s a double-edged sword. It’s not easy. It’s not straightforward.”

In the big picture, she said, “people need to be really clear why they’re giving an intervention and what they hope to achieve.”

Christian Medical College supported the study. The authors, Dr. Murphy, Dr. Asztalos, and commentary co-author Dr. Ali have no disclosures. Dr. Gyamfi-Bannerman discloses being principal investigator of the ALPS trial. Commentary co-author Dr. Wylie serves on the ultrasound quality assurance committee of a trial discussed in the commentary.

Safety concerns persist for out-of-hospital births in the United States with multiple potential risk factors and few safety requirements, according to a paper published in the American Journal of Obstetrics and Gynecology.

In 2022, the Centers for Disease Control and Prevention (CDC) reported the highest number of planned home births in 30 years. The numbers rose 12% from 2020 to 2021, the latest period for which complete data are available. Home births rose from 45,646 (1.26% of births) in 2020 to 51,642 (1.41% of births).

Amos Grünebaum, MD, and Frank A. Chervenak, MD, with Northwell Health, and the Department of Obstetrics and Gynecology, Lenox Hill Hospital, Zucker School of Medicine in New Hyde Park, New York, reviewed the latest safety data surrounding community births in the United States along with well-known perinatal risks and safety requirements for safe out-of-hospital births.

“Most planned home births continue to have one or more risk factors that are associated with an increase in adverse pregnancy outcomes,” they wrote.
 

Birth Certificate Data Analyzed

The researchers used the CDC birth certificate database and analyzed deliveries between 2016 and 2022 regarding the incidence of perinatal risks in community births. The risks included were prior cesarean, first baby, mother older than 35 years, twins, breech presentation, gestational age of less than 37 weeks or more than 41 weeks, newborn weight over 4,000 grams, adequacy of prenatal care, grand multiparity (5 or more prior pregnancies), and a prepregnancy body mass index of at least 35.

The incidence of perinatal risks for out-of-hospital births ranged individually from 0.2% to 28.54% among birthing center births and 0.32% to 24.4% for planned home births.

“The ACOG committee opinion on home births states that for every 1000 home births, 3.9 babies will die,” the authors noted, or about twice the risk of hospital births. The deaths are “potentially avoidable with easy access to an operating room,” they wrote.

Among the safety concerns for perinatal morbidity and mortality in community births, the authors cited the lack of:

• Appropriate patient selection for out-of-hospital births through standardized guidelines.
• Availability of a Certified Nurse Midwife, a Certified Midwife, or midwife whose education and licensure meet International Confederation of Midwives’ (ICM) Global Standards for Midwifery Education.
• Providers practicing obstetrics within an integrated and regulated health system with ready access and availability of board-certified obstetricians to provide consultation for qualified midwives.
• Standardized guidelines on when transport to a hospital is necessary.

“While prerequisites for a safe out-of-hospital delivery may be in place in other high-income countries, these prerequisites have not been actualized in the United States,” the authors wrote.

Incorporating Patient Preferences Into Delivery Models

Yalda Afshar, MD, PhD, maternal-fetal medicine subspecialist and a physician-scientist at UCLA Health in California, said obstetricians are responsible for offering the most evidence-based care to pregnant people.

“What this birth certificate data demonstrates,” she said, “is a tendency among birthing people to opt for out-of-hospital births, despite documented risks to both the pregnant person and the neonate. This underscores the need to persist in educating on risk stratification, risk reduction, and safe birthing practices, while also fostering innovation. Innovation should stem from our commitment to incorporate the preferences of pregnant people into our healthcare delivery model.”

Dr. Afshar, who was not part of the study, said clinicians should develop innovative ways to effectively meet the needs of pregnant patients while ensuring their safety and well-being.

“Ideally, we would establish safe environments within hospital systems and centers that emulate home-like birthing experiences, thereby mitigating risks for these families,” she said.

Though not explicitly stated in the data, she added, it is crucial to emphasize the need for continuous risk assessment throughout pregnancy and childbirth, “with a paramount focus on the safety of the pregnant individual.”

The authors and Dr. Afshar have no relevant financial disclosures.

Safety concerns persist for out-of-hospital births in the United States with multiple potential risk factors and few safety requirements, according to a paper published in the American Journal of Obstetrics and Gynecology.

In 2022, the Centers for Disease Control and Prevention (CDC) reported the highest number of planned home births in 30 years. The numbers rose 12% from 2020 to 2021, the latest period for which complete data are available. Home births rose from 45,646 (1.26% of births) in 2020 to 51,642 (1.41% of births).

Amos Grünebaum, MD, and Frank A. Chervenak, MD, with Northwell Health, and the Department of Obstetrics and Gynecology, Lenox Hill Hospital, Zucker School of Medicine in New Hyde Park, New York, reviewed the latest safety data surrounding community births in the United States along with well-known perinatal risks and safety requirements for safe out-of-hospital births.

“Most planned home births continue to have one or more risk factors that are associated with an increase in adverse pregnancy outcomes,” they wrote.
 

Birth Certificate Data Analyzed

The researchers used the CDC birth certificate database and analyzed deliveries between 2016 and 2022 regarding the incidence of perinatal risks in community births. The risks included were prior cesarean, first baby, mother older than 35 years, twins, breech presentation, gestational age of less than 37 weeks or more than 41 weeks, newborn weight over 4,000 grams, adequacy of prenatal care, grand multiparity (5 or more prior pregnancies), and a prepregnancy body mass index of at least 35.

The incidence of perinatal risks for out-of-hospital births ranged individually from 0.2% to 28.54% among birthing center births and 0.32% to 24.4% for planned home births.

“The ACOG committee opinion on home births states that for every 1000 home births, 3.9 babies will die,” the authors noted, or about twice the risk of hospital births. The deaths are “potentially avoidable with easy access to an operating room,” they wrote.

Among the safety concerns for perinatal morbidity and mortality in community births, the authors cited the lack of:

• Appropriate patient selection for out-of-hospital births through standardized guidelines.
• Availability of a Certified Nurse Midwife, a Certified Midwife, or midwife whose education and licensure meet International Confederation of Midwives’ (ICM) Global Standards for Midwifery Education.
• Providers practicing obstetrics within an integrated and regulated health system with ready access and availability of board-certified obstetricians to provide consultation for qualified midwives.
• Standardized guidelines on when transport to a hospital is necessary.

“While prerequisites for a safe out-of-hospital delivery may be in place in other high-income countries, these prerequisites have not been actualized in the United States,” the authors wrote.

Incorporating Patient Preferences Into Delivery Models

Yalda Afshar, MD, PhD, maternal-fetal medicine subspecialist and a physician-scientist at UCLA Health in California, said obstetricians are responsible for offering the most evidence-based care to pregnant people.

“What this birth certificate data demonstrates,” she said, “is a tendency among birthing people to opt for out-of-hospital births, despite documented risks to both the pregnant person and the neonate. This underscores the need to persist in educating on risk stratification, risk reduction, and safe birthing practices, while also fostering innovation. Innovation should stem from our commitment to incorporate the preferences of pregnant people into our healthcare delivery model.”

Dr. Afshar, who was not part of the study, said clinicians should develop innovative ways to effectively meet the needs of pregnant patients while ensuring their safety and well-being.

“Ideally, we would establish safe environments within hospital systems and centers that emulate home-like birthing experiences, thereby mitigating risks for these families,” she said.

Though not explicitly stated in the data, she added, it is crucial to emphasize the need for continuous risk assessment throughout pregnancy and childbirth, “with a paramount focus on the safety of the pregnant individual.”

The authors and Dr. Afshar have no relevant financial disclosures.

Safety concerns persist for out-of-hospital births in the United States with multiple potential risk factors and few safety requirements, according to a paper published in the American Journal of Obstetrics and Gynecology.

In 2022, the Centers for Disease Control and Prevention (CDC) reported the highest number of planned home births in 30 years. The numbers rose 12% from 2020 to 2021, the latest period for which complete data are available. Home births rose from 45,646 (1.26% of births) in 2020 to 51,642 (1.41% of births).

Amos Grünebaum, MD, and Frank A. Chervenak, MD, with Northwell Health, and the Department of Obstetrics and Gynecology, Lenox Hill Hospital, Zucker School of Medicine in New Hyde Park, New York, reviewed the latest safety data surrounding community births in the United States along with well-known perinatal risks and safety requirements for safe out-of-hospital births.

“Most planned home births continue to have one or more risk factors that are associated with an increase in adverse pregnancy outcomes,” they wrote.
 

Birth Certificate Data Analyzed

The researchers used the CDC birth certificate database and analyzed deliveries between 2016 and 2022 regarding the incidence of perinatal risks in community births. The risks included were prior cesarean, first baby, mother older than 35 years, twins, breech presentation, gestational age of less than 37 weeks or more than 41 weeks, newborn weight over 4,000 grams, adequacy of prenatal care, grand multiparity (5 or more prior pregnancies), and a prepregnancy body mass index of at least 35.

The incidence of perinatal risks for out-of-hospital births ranged individually from 0.2% to 28.54% among birthing center births and 0.32% to 24.4% for planned home births.

“The ACOG committee opinion on home births states that for every 1000 home births, 3.9 babies will die,” the authors noted, or about twice the risk of hospital births. The deaths are “potentially avoidable with easy access to an operating room,” they wrote.

Among the safety concerns for perinatal morbidity and mortality in community births, the authors cited the lack of:

• Appropriate patient selection for out-of-hospital births through standardized guidelines.
• Availability of a Certified Nurse Midwife, a Certified Midwife, or midwife whose education and licensure meet International Confederation of Midwives’ (ICM) Global Standards for Midwifery Education.
• Providers practicing obstetrics within an integrated and regulated health system with ready access and availability of board-certified obstetricians to provide consultation for qualified midwives.
• Standardized guidelines on when transport to a hospital is necessary.

“While prerequisites for a safe out-of-hospital delivery may be in place in other high-income countries, these prerequisites have not been actualized in the United States,” the authors wrote.

Incorporating Patient Preferences Into Delivery Models

Yalda Afshar, MD, PhD, maternal-fetal medicine subspecialist and a physician-scientist at UCLA Health in California, said obstetricians are responsible for offering the most evidence-based care to pregnant people.

“What this birth certificate data demonstrates,” she said, “is a tendency among birthing people to opt for out-of-hospital births, despite documented risks to both the pregnant person and the neonate. This underscores the need to persist in educating on risk stratification, risk reduction, and safe birthing practices, while also fostering innovation. Innovation should stem from our commitment to incorporate the preferences of pregnant people into our healthcare delivery model.”

Dr. Afshar, who was not part of the study, said clinicians should develop innovative ways to effectively meet the needs of pregnant patients while ensuring their safety and well-being.

“Ideally, we would establish safe environments within hospital systems and centers that emulate home-like birthing experiences, thereby mitigating risks for these families,” she said.

Though not explicitly stated in the data, she added, it is crucial to emphasize the need for continuous risk assessment throughout pregnancy and childbirth, “with a paramount focus on the safety of the pregnant individual.”

The authors and Dr. Afshar have no relevant financial disclosures.

TOPLINE:

A study comparing cervical pessary and vaginal progesterone for the prevention of preterm birth in women with a short cervix of ≤ 35 mm found no significant difference between the interventions for perinatal complications. Among women with a cervical length of ≤ 25 mm, however, pessaries appeared to be less effective at preventing spontaneous preterm birth and adverse outcomes, according to the researchers.

METHODOLOGY:

• Researchers conducted an open-label, randomized controlled trial at 20 hospitals and five obstetric ultrasound practices in the Netherlands.
• The study included 635 women with healthy singleton pregnancies between 18 and 22 weeks’ gestation and an asymptomatic short cervix of ≤ 35 mm. Participants had no history of spontaneous preterm birth.
• Women were randomly assigned to receive either an Arabin cervical pessary or 200 mg/d vaginal progesterone for ≤ 36 weeks of gestation.
• The investigators examined a composite measure of adverse perinatal outcomes, including  (grade, > 1), chronic lung disease,  (grade, III or IV),  (stage, > 1), , stillbirth, and death of the baby.

TAKEAWAY:

• Adverse perinatal outcomes occurred in 6% of each treatment group, and the rate of spontaneous preterm birth did not differ significantly between the groups.
• In a subgroup analysis of 131 patients with a cervical length of ≤ 25 mm, spontaneous preterm birth at < 28 weeks occurred more often in the pessary group (16% vs 4%).
• Adverse perinatal outcomes also seemed to occur more frequently in the pessary group (24% vs 12%; relative risk, 2.1 [95% CI, 0.95-4.60]), in the subgroup analysis, according to the researchers.

IN PRACTICE:

“Even though the study was not powered for the subgroup with a short cervix of ≤ 25 mm, results suggest that a cervical pessary should not be used as preventive treatment in this group,” the researchers wrote.

SOURCE:

The study was led by Charlotte E. van Dijk, MD, with Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands. It was published online in The BMJ.

LIMITATIONS:

The researchers were unable to mask the treatment groups, which could introduce bias. The study’s reliance on self-reported medication adherence in the progesterone group and a lack of extra training for pessary placement might have influenced the outcomes, the researchers noted.

DISCLOSURES:

The study was supported by Stichting Stoptevroegbevallen, a nonprofit research foundation. An author disclosed financial ties with Merck.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

A study comparing cervical pessary and vaginal progesterone for the prevention of preterm birth in women with a short cervix of ≤ 35 mm found no significant difference between the interventions for perinatal complications. Among women with a cervical length of ≤ 25 mm, however, pessaries appeared to be less effective at preventing spontaneous preterm birth and adverse outcomes, according to the researchers.

METHODOLOGY:

• Researchers conducted an open-label, randomized controlled trial at 20 hospitals and five obstetric ultrasound practices in the Netherlands.
• The study included 635 women with healthy singleton pregnancies between 18 and 22 weeks’ gestation and an asymptomatic short cervix of ≤ 35 mm. Participants had no history of spontaneous preterm birth.
• Women were randomly assigned to receive either an Arabin cervical pessary or 200 mg/d vaginal progesterone for ≤ 36 weeks of gestation.
• The investigators examined a composite measure of adverse perinatal outcomes, including  (grade, > 1), chronic lung disease,  (grade, III or IV),  (stage, > 1), , stillbirth, and death of the baby.

TAKEAWAY:

• Adverse perinatal outcomes occurred in 6% of each treatment group, and the rate of spontaneous preterm birth did not differ significantly between the groups.
• In a subgroup analysis of 131 patients with a cervical length of ≤ 25 mm, spontaneous preterm birth at < 28 weeks occurred more often in the pessary group (16% vs 4%).
• Adverse perinatal outcomes also seemed to occur more frequently in the pessary group (24% vs 12%; relative risk, 2.1 [95% CI, 0.95-4.60]), in the subgroup analysis, according to the researchers.

IN PRACTICE:

“Even though the study was not powered for the subgroup with a short cervix of ≤ 25 mm, results suggest that a cervical pessary should not be used as preventive treatment in this group,” the researchers wrote.

SOURCE:

The study was led by Charlotte E. van Dijk, MD, with Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands. It was published online in The BMJ.

LIMITATIONS:

The researchers were unable to mask the treatment groups, which could introduce bias. The study’s reliance on self-reported medication adherence in the progesterone group and a lack of extra training for pessary placement might have influenced the outcomes, the researchers noted.

DISCLOSURES:

The study was supported by Stichting Stoptevroegbevallen, a nonprofit research foundation. An author disclosed financial ties with Merck.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

A study comparing cervical pessary and vaginal progesterone for the prevention of preterm birth in women with a short cervix of ≤ 35 mm found no significant difference between the interventions for perinatal complications. Among women with a cervical length of ≤ 25 mm, however, pessaries appeared to be less effective at preventing spontaneous preterm birth and adverse outcomes, according to the researchers.

METHODOLOGY:

• Researchers conducted an open-label, randomized controlled trial at 20 hospitals and five obstetric ultrasound practices in the Netherlands.
• The study included 635 women with healthy singleton pregnancies between 18 and 22 weeks’ gestation and an asymptomatic short cervix of ≤ 35 mm. Participants had no history of spontaneous preterm birth.
• Women were randomly assigned to receive either an Arabin cervical pessary or 200 mg/d vaginal progesterone for ≤ 36 weeks of gestation.
• The investigators examined a composite measure of adverse perinatal outcomes, including  (grade, > 1), chronic lung disease,  (grade, III or IV),  (stage, > 1), , stillbirth, and death of the baby.

TAKEAWAY:

• Adverse perinatal outcomes occurred in 6% of each treatment group, and the rate of spontaneous preterm birth did not differ significantly between the groups.
• In a subgroup analysis of 131 patients with a cervical length of ≤ 25 mm, spontaneous preterm birth at < 28 weeks occurred more often in the pessary group (16% vs 4%).
• Adverse perinatal outcomes also seemed to occur more frequently in the pessary group (24% vs 12%; relative risk, 2.1 [95% CI, 0.95-4.60]), in the subgroup analysis, according to the researchers.

IN PRACTICE:

“Even though the study was not powered for the subgroup with a short cervix of ≤ 25 mm, results suggest that a cervical pessary should not be used as preventive treatment in this group,” the researchers wrote.

SOURCE:

The study was led by Charlotte E. van Dijk, MD, with Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands. It was published online in The BMJ.

LIMITATIONS:

The researchers were unable to mask the treatment groups, which could introduce bias. The study’s reliance on self-reported medication adherence in the progesterone group and a lack of extra training for pessary placement might have influenced the outcomes, the researchers noted.

DISCLOSURES:

The study was supported by Stichting Stoptevroegbevallen, a nonprofit research foundation. An author disclosed financial ties with Merck.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

A clinical trial of preterm infants with inguinal hernia found that performing repair after discharge from the neonatal intensive care unit (NICU) resulted in fewer adverse events than procedures prior to discharge.

METHODOLOGY:

• The study compared the safety of repair before discharge from the NICU with repair after discharge and post-55 weeks gestational plus chronological age (postmenstrual age).
• The study randomized 338 infants from 39 US hospitals to early or late repair; of the 320 infants who had the surgery, 86% were male, 30% were Black, and 59% were White.
• The primary outcome was the occurrence of at least one serious adverse event over the 10-month observation period, including apnea requiring respiratory intervention, intubation for more than 2 days, bradycardia requiring pharmacological intervention, or death.
• Secondary outcomes included a total number of days in the hospital, including the initial NICU stay after randomization, postoperative hospitalization, and any inpatient days due to hospital readmission over the course of the following 10-month period.

TAKEAWAY:

• Infants who underwent late repair had a lower probability of having at least one serious adverse event: 28% had at least one adverse event in the early group vs 18% in the late group.
• Infants in the late repair group had shorter stays in the NICU after randomization, as well as fewer hospital days following surgery.
• Late repair provided the greatest benefit to infants with a gestational age younger than 28 weeks and those who had bronchopulmonary dysplasia.
• Hernias resolved spontaneously in 4% of infants in the early repair group and 11% in the late group, which the authors said supports delaying hernia repair.

IN PRACTICE:

“The decision to treat the inguinal hernia with an early or late repair strategy likely does not influence the overall duration of the neonatal intensive care unit stay but may hasten the discharge by several days if later repair is chosen, which is likely important to parents and neonatologists.”

SOURCE:

The study was published online in JAMA. It was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Martin L. Blakely, MD, MS, from the Department of Surgery at the University of Texas Health Science Center, Houston, Texas, is the corresponding author.

LIMITATIONS:

This study had a modest sample size, an issue compounded by some subjects withdrawing from the trial. The randomization rate was lower than expected. The trial was also discontinued early due to meeting a prespecified stopping rule for effectiveness.

DISCLOSURES:

Study authors report grant support from the US Department of Defense, personal fees, author royalties, and institutional contracts with various companies including Medicem, Fresenius Kabi, Baxter, and Mead Johnson.

A version of this article appeared on Medscape.com.

TOPLINE:

A clinical trial of preterm infants with inguinal hernia found that performing repair after discharge from the neonatal intensive care unit (NICU) resulted in fewer adverse events than procedures prior to discharge.

METHODOLOGY:

• The study compared the safety of repair before discharge from the NICU with repair after discharge and post-55 weeks gestational plus chronological age (postmenstrual age).
• The study randomized 338 infants from 39 US hospitals to early or late repair; of the 320 infants who had the surgery, 86% were male, 30% were Black, and 59% were White.
• The primary outcome was the occurrence of at least one serious adverse event over the 10-month observation period, including apnea requiring respiratory intervention, intubation for more than 2 days, bradycardia requiring pharmacological intervention, or death.
• Secondary outcomes included a total number of days in the hospital, including the initial NICU stay after randomization, postoperative hospitalization, and any inpatient days due to hospital readmission over the course of the following 10-month period.

TAKEAWAY:

• Infants who underwent late repair had a lower probability of having at least one serious adverse event: 28% had at least one adverse event in the early group vs 18% in the late group.
• Infants in the late repair group had shorter stays in the NICU after randomization, as well as fewer hospital days following surgery.
• Late repair provided the greatest benefit to infants with a gestational age younger than 28 weeks and those who had bronchopulmonary dysplasia.
• Hernias resolved spontaneously in 4% of infants in the early repair group and 11% in the late group, which the authors said supports delaying hernia repair.

IN PRACTICE:

“The decision to treat the inguinal hernia with an early or late repair strategy likely does not influence the overall duration of the neonatal intensive care unit stay but may hasten the discharge by several days if later repair is chosen, which is likely important to parents and neonatologists.”

SOURCE:

The study was published online in JAMA. It was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Martin L. Blakely, MD, MS, from the Department of Surgery at the University of Texas Health Science Center, Houston, Texas, is the corresponding author.

LIMITATIONS:

This study had a modest sample size, an issue compounded by some subjects withdrawing from the trial. The randomization rate was lower than expected. The trial was also discontinued early due to meeting a prespecified stopping rule for effectiveness.

DISCLOSURES:

Study authors report grant support from the US Department of Defense, personal fees, author royalties, and institutional contracts with various companies including Medicem, Fresenius Kabi, Baxter, and Mead Johnson.

A version of this article appeared on Medscape.com.

TOPLINE:

A clinical trial of preterm infants with inguinal hernia found that performing repair after discharge from the neonatal intensive care unit (NICU) resulted in fewer adverse events than procedures prior to discharge.

METHODOLOGY:

• The study compared the safety of repair before discharge from the NICU with repair after discharge and post-55 weeks gestational plus chronological age (postmenstrual age).
• The study randomized 338 infants from 39 US hospitals to early or late repair; of the 320 infants who had the surgery, 86% were male, 30% were Black, and 59% were White.
• The primary outcome was the occurrence of at least one serious adverse event over the 10-month observation period, including apnea requiring respiratory intervention, intubation for more than 2 days, bradycardia requiring pharmacological intervention, or death.
• Secondary outcomes included a total number of days in the hospital, including the initial NICU stay after randomization, postoperative hospitalization, and any inpatient days due to hospital readmission over the course of the following 10-month period.

TAKEAWAY:

• Infants who underwent late repair had a lower probability of having at least one serious adverse event: 28% had at least one adverse event in the early group vs 18% in the late group.
• Infants in the late repair group had shorter stays in the NICU after randomization, as well as fewer hospital days following surgery.
• Late repair provided the greatest benefit to infants with a gestational age younger than 28 weeks and those who had bronchopulmonary dysplasia.
• Hernias resolved spontaneously in 4% of infants in the early repair group and 11% in the late group, which the authors said supports delaying hernia repair.

IN PRACTICE:

“The decision to treat the inguinal hernia with an early or late repair strategy likely does not influence the overall duration of the neonatal intensive care unit stay but may hasten the discharge by several days if later repair is chosen, which is likely important to parents and neonatologists.”

SOURCE:

The study was published online in JAMA. It was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Martin L. Blakely, MD, MS, from the Department of Surgery at the University of Texas Health Science Center, Houston, Texas, is the corresponding author.

LIMITATIONS:

This study had a modest sample size, an issue compounded by some subjects withdrawing from the trial. The randomization rate was lower than expected. The trial was also discontinued early due to meeting a prespecified stopping rule for effectiveness.

DISCLOSURES:

Study authors report grant support from the US Department of Defense, personal fees, author royalties, and institutional contracts with various companies including Medicem, Fresenius Kabi, Baxter, and Mead Johnson.

A version of this article appeared on Medscape.com.

A phase 3 trial of a maternal vaccine candidate for respiratory syncytial virus (RSV) has been stopped early because the risk for preterm births is higher in the candidate vaccine group than in the placebo group.

By the time enrollment was stopped on February 25, 2022 because of the safety signal of preterm birth, 5328 pregnant women had been vaccinated, about half of the intended 10,000 enrollees. Of these, 3557 received the candidate vaccine RSV prefusion F protein–based maternal vaccine, and another 1771 received a placebo.

Data from the trial, sponsored by GSK, were immediately made available when recruitment and vaccination were stopped, and investigation of the preterm birth risk followed. Results of that analysis, led by Ilse Dieussaert, IR, vice president for vaccine development at GSK in Wavre, Belgium, are published online on March 13 in The New England Journal of Medicine. 

“We have discontinued our work on this RSV maternal candidate vaccine, and we are closing out all ongoing trials with the exception of the MAT-015 follow-on study to monitor subsequent pregnancies,” a GSK spokesperson said in an interview.

The trial was conducted in pregnant women aged 18-49 years to assess the efficacy and safety of the vaccine. The women were randomly assigned 2:1 to receive the candidate vaccine or placebo between 24 and 34 weeks’ gestation.
 

Preterm Births

The primary outcomes were any or severe medically assessed RSV-associated lower respiratory tract infection in infants from birth to 6 months and safety in infants from birth to 12 months.

According to the data, preterm birth occurred in 6.8% of the infants in the vaccine group and in 4.9% of those in the placebo group (relative risk [RR], 1.37; 95% CI, 1.08-1.74; P = .01). Neonatal death occurred in 0.4% in the vaccine group and 0.2% in the placebo group (RR, 2.16; 95% CI, 0.62-7.56; P = .23).

To date, only one RSV vaccine (Abrysvo, Pfizer) has been approved for use during pregnancy to protect infants from RSV-associated lower respiratory tract infection.

“It was a very big deal that this trial was stopped, and the new candidate won’t get approval.” said Aaron E. Glatt, MD, chair of the Department of Medicine and chief of Infectious Diseases and Hospital Epidemiologist at Mount Sinai South Nassau in Oceanside, New York.
 

Only One RSV Vaccine Approved in Pregnancy

Dr. Glatt pointed out the GSK vaccine is like the maternal vaccine that did get approved. “The data clearly show that there was a slight but increased risk in preterm labor,” Dr. Glatt said, “and while not as clearly shown, there was an increase in neonatal death in the group of very small numbers, but any neonatal death is of concern.”

The implications were disturbing, he added, “You’re giving this vaccine to prevent neonatal death.” Though the Pfizer vaccine that was granted approval had a very slight increase in premature birth, the risk wasn’t statistically significant, he pointed out, “and it showed similar benefits in preventing neonatal illness, which can be fatal.”

Dr. Glatt said that there is still a lingering concern with the approved vaccine, and he explained that most clinicians will give it closer to the end of the recommended time window of 34 weeks. “This way, even if there is a slight increase in premature term labor, you’re probably not going to have a serious outcome because the baby will be far enough along.”

A difference in the incidence of preterm birth between the experimental vaccine and placebo groups was predominantly found in low- and middle-income countries, according to Dieussaert’s team, “where approximately 50% of the trial population was enrolled and where the medical need for maternal RSV vaccines is the greatest.”

The RR was 1.56 (95% CI, 1.17-2.10) for low- and middle-income countries and 1.04 (95% CI, 0.68-1.58) for high-income countries. 

“If a smaller percentage of participants from low- and middle-income countries had been enrolled in our trial, the RR for preterm birth in the vaccine group as compared with the placebo group might have been reduced in the overall trial population,” they reported.

The authors explained that the data do not reveal the cause of the higher risk for preterm birth in the vaccine group.

“We do not know what caused the signal,” the company’s spokesperson added. “GSK completed all the necessary steps of product development including preclinical toxicology studies and clinical studies in nonpregnant women prior to starting the studies in pregnant women. There were no safety signals identified in any of the earlier parts of the clinical testing. There have been no safety signals identified in the other phase 3 trials for this vaccine candidate.”

Researchers did not find a correlation between preterm births in the treatment vs control groups with gestational age at the time of vaccination or with particular vaccine clinical trial material lots, race, ethnicity, maternal smoking, alcohol consumption, body mass index, or time between study vaccination and delivery, the GSK spokesperson said.

The spokesperson noted that the halted vaccine is different from GSK’s currently approved adjuvanted RSV vaccine (Arexvy) for adults aged 60 years or older.

What’s Next for Other Vaccines

Maternal vaccines have been effective in preventing other diseases in infants, such as tetanus, influenza, and pertussis, but RSV is a very hard virus to make a vaccine for, Dr. Glatt shared.

The need is great to have more than one option for a maternal RSV vaccine, he added, to address any potential supply concerns.

“People have to realize how serious RSV can be in infants,” he said. “It can be a fatal disease. This can be a serious illness even in healthy children.”

A version of this article appeared on Medscape.com.

A phase 3 trial of a maternal vaccine candidate for respiratory syncytial virus (RSV) has been stopped early because the risk for preterm births is higher in the candidate vaccine group than in the placebo group.

By the time enrollment was stopped on February 25, 2022 because of the safety signal of preterm birth, 5328 pregnant women had been vaccinated, about half of the intended 10,000 enrollees. Of these, 3557 received the candidate vaccine RSV prefusion F protein–based maternal vaccine, and another 1771 received a placebo.

Data from the trial, sponsored by GSK, were immediately made available when recruitment and vaccination were stopped, and investigation of the preterm birth risk followed. Results of that analysis, led by Ilse Dieussaert, IR, vice president for vaccine development at GSK in Wavre, Belgium, are published online on March 13 in The New England Journal of Medicine. 

“We have discontinued our work on this RSV maternal candidate vaccine, and we are closing out all ongoing trials with the exception of the MAT-015 follow-on study to monitor subsequent pregnancies,” a GSK spokesperson said in an interview.

The trial was conducted in pregnant women aged 18-49 years to assess the efficacy and safety of the vaccine. The women were randomly assigned 2:1 to receive the candidate vaccine or placebo between 24 and 34 weeks’ gestation.
 

Preterm Births

The primary outcomes were any or severe medically assessed RSV-associated lower respiratory tract infection in infants from birth to 6 months and safety in infants from birth to 12 months.

According to the data, preterm birth occurred in 6.8% of the infants in the vaccine group and in 4.9% of those in the placebo group (relative risk [RR], 1.37; 95% CI, 1.08-1.74; P = .01). Neonatal death occurred in 0.4% in the vaccine group and 0.2% in the placebo group (RR, 2.16; 95% CI, 0.62-7.56; P = .23).

To date, only one RSV vaccine (Abrysvo, Pfizer) has been approved for use during pregnancy to protect infants from RSV-associated lower respiratory tract infection.

“It was a very big deal that this trial was stopped, and the new candidate won’t get approval.” said Aaron E. Glatt, MD, chair of the Department of Medicine and chief of Infectious Diseases and Hospital Epidemiologist at Mount Sinai South Nassau in Oceanside, New York.
 

Only One RSV Vaccine Approved in Pregnancy

Dr. Glatt pointed out the GSK vaccine is like the maternal vaccine that did get approved. “The data clearly show that there was a slight but increased risk in preterm labor,” Dr. Glatt said, “and while not as clearly shown, there was an increase in neonatal death in the group of very small numbers, but any neonatal death is of concern.”

The implications were disturbing, he added, “You’re giving this vaccine to prevent neonatal death.” Though the Pfizer vaccine that was granted approval had a very slight increase in premature birth, the risk wasn’t statistically significant, he pointed out, “and it showed similar benefits in preventing neonatal illness, which can be fatal.”

Dr. Glatt said that there is still a lingering concern with the approved vaccine, and he explained that most clinicians will give it closer to the end of the recommended time window of 34 weeks. “This way, even if there is a slight increase in premature term labor, you’re probably not going to have a serious outcome because the baby will be far enough along.”

A difference in the incidence of preterm birth between the experimental vaccine and placebo groups was predominantly found in low- and middle-income countries, according to Dieussaert’s team, “where approximately 50% of the trial population was enrolled and where the medical need for maternal RSV vaccines is the greatest.”

The RR was 1.56 (95% CI, 1.17-2.10) for low- and middle-income countries and 1.04 (95% CI, 0.68-1.58) for high-income countries. 

“If a smaller percentage of participants from low- and middle-income countries had been enrolled in our trial, the RR for preterm birth in the vaccine group as compared with the placebo group might have been reduced in the overall trial population,” they reported.

The authors explained that the data do not reveal the cause of the higher risk for preterm birth in the vaccine group.

“We do not know what caused the signal,” the company’s spokesperson added. “GSK completed all the necessary steps of product development including preclinical toxicology studies and clinical studies in nonpregnant women prior to starting the studies in pregnant women. There were no safety signals identified in any of the earlier parts of the clinical testing. There have been no safety signals identified in the other phase 3 trials for this vaccine candidate.”

Researchers did not find a correlation between preterm births in the treatment vs control groups with gestational age at the time of vaccination or with particular vaccine clinical trial material lots, race, ethnicity, maternal smoking, alcohol consumption, body mass index, or time between study vaccination and delivery, the GSK spokesperson said.

The spokesperson noted that the halted vaccine is different from GSK’s currently approved adjuvanted RSV vaccine (Arexvy) for adults aged 60 years or older.

What’s Next for Other Vaccines

Maternal vaccines have been effective in preventing other diseases in infants, such as tetanus, influenza, and pertussis, but RSV is a very hard virus to make a vaccine for, Dr. Glatt shared.

The need is great to have more than one option for a maternal RSV vaccine, he added, to address any potential supply concerns.

“People have to realize how serious RSV can be in infants,” he said. “It can be a fatal disease. This can be a serious illness even in healthy children.”

A version of this article appeared on Medscape.com.

A phase 3 trial of a maternal vaccine candidate for respiratory syncytial virus (RSV) has been stopped early because the risk for preterm births is higher in the candidate vaccine group than in the placebo group.

By the time enrollment was stopped on February 25, 2022 because of the safety signal of preterm birth, 5328 pregnant women had been vaccinated, about half of the intended 10,000 enrollees. Of these, 3557 received the candidate vaccine RSV prefusion F protein–based maternal vaccine, and another 1771 received a placebo.

Data from the trial, sponsored by GSK, were immediately made available when recruitment and vaccination were stopped, and investigation of the preterm birth risk followed. Results of that analysis, led by Ilse Dieussaert, IR, vice president for vaccine development at GSK in Wavre, Belgium, are published online on March 13 in The New England Journal of Medicine. 

“We have discontinued our work on this RSV maternal candidate vaccine, and we are closing out all ongoing trials with the exception of the MAT-015 follow-on study to monitor subsequent pregnancies,” a GSK spokesperson said in an interview.

The trial was conducted in pregnant women aged 18-49 years to assess the efficacy and safety of the vaccine. The women were randomly assigned 2:1 to receive the candidate vaccine or placebo between 24 and 34 weeks’ gestation.
 

Preterm Births

The primary outcomes were any or severe medically assessed RSV-associated lower respiratory tract infection in infants from birth to 6 months and safety in infants from birth to 12 months.

According to the data, preterm birth occurred in 6.8% of the infants in the vaccine group and in 4.9% of those in the placebo group (relative risk [RR], 1.37; 95% CI, 1.08-1.74; P = .01). Neonatal death occurred in 0.4% in the vaccine group and 0.2% in the placebo group (RR, 2.16; 95% CI, 0.62-7.56; P = .23).

To date, only one RSV vaccine (Abrysvo, Pfizer) has been approved for use during pregnancy to protect infants from RSV-associated lower respiratory tract infection.

“It was a very big deal that this trial was stopped, and the new candidate won’t get approval.” said Aaron E. Glatt, MD, chair of the Department of Medicine and chief of Infectious Diseases and Hospital Epidemiologist at Mount Sinai South Nassau in Oceanside, New York.
 

Only One RSV Vaccine Approved in Pregnancy

Dr. Glatt pointed out the GSK vaccine is like the maternal vaccine that did get approved. “The data clearly show that there was a slight but increased risk in preterm labor,” Dr. Glatt said, “and while not as clearly shown, there was an increase in neonatal death in the group of very small numbers, but any neonatal death is of concern.”

The implications were disturbing, he added, “You’re giving this vaccine to prevent neonatal death.” Though the Pfizer vaccine that was granted approval had a very slight increase in premature birth, the risk wasn’t statistically significant, he pointed out, “and it showed similar benefits in preventing neonatal illness, which can be fatal.”

Dr. Glatt said that there is still a lingering concern with the approved vaccine, and he explained that most clinicians will give it closer to the end of the recommended time window of 34 weeks. “This way, even if there is a slight increase in premature term labor, you’re probably not going to have a serious outcome because the baby will be far enough along.”

A difference in the incidence of preterm birth between the experimental vaccine and placebo groups was predominantly found in low- and middle-income countries, according to Dieussaert’s team, “where approximately 50% of the trial population was enrolled and where the medical need for maternal RSV vaccines is the greatest.”

The RR was 1.56 (95% CI, 1.17-2.10) for low- and middle-income countries and 1.04 (95% CI, 0.68-1.58) for high-income countries. 

“If a smaller percentage of participants from low- and middle-income countries had been enrolled in our trial, the RR for preterm birth in the vaccine group as compared with the placebo group might have been reduced in the overall trial population,” they reported.

The authors explained that the data do not reveal the cause of the higher risk for preterm birth in the vaccine group.

“We do not know what caused the signal,” the company’s spokesperson added. “GSK completed all the necessary steps of product development including preclinical toxicology studies and clinical studies in nonpregnant women prior to starting the studies in pregnant women. There were no safety signals identified in any of the earlier parts of the clinical testing. There have been no safety signals identified in the other phase 3 trials for this vaccine candidate.”

Researchers did not find a correlation between preterm births in the treatment vs control groups with gestational age at the time of vaccination or with particular vaccine clinical trial material lots, race, ethnicity, maternal smoking, alcohol consumption, body mass index, or time between study vaccination and delivery, the GSK spokesperson said.

The spokesperson noted that the halted vaccine is different from GSK’s currently approved adjuvanted RSV vaccine (Arexvy) for adults aged 60 years or older.

What’s Next for Other Vaccines

Maternal vaccines have been effective in preventing other diseases in infants, such as tetanus, influenza, and pertussis, but RSV is a very hard virus to make a vaccine for, Dr. Glatt shared.

The need is great to have more than one option for a maternal RSV vaccine, he added, to address any potential supply concerns.

“People have to realize how serious RSV can be in infants,” he said. “It can be a fatal disease. This can be a serious illness even in healthy children.”

A version of this article appeared on Medscape.com.

TOPLINE:

Taking a prescription opioid for pain management during pregnancy is associated with an increased risk for spontaneous preterm birth, data from a new case-control study of over 25,000 Medicaid patients showed.

METHODOLOGY:

• Researchers retrospectively reviewed data on pregnant patients enrolled in Tennessee Medicaid who experienced birth of a single baby at ≥ 24 weeks gestation (25,391 with opioid use disorder and 225,696 without).
• Median age of participants was 23 years; 58.1% were non-Hispanic White, 38.7% Black, 2.6% Hispanic, and 0.5% Asian.
• Controls were matched based on pregnancy start date, race, ethnicity, age at delivery (within 2 years), and history of prior preterm birth.
• Sensitivity analysis included the exclusion of opioid prescriptions dispensed within 3 days of the index date to account for potential opioid prescribing associated with labor pain.

TAKEAWAY:

• A total of 18,702 patients (7.4%) filled an opioid prescription during the 60 days prior to the index date.
• Each doubling of opioid morphine milligram equivalents (MMEs) prescribed during the 60 days was associated with a 4% increase in the odds of spontaneous preterm birth compared with no opioid exposure in the matched controls (adjusted odds ratio [aOR], 1.04; 95% CI, 1.01-1.08).
• Overall, 1573 pregnancies filled prescriptions for 900 MMEs or greater, which was associated with at least a 21% increased risk for spontaneous preterm birth compared with no opioid exposure (aOR, 1.21; 95% CI, 1.10-1.33).
• Researchers found no significant difference in odds of spontaneous preterm birth among included opioid types after adjusting for confounders and opioid MMD.

IN PRACTICE:

“This association may appear modest, especially considering that common, one-time prescriptions often fall in the 150-225 MME range, but these findings may provide more caution when prescribing multiple, higher strength opioids,” the authors wrote. “We also caution against the conclusion that lower doses, especially those below 100 MME, are safe; the confidence bands over the low dose range still include odds ratios that are consistent with meaningful harm.”

SOURCE:

Sarah S. Osmundson, MD, MS, of the Department of Obstetrics and Gynecology, Vanderbilt University Medical Center, Nashville, Tennessee, was the senior and corresponding author on the study. The study was published online on February 14 in JAMA Network Open.

LIMITATIONS:

Data are based on opioids prescribed and lack detail on actual use of opioids and nonprescription analgesics. Findings may not be generalizable to other populations or settings outside Medicaid.

DISCLOSURES:

No source of study funding listed. Dr. Osmundson reported receiving grant support from the National Institute on Drug Abuse during the conduct of the study. The other authors’ disclosures are listed on the original paper.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Taking a prescription opioid for pain management during pregnancy is associated with an increased risk for spontaneous preterm birth, data from a new case-control study of over 25,000 Medicaid patients showed.

METHODOLOGY:

• Researchers retrospectively reviewed data on pregnant patients enrolled in Tennessee Medicaid who experienced birth of a single baby at ≥ 24 weeks gestation (25,391 with opioid use disorder and 225,696 without).
• Median age of participants was 23 years; 58.1% were non-Hispanic White, 38.7% Black, 2.6% Hispanic, and 0.5% Asian.
• Controls were matched based on pregnancy start date, race, ethnicity, age at delivery (within 2 years), and history of prior preterm birth.
• Sensitivity analysis included the exclusion of opioid prescriptions dispensed within 3 days of the index date to account for potential opioid prescribing associated with labor pain.

TAKEAWAY:

• A total of 18,702 patients (7.4%) filled an opioid prescription during the 60 days prior to the index date.
• Each doubling of opioid morphine milligram equivalents (MMEs) prescribed during the 60 days was associated with a 4% increase in the odds of spontaneous preterm birth compared with no opioid exposure in the matched controls (adjusted odds ratio [aOR], 1.04; 95% CI, 1.01-1.08).
• Overall, 1573 pregnancies filled prescriptions for 900 MMEs or greater, which was associated with at least a 21% increased risk for spontaneous preterm birth compared with no opioid exposure (aOR, 1.21; 95% CI, 1.10-1.33).
• Researchers found no significant difference in odds of spontaneous preterm birth among included opioid types after adjusting for confounders and opioid MMD.

IN PRACTICE:

“This association may appear modest, especially considering that common, one-time prescriptions often fall in the 150-225 MME range, but these findings may provide more caution when prescribing multiple, higher strength opioids,” the authors wrote. “We also caution against the conclusion that lower doses, especially those below 100 MME, are safe; the confidence bands over the low dose range still include odds ratios that are consistent with meaningful harm.”

SOURCE:

Sarah S. Osmundson, MD, MS, of the Department of Obstetrics and Gynecology, Vanderbilt University Medical Center, Nashville, Tennessee, was the senior and corresponding author on the study. The study was published online on February 14 in JAMA Network Open.

LIMITATIONS:

Data are based on opioids prescribed and lack detail on actual use of opioids and nonprescription analgesics. Findings may not be generalizable to other populations or settings outside Medicaid.

DISCLOSURES:

No source of study funding listed. Dr. Osmundson reported receiving grant support from the National Institute on Drug Abuse during the conduct of the study. The other authors’ disclosures are listed on the original paper.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Taking a prescription opioid for pain management during pregnancy is associated with an increased risk for spontaneous preterm birth, data from a new case-control study of over 25,000 Medicaid patients showed.

METHODOLOGY:

• Researchers retrospectively reviewed data on pregnant patients enrolled in Tennessee Medicaid who experienced birth of a single baby at ≥ 24 weeks gestation (25,391 with opioid use disorder and 225,696 without).
• Median age of participants was 23 years; 58.1% were non-Hispanic White, 38.7% Black, 2.6% Hispanic, and 0.5% Asian.
• Controls were matched based on pregnancy start date, race, ethnicity, age at delivery (within 2 years), and history of prior preterm birth.
• Sensitivity analysis included the exclusion of opioid prescriptions dispensed within 3 days of the index date to account for potential opioid prescribing associated with labor pain.

TAKEAWAY:

• A total of 18,702 patients (7.4%) filled an opioid prescription during the 60 days prior to the index date.
• Each doubling of opioid morphine milligram equivalents (MMEs) prescribed during the 60 days was associated with a 4% increase in the odds of spontaneous preterm birth compared with no opioid exposure in the matched controls (adjusted odds ratio [aOR], 1.04; 95% CI, 1.01-1.08).
• Overall, 1573 pregnancies filled prescriptions for 900 MMEs or greater, which was associated with at least a 21% increased risk for spontaneous preterm birth compared with no opioid exposure (aOR, 1.21; 95% CI, 1.10-1.33).
• Researchers found no significant difference in odds of spontaneous preterm birth among included opioid types after adjusting for confounders and opioid MMD.

IN PRACTICE:

“This association may appear modest, especially considering that common, one-time prescriptions often fall in the 150-225 MME range, but these findings may provide more caution when prescribing multiple, higher strength opioids,” the authors wrote. “We also caution against the conclusion that lower doses, especially those below 100 MME, are safe; the confidence bands over the low dose range still include odds ratios that are consistent with meaningful harm.”

SOURCE:

Sarah S. Osmundson, MD, MS, of the Department of Obstetrics and Gynecology, Vanderbilt University Medical Center, Nashville, Tennessee, was the senior and corresponding author on the study. The study was published online on February 14 in JAMA Network Open.

LIMITATIONS:

Data are based on opioids prescribed and lack detail on actual use of opioids and nonprescription analgesics. Findings may not be generalizable to other populations or settings outside Medicaid.

DISCLOSURES:

No source of study funding listed. Dr. Osmundson reported receiving grant support from the National Institute on Drug Abuse during the conduct of the study. The other authors’ disclosures are listed on the original paper.
 

A version of this article appeared on Medscape.com.

NATIONAL HARBOR, MARYLAND — Women who experience an adverse pregnancy outcome during their first pregnancy are significantly more likely to experience either the same or any adverse pregnancy outcome in a subsequent pregnancy than are those with no adverse pregnancy outcome during a first pregnancy, based on data from more than 4000 individuals.

Adverse pregnancy outcomes (APOs) occur in approximately 20%-30% of pregnancies and contribute to significant perinatal morbidity, William A. Grobman, MD, of The Ohio State University, Columbus, said in a presentation at the Pregnancy Meeting sponsored by the Society for Maternal-Fetal Medicine (abstract 17).

Risk factors for APOs include nulliparity and prior APOs, as well as age, body mass index, and blood pressure, he said. However, less is known about factors identified early in a first pregnancy that might predict an APO in a second pregnancy, he explained.

Dr. Grobman and colleagues used data from the nuMoM2b Heart Health Study, a cohort of more than 10,000 nulliparous women at eight sites in the United States.

The current study included a subset of individuals with two pregnancies of at least 20 weeks’ gestation who were followed for up to 7 years after delivery via telephone and in-person visits and for whom APO information was available.

An APO was defined as any of a range of outcomes including hypertensive disorders of pregnancy, preterm birth at less than 37 weeks’ gestation, small-for-gestational age at birth (less than 5th percentile for weight), gestational diabetes, or fetal death.

The goal of the study was to determine patterns of APOs across two pregnancies, and to identify factors in the first pregnancy that might be associated with these patterns, Dr. Grobman said.

The study population included 4253 women from the nuMOM2b; of these, 1332 (31%) experienced an APO during their first pregnancies.

Women with an APO during the first pregnancy were significantly more likely to have a second APO than were those with no initial APO (40% vs. 15%), said Dr. Grobman. Overall, the APO that occurred most frequently in the first pregnancy was the one most likely to occur in the second.

However, “the increased risk for an APO during a second pregnancy was greater for any APO in women with a history of any APO compared to women with no prior APO,” he said.

In this study, the most common APOs were gestational diabetes and hypertensive disorders of pregnancy.

“In general, no risk markers were associated with a particular pattern of APO development,” Dr. Grobman said.

However, some markers from the first trimester of the first pregnancy were significantly associated with an APO in the second pregnancy, including body mass index, age older than 35 years, blood pressure, and cardiometabolic serum analytes. Also, the magnitude of APO recurrence risk was highest among non-Hispanic Black individuals compared with other ethnicities.

The findings were limited by a lack of data on placental pathology, Dr. Grobman noted during the discussion. However, the findings underscored the need to better understand the risk factors for APOs and develop prevention strategies, he said. The results also emphasize the need to account for transitions of care for patients who experience an APO, he added.
 

Data May Inform Patient Guidance

“Patients with an adverse pregnancy outcome in a first pregnancy often experience considerable anxiety when thinking about a second pregnancy,” Joseph R. Biggio Jr., MD, a maternal-fetal medicine specialist at Ochsner Health in New Orleans, said in an interview.

“This study helps to provide insight into factors which may be associated with increased risk in a subsequent pregnancy, and importantly identifies some factors that are potentially modifiable, such as BMI and blood pressure,” said Dr. Biggio, who served as a moderator for the session in which the study was presented.

“Based on the findings from this analysis, we need research to determine whether these findings apply to not only patients having their first pregnancy, but also adverse outcomes in any pregnancy,” Dr. Biggio said in an interview. “In addition, we need to explore whether modification of any of these risk factors can improve pregnancy outcomes, so that all patients can have the birth experience that they desire,” he said.

The study received no outside funding. Dr. Grobman and Dr. Biggio had no financial conflicts to disclose.

NATIONAL HARBOR, MARYLAND — Women who experience an adverse pregnancy outcome during their first pregnancy are significantly more likely to experience either the same or any adverse pregnancy outcome in a subsequent pregnancy than are those with no adverse pregnancy outcome during a first pregnancy, based on data from more than 4000 individuals.

Adverse pregnancy outcomes (APOs) occur in approximately 20%-30% of pregnancies and contribute to significant perinatal morbidity, William A. Grobman, MD, of The Ohio State University, Columbus, said in a presentation at the Pregnancy Meeting sponsored by the Society for Maternal-Fetal Medicine (abstract 17).

Risk factors for APOs include nulliparity and prior APOs, as well as age, body mass index, and blood pressure, he said. However, less is known about factors identified early in a first pregnancy that might predict an APO in a second pregnancy, he explained.

Dr. Grobman and colleagues used data from the nuMoM2b Heart Health Study, a cohort of more than 10,000 nulliparous women at eight sites in the United States.

The current study included a subset of individuals with two pregnancies of at least 20 weeks’ gestation who were followed for up to 7 years after delivery via telephone and in-person visits and for whom APO information was available.

An APO was defined as any of a range of outcomes including hypertensive disorders of pregnancy, preterm birth at less than 37 weeks’ gestation, small-for-gestational age at birth (less than 5th percentile for weight), gestational diabetes, or fetal death.

The goal of the study was to determine patterns of APOs across two pregnancies, and to identify factors in the first pregnancy that might be associated with these patterns, Dr. Grobman said.

The study population included 4253 women from the nuMOM2b; of these, 1332 (31%) experienced an APO during their first pregnancies.

Women with an APO during the first pregnancy were significantly more likely to have a second APO than were those with no initial APO (40% vs. 15%), said Dr. Grobman. Overall, the APO that occurred most frequently in the first pregnancy was the one most likely to occur in the second.

However, “the increased risk for an APO during a second pregnancy was greater for any APO in women with a history of any APO compared to women with no prior APO,” he said.

In this study, the most common APOs were gestational diabetes and hypertensive disorders of pregnancy.

“In general, no risk markers were associated with a particular pattern of APO development,” Dr. Grobman said.

However, some markers from the first trimester of the first pregnancy were significantly associated with an APO in the second pregnancy, including body mass index, age older than 35 years, blood pressure, and cardiometabolic serum analytes. Also, the magnitude of APO recurrence risk was highest among non-Hispanic Black individuals compared with other ethnicities.

The findings were limited by a lack of data on placental pathology, Dr. Grobman noted during the discussion. However, the findings underscored the need to better understand the risk factors for APOs and develop prevention strategies, he said. The results also emphasize the need to account for transitions of care for patients who experience an APO, he added.
 

Data May Inform Patient Guidance

“Patients with an adverse pregnancy outcome in a first pregnancy often experience considerable anxiety when thinking about a second pregnancy,” Joseph R. Biggio Jr., MD, a maternal-fetal medicine specialist at Ochsner Health in New Orleans, said in an interview.

“This study helps to provide insight into factors which may be associated with increased risk in a subsequent pregnancy, and importantly identifies some factors that are potentially modifiable, such as BMI and blood pressure,” said Dr. Biggio, who served as a moderator for the session in which the study was presented.

“Based on the findings from this analysis, we need research to determine whether these findings apply to not only patients having their first pregnancy, but also adverse outcomes in any pregnancy,” Dr. Biggio said in an interview. “In addition, we need to explore whether modification of any of these risk factors can improve pregnancy outcomes, so that all patients can have the birth experience that they desire,” he said.

The study received no outside funding. Dr. Grobman and Dr. Biggio had no financial conflicts to disclose.

NATIONAL HARBOR, MARYLAND — Women who experience an adverse pregnancy outcome during their first pregnancy are significantly more likely to experience either the same or any adverse pregnancy outcome in a subsequent pregnancy than are those with no adverse pregnancy outcome during a first pregnancy, based on data from more than 4000 individuals.

Adverse pregnancy outcomes (APOs) occur in approximately 20%-30% of pregnancies and contribute to significant perinatal morbidity, William A. Grobman, MD, of The Ohio State University, Columbus, said in a presentation at the Pregnancy Meeting sponsored by the Society for Maternal-Fetal Medicine (abstract 17).

Risk factors for APOs include nulliparity and prior APOs, as well as age, body mass index, and blood pressure, he said. However, less is known about factors identified early in a first pregnancy that might predict an APO in a second pregnancy, he explained.

Dr. Grobman and colleagues used data from the nuMoM2b Heart Health Study, a cohort of more than 10,000 nulliparous women at eight sites in the United States.

The current study included a subset of individuals with two pregnancies of at least 20 weeks’ gestation who were followed for up to 7 years after delivery via telephone and in-person visits and for whom APO information was available.

An APO was defined as any of a range of outcomes including hypertensive disorders of pregnancy, preterm birth at less than 37 weeks’ gestation, small-for-gestational age at birth (less than 5th percentile for weight), gestational diabetes, or fetal death.

The goal of the study was to determine patterns of APOs across two pregnancies, and to identify factors in the first pregnancy that might be associated with these patterns, Dr. Grobman said.

The study population included 4253 women from the nuMOM2b; of these, 1332 (31%) experienced an APO during their first pregnancies.

Women with an APO during the first pregnancy were significantly more likely to have a second APO than were those with no initial APO (40% vs. 15%), said Dr. Grobman. Overall, the APO that occurred most frequently in the first pregnancy was the one most likely to occur in the second.

However, “the increased risk for an APO during a second pregnancy was greater for any APO in women with a history of any APO compared to women with no prior APO,” he said.

In this study, the most common APOs were gestational diabetes and hypertensive disorders of pregnancy.

“In general, no risk markers were associated with a particular pattern of APO development,” Dr. Grobman said.

However, some markers from the first trimester of the first pregnancy were significantly associated with an APO in the second pregnancy, including body mass index, age older than 35 years, blood pressure, and cardiometabolic serum analytes. Also, the magnitude of APO recurrence risk was highest among non-Hispanic Black individuals compared with other ethnicities.

The findings were limited by a lack of data on placental pathology, Dr. Grobman noted during the discussion. However, the findings underscored the need to better understand the risk factors for APOs and develop prevention strategies, he said. The results also emphasize the need to account for transitions of care for patients who experience an APO, he added.
 

Data May Inform Patient Guidance

“Patients with an adverse pregnancy outcome in a first pregnancy often experience considerable anxiety when thinking about a second pregnancy,” Joseph R. Biggio Jr., MD, a maternal-fetal medicine specialist at Ochsner Health in New Orleans, said in an interview.

“This study helps to provide insight into factors which may be associated with increased risk in a subsequent pregnancy, and importantly identifies some factors that are potentially modifiable, such as BMI and blood pressure,” said Dr. Biggio, who served as a moderator for the session in which the study was presented.

“Based on the findings from this analysis, we need research to determine whether these findings apply to not only patients having their first pregnancy, but also adverse outcomes in any pregnancy,” Dr. Biggio said in an interview. “In addition, we need to explore whether modification of any of these risk factors can improve pregnancy outcomes, so that all patients can have the birth experience that they desire,” he said.

The study received no outside funding. Dr. Grobman and Dr. Biggio had no financial conflicts to disclose.

Buprenorphine use, compared with methadone use, in pregnancy has been linked with a slightly lower risk of major congenital malformations in a new study of medications for opioid use disorder (OUD).

Elizabeth A. Suarez, PhD, MPH, with the Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women’s Hospital and Harvard Medical School in Boston, and colleagues published the findings in JAMA Internal Medicine.

The lower risk for buprenorphine was small (risk ratio, 0.82; 95% confidence interval [CI], 0.69-0.97), and methadone use should not be ruled out on that basis, the authors wrote. For some women, particularly those on stable treatment before pregnancy or women who do not respond well to buprenorphine, methadone may be the better choice, they explained.
 

Either Medication Better Than Not Treating

The authors noted that either medication “is strongly recommended over untreated OUD during pregnancy.”

JAMA Internal Medicine Deputy Editor Deborah Grady, MD, MPH, with the Department of Medicine, University of California, San Francisco, emphasized that recommendation in an editor’s note, highlighting that treatment for OUD is critical to prevent infections, overdose, and death in pregnant women as well as neonatal opioid withdrawal syndrome and fetal death.

She stressed that internists and other primary care physicians have a key role in ensuring pregnant women with OUD receive appropriate treatment.

Given the importance of the issue, she wrote, “we have taken the unusual step of publishing two accompanying invited commentaries.”

Two developments may help increase use of buprenorphine, the study authors wrote. One is a recent study showing lower risk of adverse neonatal outcomes when buprenorphine is used during pregnancy compared with methadone. Another is the removal last year of the prescribing waiver for buprenorphine.
 

Study Included Medicaid Data Over 18 Years

The population-based cohort study used data from publicly insured Medicaid beneficiaries from 2000 to 2018. Pregnancies with enrollment from 90 days before pregnancy through 1 month after delivery and first-trimester use of buprenorphine or methadone were included (n = 13,360). The data were linked with infants’ health data.

The study group included 9,514 pregnancies with first-trimester buprenorphine exposure and 3,846 with methadone exposure. The risk of malformations overall was 50.9 (95% CI, 46.5-55.3) per 1000 pregnancies for buprenorphine and 60.6 (95% CI, 53.0-68.1) per 1000 pregnancies for methadone.

Major malformations were any cardiac malformations, ventricular septal defect, secundum atrial septal defect/nonprematurity-related patent foramen ovale, neural tube defects, oral clefts, and clubfoot.
 

Two Invited Commentaries Urge Caution in Interpretation

The two invited commentaries Dr. Grady mentioned in her editor’s note point both to the importance of the team’s findings and the need for better understanding of factors that may affect the choice of which OUD medication to use.

A commentary by Max Jordan Nguemeni Tiako, MD, MS, with the Department of Medicine, Brigham and Women’s Hospital, and colleagues, said that while the Suarez et al. data are important to share with patients, “the ultimate treatment decision must be the result of shared decision-making between a knowledgeable clinician and the patient, rather than promoting one medication over another.”

They urge putting the findings in context given the study population, which comprises a relatively stable group of women with OUD, most of whom were taking OUD medications before they got pregnant. The study sample excludes a substantial number of women who are chronically underinsured or uninsured, Dr. Tiako’s team wrote, because those included were enrolled in Medicaid for 3 consecutive months before pregnancy.

“We urge caution when extrapolating these findings to newly pregnant individuals with untreated OUD,” they wrote.
 

Both Medications are Safe

Cara Poland, MD, MEd, with the Henry Ford Health + Michigan State University Health Sciences in Grand Rapids, and coauthors, added in another commentary that Suarez et al. didn’t include a comparison between the population-level congenital defect rate and the defect rate for people using medications for OUD in pregnancy.

That comparison, they wrote, would have better illustrated the safety of medications for OUD “instead of simply comparing two medications with long-standing safety data.”

When a clinician starts a woman on medication for OUD in pregnancy, it’s important to understand several factors, including individual access to and comfort with different treatment approaches, they noted. It’s also important to weigh whether changing medications is worth the potential drawbacks of disrupting their well-managed care.

They wrote that the paper by Suarez et al. does not make the case for switching medications based on their findings.

Internists, they added, are ideal experts to explain risk of fetal abnormalities in the wider context of supporting engagement with continuous medication for OUD.

“In the absence of other concerns, switching medications (methadone to buprenorphine) or — worse — discontinuing [medication for] OUD because of this study runs counter to the substantial evidence regarding the safety of these medications during pregnancy,” Dr. Poland’s team wrote. “No treatment is without risk in pregnancy.”

This study was supported by the National Institute on Drug Abuse. In the Suarez et al. study, coauthors Dr. Hernández-Díaz, Dr. Gray, Dr. Connery, Dr. Zhu, and Dr. Huybrechts reported grants, personal fees and consulting payments from several pharmaceutical companies. Dr. Grady reports no relevant financial relationships in her editor’s note. No relevant financial relationships were reported by authors of the Tiako et al. commentary.

Regarding the commentary by Poland et al., grants were reported from the Michigan Health Endowment Fund, the Michigan Department of Health and Human Services, the National Institute on Drug Abuse and Blue Cross Blue Shield of Michigan outside the submitted work. No other disclosures were reported.

Buprenorphine use, compared with methadone use, in pregnancy has been linked with a slightly lower risk of major congenital malformations in a new study of medications for opioid use disorder (OUD).

Elizabeth A. Suarez, PhD, MPH, with the Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women’s Hospital and Harvard Medical School in Boston, and colleagues published the findings in JAMA Internal Medicine.

The lower risk for buprenorphine was small (risk ratio, 0.82; 95% confidence interval [CI], 0.69-0.97), and methadone use should not be ruled out on that basis, the authors wrote. For some women, particularly those on stable treatment before pregnancy or women who do not respond well to buprenorphine, methadone may be the better choice, they explained.
 

Either Medication Better Than Not Treating

The authors noted that either medication “is strongly recommended over untreated OUD during pregnancy.”

JAMA Internal Medicine Deputy Editor Deborah Grady, MD, MPH, with the Department of Medicine, University of California, San Francisco, emphasized that recommendation in an editor’s note, highlighting that treatment for OUD is critical to prevent infections, overdose, and death in pregnant women as well as neonatal opioid withdrawal syndrome and fetal death.

She stressed that internists and other primary care physicians have a key role in ensuring pregnant women with OUD receive appropriate treatment.

Given the importance of the issue, she wrote, “we have taken the unusual step of publishing two accompanying invited commentaries.”

Two developments may help increase use of buprenorphine, the study authors wrote. One is a recent study showing lower risk of adverse neonatal outcomes when buprenorphine is used during pregnancy compared with methadone. Another is the removal last year of the prescribing waiver for buprenorphine.
 

Study Included Medicaid Data Over 18 Years

The population-based cohort study used data from publicly insured Medicaid beneficiaries from 2000 to 2018. Pregnancies with enrollment from 90 days before pregnancy through 1 month after delivery and first-trimester use of buprenorphine or methadone were included (n = 13,360). The data were linked with infants’ health data.

The study group included 9,514 pregnancies with first-trimester buprenorphine exposure and 3,846 with methadone exposure. The risk of malformations overall was 50.9 (95% CI, 46.5-55.3) per 1000 pregnancies for buprenorphine and 60.6 (95% CI, 53.0-68.1) per 1000 pregnancies for methadone.

Major malformations were any cardiac malformations, ventricular septal defect, secundum atrial septal defect/nonprematurity-related patent foramen ovale, neural tube defects, oral clefts, and clubfoot.
 

Two Invited Commentaries Urge Caution in Interpretation

The two invited commentaries Dr. Grady mentioned in her editor’s note point both to the importance of the team’s findings and the need for better understanding of factors that may affect the choice of which OUD medication to use.

A commentary by Max Jordan Nguemeni Tiako, MD, MS, with the Department of Medicine, Brigham and Women’s Hospital, and colleagues, said that while the Suarez et al. data are important to share with patients, “the ultimate treatment decision must be the result of shared decision-making between a knowledgeable clinician and the patient, rather than promoting one medication over another.”

They urge putting the findings in context given the study population, which comprises a relatively stable group of women with OUD, most of whom were taking OUD medications before they got pregnant. The study sample excludes a substantial number of women who are chronically underinsured or uninsured, Dr. Tiako’s team wrote, because those included were enrolled in Medicaid for 3 consecutive months before pregnancy.

“We urge caution when extrapolating these findings to newly pregnant individuals with untreated OUD,” they wrote.
 

Both Medications are Safe

Cara Poland, MD, MEd, with the Henry Ford Health + Michigan State University Health Sciences in Grand Rapids, and coauthors, added in another commentary that Suarez et al. didn’t include a comparison between the population-level congenital defect rate and the defect rate for people using medications for OUD in pregnancy.

That comparison, they wrote, would have better illustrated the safety of medications for OUD “instead of simply comparing two medications with long-standing safety data.”

When a clinician starts a woman on medication for OUD in pregnancy, it’s important to understand several factors, including individual access to and comfort with different treatment approaches, they noted. It’s also important to weigh whether changing medications is worth the potential drawbacks of disrupting their well-managed care.

They wrote that the paper by Suarez et al. does not make the case for switching medications based on their findings.

Internists, they added, are ideal experts to explain risk of fetal abnormalities in the wider context of supporting engagement with continuous medication for OUD.

“In the absence of other concerns, switching medications (methadone to buprenorphine) or — worse — discontinuing [medication for] OUD because of this study runs counter to the substantial evidence regarding the safety of these medications during pregnancy,” Dr. Poland’s team wrote. “No treatment is without risk in pregnancy.”

This study was supported by the National Institute on Drug Abuse. In the Suarez et al. study, coauthors Dr. Hernández-Díaz, Dr. Gray, Dr. Connery, Dr. Zhu, and Dr. Huybrechts reported grants, personal fees and consulting payments from several pharmaceutical companies. Dr. Grady reports no relevant financial relationships in her editor’s note. No relevant financial relationships were reported by authors of the Tiako et al. commentary.

Regarding the commentary by Poland et al., grants were reported from the Michigan Health Endowment Fund, the Michigan Department of Health and Human Services, the National Institute on Drug Abuse and Blue Cross Blue Shield of Michigan outside the submitted work. No other disclosures were reported.

Buprenorphine use, compared with methadone use, in pregnancy has been linked with a slightly lower risk of major congenital malformations in a new study of medications for opioid use disorder (OUD).

Elizabeth A. Suarez, PhD, MPH, with the Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women’s Hospital and Harvard Medical School in Boston, and colleagues published the findings in JAMA Internal Medicine.

The lower risk for buprenorphine was small (risk ratio, 0.82; 95% confidence interval [CI], 0.69-0.97), and methadone use should not be ruled out on that basis, the authors wrote. For some women, particularly those on stable treatment before pregnancy or women who do not respond well to buprenorphine, methadone may be the better choice, they explained.
 

Either Medication Better Than Not Treating

The authors noted that either medication “is strongly recommended over untreated OUD during pregnancy.”

JAMA Internal Medicine Deputy Editor Deborah Grady, MD, MPH, with the Department of Medicine, University of California, San Francisco, emphasized that recommendation in an editor’s note, highlighting that treatment for OUD is critical to prevent infections, overdose, and death in pregnant women as well as neonatal opioid withdrawal syndrome and fetal death.

She stressed that internists and other primary care physicians have a key role in ensuring pregnant women with OUD receive appropriate treatment.

Given the importance of the issue, she wrote, “we have taken the unusual step of publishing two accompanying invited commentaries.”

Two developments may help increase use of buprenorphine, the study authors wrote. One is a recent study showing lower risk of adverse neonatal outcomes when buprenorphine is used during pregnancy compared with methadone. Another is the removal last year of the prescribing waiver for buprenorphine.
 

Study Included Medicaid Data Over 18 Years

The population-based cohort study used data from publicly insured Medicaid beneficiaries from 2000 to 2018. Pregnancies with enrollment from 90 days before pregnancy through 1 month after delivery and first-trimester use of buprenorphine or methadone were included (n = 13,360). The data were linked with infants’ health data.

The study group included 9,514 pregnancies with first-trimester buprenorphine exposure and 3,846 with methadone exposure. The risk of malformations overall was 50.9 (95% CI, 46.5-55.3) per 1000 pregnancies for buprenorphine and 60.6 (95% CI, 53.0-68.1) per 1000 pregnancies for methadone.

Major malformations were any cardiac malformations, ventricular septal defect, secundum atrial septal defect/nonprematurity-related patent foramen ovale, neural tube defects, oral clefts, and clubfoot.
 

Two Invited Commentaries Urge Caution in Interpretation

The two invited commentaries Dr. Grady mentioned in her editor’s note point both to the importance of the team’s findings and the need for better understanding of factors that may affect the choice of which OUD medication to use.

A commentary by Max Jordan Nguemeni Tiako, MD, MS, with the Department of Medicine, Brigham and Women’s Hospital, and colleagues, said that while the Suarez et al. data are important to share with patients, “the ultimate treatment decision must be the result of shared decision-making between a knowledgeable clinician and the patient, rather than promoting one medication over another.”

They urge putting the findings in context given the study population, which comprises a relatively stable group of women with OUD, most of whom were taking OUD medications before they got pregnant. The study sample excludes a substantial number of women who are chronically underinsured or uninsured, Dr. Tiako’s team wrote, because those included were enrolled in Medicaid for 3 consecutive months before pregnancy.

“We urge caution when extrapolating these findings to newly pregnant individuals with untreated OUD,” they wrote.
 

Both Medications are Safe

Cara Poland, MD, MEd, with the Henry Ford Health + Michigan State University Health Sciences in Grand Rapids, and coauthors, added in another commentary that Suarez et al. didn’t include a comparison between the population-level congenital defect rate and the defect rate for people using medications for OUD in pregnancy.

That comparison, they wrote, would have better illustrated the safety of medications for OUD “instead of simply comparing two medications with long-standing safety data.”

When a clinician starts a woman on medication for OUD in pregnancy, it’s important to understand several factors, including individual access to and comfort with different treatment approaches, they noted. It’s also important to weigh whether changing medications is worth the potential drawbacks of disrupting their well-managed care.

They wrote that the paper by Suarez et al. does not make the case for switching medications based on their findings.

Internists, they added, are ideal experts to explain risk of fetal abnormalities in the wider context of supporting engagement with continuous medication for OUD.

“In the absence of other concerns, switching medications (methadone to buprenorphine) or — worse — discontinuing [medication for] OUD because of this study runs counter to the substantial evidence regarding the safety of these medications during pregnancy,” Dr. Poland’s team wrote. “No treatment is without risk in pregnancy.”

This study was supported by the National Institute on Drug Abuse. In the Suarez et al. study, coauthors Dr. Hernández-Díaz, Dr. Gray, Dr. Connery, Dr. Zhu, and Dr. Huybrechts reported grants, personal fees and consulting payments from several pharmaceutical companies. Dr. Grady reports no relevant financial relationships in her editor’s note. No relevant financial relationships were reported by authors of the Tiako et al. commentary.

Regarding the commentary by Poland et al., grants were reported from the Michigan Health Endowment Fund, the Michigan Department of Health and Human Services, the National Institute on Drug Abuse and Blue Cross Blue Shield of Michigan outside the submitted work. No other disclosures were reported.