Maternal-Fetal Medicine Units Network Research Articles

Neurodevelopmental Outcomes After Late Preterm Antenatal Corticosteroids

The Antenatal Late Preterm Steroids (ALPS) trial changed clinical practice in the United States by finding that antenatal betamethasone at 34 to 36 weeks decreased short-term neonatal respiratory morbidity. However, the trial also found increased risk of neonatal hypoglycemia after betamethasone. This follow-up study focused on long-term neurodevelopmental outcomes after late preterm steroids. To evaluate whether administration of late preterm (34-36 completed weeks) corticosteroids affected childhood neurodevelopmental outcomes. Prospective follow-up study of children aged 6 years or older whose birthing parent had enrolled in the multicenter randomized clinical trial, conducted at 13 centers that participated in the Maternal-Fetal Medicine Units (MFMU) Network cycle from 2011-2016. Follow-up was from 2017-2022. Twelve milligrams of intramuscular betamethasone administered twice 24 hours apart. The primary outcome of this follow-up study was a General Conceptual Ability score less than 85 (-1 SD) on the Differential Ability Scales, 2nd Edition (DAS-II). Secondary outcomes included the Gross Motor Function Classification System level and Social Responsiveness Scale and Child Behavior Checklist scores. Multivariable analyses adjusted for prespecified variables known to be associated with the primary outcome. Sensitivity analyses used inverse probability weighting and also modeled the outcome for those lost to follow-up. Of 2831 children, 1026 enrolled and 949 (479 betamethasone, 470 placebo) completed the DAS-II at a median age of 7 years (IQR, 6.6-7.6 years). Maternal, neonatal, and childhood characteristics were similar between groups except that neonatal hypoglycemia was more common in the betamethasone group. There were no differences in the primary outcome, a general conceptual ability score less than 85, which occurred in 82 (17.1%) of the betamethasone vs 87 (18.5%) of the placebo group (adjusted relative risk, 0.94; 95% CI, 0.73-1.22). No differences in secondary outcomes were observed. Sensitivity analyses using inverse probability weighting or assigning outcomes to children lost to follow-up also found no differences between groups. In this follow-up study of a randomized clinical trial, administration of antenatal corticosteroids to persons at risk of late preterm delivery, originally shown to improve short-term neonatal respiratory outcomes but with an increased rate of hypoglycemia, was not associated with adverse childhood neurodevelopmental outcomes at age 6 years or older.

Venous Thromboembolism Risk Factors in Women With Obesity Who Undergo Cesarean Delivery.

Venous thromboembolism (VTE) is a leading cause of maternal mortality. Obesity and cesarean delivery are established risk factors for pregnancy-related VTE. We identified additional risk factors among patients with obesity who underwent a cesarean delivery to identify those who need VTE prophylaxis. We conducted a secondary analysis of data from the Maternal-Fetal Medicine Units Network (MFMU) Cesarean Registry Database using a case-control design. Cases were identified as women with obesity having a pre-pregnancy body mass index of >30 kg/m2, who underwent cesarean delivery and subsequently developed deep venous thrombosis (DVT) or pulmonary embolism (PE). These women were compared to a control group of women with obesity who underwent cesarean delivery but did not develop DVT or PE. Analysis of risk factors associated with VTE was performed using Chi-Square test and Fisher's exact test. We identified 43 VTE cases and 172 controls in the MFMU database. Increased risk of VTE was noted in women with endometritis (OR of 4.58 [95% CI: 1.86-11.2, P = .0004]), receiving a blood transfusion (OR 17.07 [95% CI: 4.46-65.3, P = .0001]), having a coagulopathy (OR 27.73 [95% CI: 3.24-237.25, P = .0003]), and urinary tract infection (OR 2.39 [95% CI: 1.08-5.28, P = .03]). Important risk factors for VTE in women with obesity who undergo cesarean delivery include endometritis, intra- or post-operative transfusion, coagulopathy, and urinary tract infection. The presence of one or more of these factors may help guide provider decision-making regarding whether to administer thromboprophylaxis.

Researching COVID to enhance recovery (RECOVER) pregnancy study: Rationale, objectives and design.

Pregnancy induces unique physiologic changes to the immune response and hormonal changes leading to plausible differences in the risk of developing post-acute sequelae of SARS-CoV-2 (PASC), or Long COVID. Exposure to SARS-CoV-2 during pregnancy may also have long-term ramifications for exposed offspring, and it is critical to evaluate the health outcomes of exposed children. The National Institutes of Health (NIH) Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC aims to evaluate the long-term sequelae of SARS-CoV-2 infection in various populations. RECOVER-Pregnancy was designed specifically to address long-term outcomes in maternal-child dyads. RECOVER-Pregnancy cohort is a combined prospective and retrospective cohort that proposes to enroll 2,300 individuals with a pregnancy during the COVID-19 pandemic and their offspring exposed and unexposed in utero, including single and multiple gestations. Enrollment will occur both in person at 27 sites through the Eunice Kennedy Shriver National Institutes of Health Maternal-Fetal Medicine Units Network and remotely through national recruitment by the study team at the University of California San Francisco (UCSF). Adults with and without SARS-CoV-2 infection during pregnancy are eligible for enrollment in the pregnancy cohort and will follow the protocol for RECOVER-Adult including validated screening tools, laboratory analyses and symptom questionnaires followed by more in-depth phenotyping of PASC on a subset of the overall cohort. Offspring exposed and unexposed in utero to SARS-CoV-2 maternal infection will undergo screening tests for neurodevelopment and other health outcomes at 12, 18, 24, 36 and 48 months of age. Blood specimens will be collected at 24 months of age for SARS-CoV-2 antibody testing, storage and anticipated later analyses proposed by RECOVER and other investigators. RECOVER-Pregnancy will address whether having SARS-CoV-2 during pregnancy modifies the risk factors, prevalence, and phenotype of PASC. The pregnancy cohort will also establish whether there are increased risks of adverse long-term outcomes among children exposed in utero. Clinical Trial Registration: http://www.clinicaltrials.gov. Unique identifier: NCT05172011.

Tranexamic Acid to Prevent Obstetrical Hemorrhage After Cesarean Delivery

ABSTRACT Previous research has presented convincing evidence that the administration of tranexamic acid (TXA) after cesarean delivery can reduce the incidence of postpartum hemorrhage (PPH) and the associated mortality and morbidity. Although there have been several significant studies on this topic, they are limited by small sample sizes, which make the studies difficult to generalize and limit their statistical power. This study aimed to address that gap and assess clinical outcomes related to the administration of TXA in a large sample. This was a multicenter, double-blind, randomized controlled trial including 31 hospitals participating in the Maternal-Fetal Medicine Units Network of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Eligibility criteria included scheduled or unscheduled cesarean delivery of a singleton or twin gestation. Exclusion criteria included maternal age younger than 18 years, blood transfusion before randomization, plan for transfusion after randomization, contraindications to TXA, patient decision not to use blood products, or administration of antifibrolytic agents or uterotonic agents other than oxytocin. The primary outcome was maternal death or blood transfusion before hospital discharge or 7 days after delivery, whichever came first. Secondary outcomes included intraoperative blood loss of more than 1 L and treatments or interventions in response to bleeding or related complications within 7 days of delivery, as well as infectious complications within 6 weeks of delivery. Final analyses included 11,000 patients, with 5529 in the TXA group and 5471 in the placebo group. Baseline characteristics were not significantly different between groups, and no center-dependent differences were observed. The primary outcome was observed in 3.6% of patients in the TXA group and 4.3% of patients in the placebo group (adjusted relative risk, 0.89; P = 0.19). Intraoperative blood loss of more than 1 L was recorded in 7.3% and 8.0% in the tranexamic and placebo groups, respectively (relative risk, 0.90; 95% CI, 0.79–1.05). Treatments and interventions in response to bleeding occurred in 16.1% of individuals in the TXA group and 18.0% of those in the placebo group (relative risk, 0.90; 95% CI, 0.82–0.97). Infectious complications were reported in 3.2% and 2.5% in the TXA and placebo groups, respectively (relative risk, 1.28; 95% CI, 1.02–1.61). Sensitivity analysis showed similar results to initial analysis, and no significant differences were seen between groups in major safety outcomes. This analysis indicates that the administration of TXA during cesarean delivery did not lower the risk of maternal death or blood transfusion. These results are in direct contradiction to previous research showing that TXA is effective at reducing these outcomes. This trial was stronger than any previous studies in sample size and careful randomization ensuring equal representation of scheduled and unscheduled cesarean deliveries, which makes the contradiction to previous research especially relevant. Some limitations of this trial included limitations in time of administration of TXA as well as dosage. Outcomes related to these 2 variables are still largely unknown. This trial also excluded patients at high risk of thromboembolic phenomena, and the effect of TXA in this population is still unknown. Further research should focus on more diverse populations, as well as understanding variations in outcomes with timing and dosage, which this study did not address.

Desirability of outcome ranking for obstetrical trials: illustration and application to the ARRIVE trial

In randomized trials, 1 primary outcome is typically chosen to evaluate the consequences of an intervention, whereas other important outcomes are relegated to secondary outcomes. This issue is amplified for many obstetrical trials in which an intervention may have consequences for both the pregnant person and the child. In contrast, desirability of outcome ranking, a paradigm shift for the design and analysis of clinical trials based on patient-centric evaluation, allows multiple outcomes-including from >1 individual-to be considered concurrently. This study aimed to describe desirability of outcome ranking methodology tailored to obstetrical trials and to apply the methodology to maternal-perinatal paired (dyadic) outcomes in which both individuals may be affected by an intervention but may experience discordant outcomes (eg, an obstetrical intervention may improve perinatal but worsen maternal outcomes). This secondary analysis applies the desirability of outcome ranking methodology to data from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network ARRIVE trial. The original analysis found no substantial difference in the primary (perinatal composite) outcome, but a decreased risk of the secondary outcome of cesarean delivery with elective induction at 39 weeks. In the present desirability-of-outcome-ranking analysis, dyadic outcomes ranging from spontaneous vaginal delivery without severe neonatal complication (most desirable) to cesarean delivery with perinatal death (least desirable) were classified into 8 categories ranked by overall desirability by experienced investigators. Distributions of the desirability of outcome ranking were compared by estimating the probability of having a more desirable dyadic outcome with elective induction at 39 weeks of gestation than with expectant management. To account for various perspectives on these outcomes, a complementary analysis, called the partial credit strategy, was used to grade outcomes on a 100-point scale and estimate the difference in overall treatment scores between groups using a t test. All 6096 participants from the trial were included. The probability of a better dyadic outcome for a randomly selected patient who was randomized to elective induction was 53% (95% confidence interval, 51-54), implying that elective induction led to a better overall outcome for the dyad when taking multiple outcomes into account concurrently. Furthermore, the desirability-of-outcome-ranking probability of averting cesarean delivery with elective induction was 52% (95% confidence interval, 51-53), which was not at the expense of an operative vaginal delivery or a poorer outcome for the perinate (ie, survival with a severe neonatal complication or perinatal death). Randomization to elective induction was also advantageous in most of the partial credit score scenarios. Desirability-of-outcome-ranking methodology is a useful tool for obstetrical trials because it provides a concurrent view of the effect of an intervention on multiple dyadic outcomes, potentially allowing for better translation of data for decision-making and person-centered care.

Perinatal Morbidity in Healthy Obese Pregnant Individuals Delivered by Elective Repeat Cesarean at Term.

This study aimed to compare the risks of adverse perinatal outcomes by body mass index (BMI) categories in healthy pregnant individuals delivered by term elective repeat cesarean (ERCD) to describe an optimal timing of delivery in otherwise healthy patients at the highest-risk BMI threshold. A secondary analysis of a prospective cohort of pregnant individuals undergoing ERCD at 19 centers in the Maternal-Fetal Medicine Units Network from 1999 to 2002. Nonanomalous singletons undergoing prelabor ERCD at term were included. The primary outcome was composite neonatal morbidity; secondary outcomes included composite maternal morbidity and individual components of the composites. Patients were stratified by BMI classes and to identify a BMI threshold for which morbidity was the highest. Outcomes were then examined by completed week's gestation, between BMI classes. Multivariable logistic regression was used to calculate adjusted odds ratios (aOR) and 95% confidence intervals (CI). A total of 12,755 patients were included in analysis. Patient's with BMI ≥ 40 had the highest rates of newborn sepsis, neonatal intensive care unit admissions, and wound complications. While a weight-related response was observed between BMI class and neonatal composite morbidity (p < 0.001), only those with BMI ≥ 40 had significantly higher odds of composite neonatal morbidity (aOR: 1.4, 95% CI: 1.0-1.8). In analyses of patients with BMI ≥ 40 (n = 1,848), there was no difference in the incidence of composite neonatal or maternal morbidity across weeks' gestation at delivery; however, as gestational age approached 39 to 40 weeks, rates of adverse neonatal outcomes decreased, only to increase again at 41 weeks' gestation. Of note, the odds of the primary neonatal composite were the highest at 38 weeks compared with 39 weeks (aOR: 1.5, 95% CI: 1.1-2.0). Neonatal morbidity is significantly higher in pregnant individuals with BMI ≥40 delivering by ERCD. Despite this increased perinatal morbidity, delivery prior to 39 and after 41 weeks in these patients is associated with increased neonatal risks. · Obese patients without additional comorbidities have higher rates of neonatal morbidity.. · Patients with BMI ≥ 40 carry the highest odds of poor perinatal outcomes.. · Earlier timing of delivery does not appear to reduce this risk..

Maternal and Neonatal Outcomes of Trial of Labor Compared With Elective Cesarean Delivery According to Predicted Likelihood of Vaginal Delivery

(Abstracted from J Matern Fetal Neonatal Med 2022;35(26):10487–10493 In 2007, the Maternal-Fetal Medicine Unit (MFMU) Network developed the vaginal birth after cesarean (VBAC) calculator to help optimize the likelihood of a successful vaginal delivery. One study found that the risk of maternal and neonatal morbidity is no greater than that of elective repeat cesarean delivery (CD)—specifically when the likelihood of successful VBAC is &gt;70%.

Assessing the predictive accuracy of the new vaginal birth after cesarean delivery calculator

The vaginal birth after cesarean delivery calculator by the Maternal-Fetal Medicine Units Network was created to help providers counsel patients on predicted success of trial of labor after cesarean delivery using individualized risk assessment. The inclusion of race and ethnicity as predictors of vaginal birth after cesarean delivery in the 2007 calculator was problematic and potentially exacerbated racial disparities in obstetrics. Thus, a modified calculator without race and ethnicity was published in June 2021. This study aimed to assess the accuracy of the 2007 and 2021 Maternal-Fetal Medicine Units vaginal birth after cesarean delivery calculators in predicting vaginal birth after cesarean delivery success among racial/ethnic minority patients receiving obstetrical care at a single urban tertiary medical center. All patients with 1 previous low transverse cesarean delivery who underwent a trial of labor at term with a vertex singleton gestation at an urban tertiary medical center from May 2015 to December 2018 were reviewed. Demographic and clinical data were collected retrospectively. Associations between maternal characteristics and success of vaginal birth after cesarean delivery were assessed using univariate and multivariable logistic regression. Predicted vaginal birth after cesarean delivery success rates using the Maternal-Fetal Medicine Units calculator were compared with actual outcomes (ie, successful trial of labor after cesarean delivery/vaginal birth after cesarean delivery vs repeated cesarean delivery) across each racial and ethnic group. A total of 910 patients met eligibility criteria and attempted trial of labor after cesarean delivery; 662 (73%) achieved vaginal birth after cesarean delivery. The rate of vaginal birth after cesarean delivery was highest among Asian women (81%) and lowest among Black women (61%). Univariate analyses demonstrated that success of vaginal birth after cesarean delivery was associated with maternal body mass index <30 kg/m2, history of vaginal delivery, and absence of indication of arrest of dilation or descent for previous cesarean delivery. Multivariate analyses evaluating predictors of vaginal birth after cesarean delivery reported in the 2021 calculator showed that maternal age, history of arrest disorder for previous cesarean delivery, and treated chronic hypertension were not significant in our patient population. Most patients who were of White, Asian, or "Other" race with a vaginal birth after cesarean delivery had a 2007 calculator-predicted probability of vaginal birth after cesarean delivery of >65%, whereas most Black and Hispanic patients with a vaginal birth after cesarean delivery were more likely to have a predicted probability of vaginal birth after cesarean delivery between 35% and 65% (P<.001). Most White, Asian, and Other-race patients with a repeated cesarean delivery had a 2007 calculator-predicted probability of vaginal birth after cesarean delivery of >65%, whereas most Black and Hispanic patients with a repeated cesarean delivery had a predicted probability of vaginal birth after cesarean delivery between 35% and 65%. Across all racial and ethnic groups, most patients with a vaginal birth after cesarean delivery had a 2021 calculator-predicted probability of vaginal birth after cesarean delivery of >65%. The inclusion of race/ethnicity in the 2007 Maternal-Fetal Medicine Units vaginal birth after cesarean delivery calculator underestimated predicted vaginal birth after cesarean delivery success rates among Black and Hispanic patients receiving obstetrical care at an urban tertiary medical center. Thus, we support the use of the 2021 vaginal birth after cesarean delivery calculator without race/ethnicity. Excluding race and ethnicity from vaginal birth after cesarean delivery counseling may be one way in whichproviders can ultimately contribute toward the reduction of racial and ethnic disparity in maternal morbidity in the United States. Further research is needed to understand the implications of treated chronic hypertension for the success of vaginal birth after cesarean delivery.

Editorial introductions.

Current Opinion in Obstetrics and Gynecology was launched in 1989. It is one of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The field of obstetrics and gynecology is divided into ten sections that are reviewed once a year. Each section is assigned one or more Section Editors. They are the leading authorities in their area, who identify the most important topics at that time. Here we are pleased to introduce the Journal's Section Editors for this issue. SECTION EDITORS Deirdre LyellDeirdre LyellDr Lyell is a Professor of Obstetrics and Gynecology in the Division of Maternal-Fetal Medicine at Stanford University, USA, where she serves as the Associate Division Director, Director of the Program in Placental Disorders, and Program Director of the Maternal-Fetal Medicine Fellowship. Dr Lyell is a member of the Child Health Research Institute at Stanford, the March of Dimes Prematurity Research Center at Stanford, and conducts research in clinical obstetrics. From 2013–2016 she served as an alternate P.I. to the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Maternal-Fetal Medicine Unit (MFMU) Network, USA. In 2010 she formed the Program in Placental Disorders at Stanford, a multidisciplinary patient care and research program for women with placenta accreta and cofounded a Placenta Accreta Special Interest Group that meets annually at the Society for Maternal-Fetal Medicine meeting. Dr Lyell earned a Bachelors of Arts and Sciences in History and Biology from Stanford University and a Medical Degree from the George Washington University School of Medicine, USA. She completed residency training in Obstetrics and Gynecology at Brigham and Women's and Massachusetts General Hospitals, USA, and fellowship in maternal-fetal medicine at Stanford University. She is certified by the American Board of Obstetrics and Gynecology in obstetrics and gynecology and maternal-fetal medicine. Mark BoddyMark BoddyDr Mark Boddy received his bachelor's degree from Georgia State University, USA. He received his medical degree from the Medical College of Georgia prior to completing a residency in obstetrics and gynecology at Atlanta Medical Center, USA. He subsequently completed a fellowship in maternal fetal medicine at The George Washington University School of Medicine, USA. He practiced for 17 years in a hospital-based setting while also serving as a Regional Perinatal Director for the State of Georgia. Currently, Dr Boddy is an Associate Clinical Professor at Stanford University School of Medicine, USA and the Medical Director of the Stanford Children's Healthcare Perinatal Diagnostic Center in Salinas, California, USA. His interests include prenatal diagnosis, improving quality of care and patient safety. Martha RodeMartha RodeDr Martha Rode received her bachelor's degree in biology at Harvard University, USA, before attending medical school at the University of California, Los Angeles, USA. She then completed residency and a maternal-fetal medicine fellowship at the University of Pennsylvania in Philadelphia, USA. She has since worked in both academic and hospital-based practices on both the East Coast and Northern California Bay Area in USA. She is currently a Clinical Associate Professor at Stanford Medical School, USA, serving as the Medical Director of the Perinatal Diagnostic Center in Santa Cruz. Her interests include perinatal diagnosis and high-risk obstetrics as well as community physician outreach and continued education. Jane ChuehJane ChuehDr Jane Chueh received her bachelor's degrees in biology and humanities at Stanford University, USA. She attended medical school at University of California San Diego, USA and completed her residency at University of Washington, USA and her fellowships in maternal fetal medicine and clinical genetics at University of California San Francisco, USA. She has worked in both academic and hospital-based practices in the Northern California Bay Area. Currently she is a Clinical Professor at Stanford Medical School, serving as the Director of Prenatal Diagnosis and Therapy at Stanford Children's Health. She enjoys practicing prenatal diagnosis and high-risk obstetrics, collaborating in research projects related to ultrasound and simulation teaching, and mentoring Stanford undergraduates and medical students. Amy VoedischAmy VoedischAmy J Voedisch, MD, MSc, NCMP is a Clinical Associate Professor in the Division of Family Planning, in the Department of Obstetrics and Gynecology at Stanford University, USA. Dr Voedisch attended the Mayo Medical School in Rochester, Minnesota, USA, and completed her OB-GYN residency at Kaiser Permanente Santa Clara, USA. She then went on to a fellowship in family planning at Stanford University, becoming an expert in reproductive health services, with a focus on increasing access to contraception in underserved international areas. She also earned her master's degree in clinical sciences research during her fellowship. Dr Voedisch is an expert in perimenopause and menopause and is a North American Menopause Society Certified Menopause Practitioner (NCMP).

Racial bias in cesarean decision-making

Category II fetal heart tracing noted during continuous external fetal monitoring is a frequent indication for cesarean delivery in the United States despite its somewhat subjective interpretation. Black patients have higher rates of cesarean delivery and higher rates for this indication. Racial bias in clinical decision-making has been demonstrated throughout medicine, including in obstetrics. We sought to examine if racial bias affects providers' decisions about cesarean delivery for an indication of category II fetal heart tracings. We constructed an online survey study consisting of 2 clinical scenarios of patients in labor with category II tracings. Patient race was randomized to Black and White; the vignettes were otherwise identical. Participants had the option to continue with labor or to proceed with a cesarean delivery at 3 decision points in each scenario. Participants reported their own demographics anonymously. This survey was distributed to obstetrical providers via email, listserv, and social media. Data were analyzed using chi-square tests at each decision point in the overall sample and in subgroup analyses by various participant demographics. A total of 726 participants contributed to the study. We did not find significant racial bias in cesarean delivery decision-making overall. However, in a scenario of a patient with a previous cesarean delivery, Fisher's exact tests showed that providers <40 years old (n=322; P=.01) and those with <10 years of experience (n=239; P=.050) opted for a cesarean delivery for Black patients more frequently than for White patients at the first decision point. As labor progressed in this scenario, the rates of cesarean delivery equalized across patient race. Younger providers and those with fewer years of clinical experience demonstrated racial bias in cesarean delivery decision-making at the first decision point early in labor. Providers did not show racial bias as labor progressed, nor in the scenario with a patient without a previous cesarean delivery. This bias may be the consequence of provider training with the Maternal-Fetal Medicine Unit Network Vaginal Birth After Cesarean Calculator, developed in 2007, and widely used to estimate the probability of successful vaginal birth after a cesarean delivery. This calculator used race as a predictive factor until it was removed in June 2021. Future studies should investigate if this bias persists following this change, while also focusing on interventions to address these findings.

Maternal and neonatal outcomes of trial of labor compared with elective cesarean delivery according to predicted likelihood of vaginal delivery

Objective The vaginal birth after cesarean (VBAC) calculator developed by the Maternal-Fetal Medicine Units Network (MFMU) helps to identify the likelihood of VBAC. We sought to compare adverse maternal and neonatal outcomes of trial of labor after cesarean (TOLAC) to those of elective cesarean delivery after stratifying by VBAC likelihood. Study design This was a retrospective cohort study of all women whose primary low transverse segment cesarean delivery and subsequent singleton term delivery with vertex presentation occurred at an academic center from January 2009 to June 2018. Only data from the second pregnancy were analyzed. The final analysis included 835 women. The MFMU VBAC calculator was used to assess the likelihood of VBAC. The two primary outcomes were composite adverse maternal (death or severe maternal complications) and neonatal outcomes (perinatal death or severe neonatal complications). The analyses were stratified based on the VBAC likelihood (less than 60% and 60–100%). Multivariable logistic regression was used to calculate adjusted odds ratio (OR) and 95% confidence interval (CI), controlling for predefined covariates. Results Among women with VBAC likelihood less than 60%, TOLAC compared with elective cesarean was associated with increased odds of the primary adverse maternal outcome (16.4% vs. 4.2%; adjusted OR 4.60 [95%CI 1.48–14.35]) and the primary adverse neonatal outcome (17.8% vs. 6.3%; adjusted OR 3.93 [95%CI 1.31–11.75]). Among women with VBAC likelihood of 60–100%, TOLAC compared with elective cesarean was associated with decreased odds of the primary adverse maternal outcome (6.4% vs. 11%; adjusted OR 0.47 [95%CI 0.25–0.89]) and similar odds of the primary adverse neonatal outcome (6.7% vs. 8.3%; adjusted OR 0.98 [95%CI 0.52–1.84]). Conclusions Among women with a history of a primary low transverse cesarean delivery, those who underwent TOLAC compared to those who had elective cesarean had increased odds of adverse maternal and neonatal outcomes when VBAC likelihood was less than 60%.

Associations of anaemia and race with peripartum transfusion in three United States datasets.

Transfusion complicates a significant proportion of births in the United States, and Black women have greater prevalence of transfusion at delivery than White women. Antepartum anaemia, a risk factor for peripartum transfusion, is more common among Black women than White women. We aimed to describe the racial distribution of antepartum anaemia in three national datasets and to evaluate the peripartum transfusion rate and characteristics of transfusion recipients, to investigate disparities in haemostatic outcomes. We performed a retrospective analysis of Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units Network Cesarean Registry (CR), NICHD Consortium on Safe Labor Registry (CSL), and a cohort of deliveries at Universal Health Services hospitals (UHS). Univariable associations and multivariable logistic regressions were calculated between race, anaemia and transfusion. Covariates included age, parity, smoking, body mass index, type of insurance, and delivery mode. We included n=56,964 deliveries from CR (28% Black), 87,465 from UHS (12% Black), and 140,324 from CSL (24% Black). Anaemia prevalence was 8% in CR, 7% in UHS, and 13% in CSL. Anaemia was more common among Black patients (ORs 2.52, 2.61, and 1.48 respectively) and was associated with transfusion in all databases (ORs 6.46 [95% CI 5.78-7.22]; 5.79 [4.74-7.27]; 1.27 [1.18-1.37] respectively). After adjusting for covariates, Black patients had greater odds of transfusion than non-Black patients in CR (aOR 1.32 [1.16-1.50]), but not in UHS or CSL (aORs 1.19 [0.89-1.59] and 0.40 [0.36-0.44] respectively). In our retrospective cohort study using three US registries, we emphasized the link between anaemia and transfusion. Although anaemia was more prevalent among Black patients, the race-transfusion relationship differed between databases, indicating other unexplored factors are involved.

Racial and Ethnic Disparities Among Women Undergoing a Trial of Labor After Cesarean Delivery: Performance of the VBAC Calculator with and without Patients' Race/Ethnicity.

The Maternal Fetal Medicine Units Network (MFMU) vaginal birth after cesarean (VBAC) calculator is a clinical tool designed to predict trial of labor after cesarean delivery (TOLAC) success. The calculator has come under scrutiny for its inclusion of race and ethnicity, which systematically predicts a lower likelihood of success for patients who identify as African American or Hispanic. We hypothesized that the calculator would predict VBAC more accurately without the use of race or ethnicity. A retrospective chart review including all patients undergoing TOLAC from 2016 to 2019 was conducted. A multivariate logistic regression was used to compare one model that utilizes the original variables in predicting VBAC (model 1) and another that uses the same variables except for race and ethnicity (model 2). In model 1, race and ethnicity were the only variables not associated with the probability of successful TOLAC (p = 0.065). The area under the curve (AUC) for models 1 and 2 were 0.77 and 0.78, respectively. There was not a statistically significant difference between the predictive abilities of the two models (p = 0.40). Rates of PPH (p = 0.001), abruption (p = 0.04), intra-amniotic infection (p < 0.0001), and other postpartum complications (p = 0.005) differed significantly by race and ethnicity. The use of race and ethnicity did not contribute to the accuracy of VBAC prediction. The use of race and ethnicity in this predictive model should be omitted to prevent inherent bias and discrimination. There were also significant racial and ethnic differences in overall postpartum complication rates.

Why Equitable Access to Vaginal Birth Requires Abolition of Race-Based Medicine.

In 2010, the National Institute of Child Health and Human Development Maternal-Fetal Medicine Units (MFMU) Network developed a decision aid, the Vaginal Birth After Cesarean (VBAC) calculator, to help clinicians discern how one variable (race) might influence patients' success in delivering a baby vaginally following a prior birth by cesarean. The higher rate of cesarean deliveries among Black and Hispanic women in the United States has long demonstrated racial inequities in obstetrical care, however. Although the MFMU's new VBAC calculator no longer includes race or ethnicity, in response to calls for abolition of race-based medicine, this article argues that VBAC calculator use has never been race neutral. In fact, VBAC calculator use in the United States is laced with racism, compromises patients' autonomy, and undermines informed consent.

Reducing Implicit Bias in Maternity Care: A Framework for Action

Reducing Implicit Bias in Maternity Care: A Framework for Action

Impact of Maternal-Fetal Medicine Unit Networks’ publications on ACOG guidelines

Maternal-Fetal Medicine Units (MFMU) Network was created in 1986 to conduct well-designed trials. We sought to evaluate the impact of the Network’s publications on recommendations by ACOG—in obstetric practice bulletins (PB) and committee opinions (CO)—and with evaluative bibliometrics.

A Possible Mechanism of Action of 17α-Hydroxyprogesterone Caproate: Enhanced IL-10 Production.

The rate of recurrent spontaneous preterm birth (PTB) was reduced by 33% in the Maternal-Fetal Medicine Unit (MFMU) Network trial of 17α-hydroxyprogesterone caproate (17-OHPC), but the mechanism of action, 17 years later, remains elusive. The robustness of the interleukin-10 (IL-10) response to lipopolysaccharide (LPS) stimulation of leukocytes in pregnant women with a prior PTB correlates with gestational age at delivery. This study sought to determine if there is a relationship between the concentration of 17-OHPC and response to LPS stimulation. We performed a secondary analysis of data from the Omega-3 MFMU trial which evaluated the effectiveness of omega-3 fatty acid supplementation in reducing recurrent PTB. We utilized previously characterized data from a subanalyses of the Omega-3 trial of IL-10 and tumor necrosis factor alpha (TNF-α) levels from peripheral blood mononuclear cells stimulated with LPS. Blood was obtained from enrolled women at 16 to 22 weeks' gestation (baseline) and 25 to 28 weeks' gestation (posttreatment). All women received 17-OHPC and plasma 17-OHPC concentrations were measured at 25 to 28 weeks' gestation. We analyzed these data to determine if there was a relationship between 17-OHPC concentration and cytokine production. We then performed an in vitro study to determine if 17-OHPC could directly alter cytokine production by THP-1-derived macrophages. In the clinical samples, we found that 17-OHPC plasma concentrations were correlated with the quantity of the LPS-stimulated production of IL-10. TNF-α production after LPS stimulation was unrelated to 17-OHPC concentration. In the in vitro study, we demonstrate a 17-OHPC concentration dependent increase in IL-10 production. In women receiving 17-OHPC for PTB prevention, we demonstrate a relationship between plasma 17-OHPC and LPS-stimulated IL-10 production by circulating leukocytes. We also demonstrate that, in vitro, 17-OHPC treatment affects IL-10 production by LPS-stimulated macrophages. Collectively, these findings support an immunomodulatory mechanism of action of 17-OHPC in the prevention of recurrent PTB. · 17-OHPC plasma concentrations and LPS-stimulated IL-10 levels correlate in clinical samples in women at risk for recurrent preterm birth.. · 17-OHPC can modulate the response of LPS-stimulated macrophages to increase IL-10 production.. · There was no relationship between TNF-α and plasma concentration of 17-OHPC in clinical samples or in vitro..

Prediction of vaginal birth after cesarean delivery in term gestations: a calculator without race and ethnicity

Investigators have attempted to derive tools that could provide clinicians with an easily obtainable estimate of the chance of vaginal birth after cesarean delivery for those who undertake trial of labor after cesarean delivery. One tool that has been validated externally was derived from data from the Maternal-Fetal Medicine Units Cesarean Registry. However, concern has been raised that this tool includes the socially constructed variables of race and ethnicity. This study aimed to develop an accurate tool to predict vaginal birth after cesarean delivery, using data easily obtainable early in pregnancy, without the inclusion of race and ethnicity. This was a secondary analysis of the Cesarean Registry of the Maternal-Fetal Medicine Units Network. The approach to the current analysis is similar to that of the analysis in which the previous vaginal birth after cesarean delivery prediction tool was derived. Specifically, individuals were included in this analysis if they were delivered on or after 37 0/7 weeks' gestation with a live singleton cephalic fetus at the time of labor and delivery admission, had a trial of labor after cesarean delivery, and had a history of 1 previous low-transverse cesarean delivery. Information was only considered for inclusion in the model if it was ascertainable at an initial prenatal visit. Model selection and internal validation were performed using a cross-validation procedure, with the dataset randomly and equally divided into a training set and a test set. The training set was used to identify factors associated with vaginal birth after cesarean delivery and build the logistic regression predictive model using stepwise backward elimination. A final model was generated that included all variables found to be significant (P<.05). The accuracy of the model to predict vaginal birth after cesarean delivery was assessed using the concordance index. The independent test set was used to estimate classification errors and validate the model that had been developed from the training set, and calibration was assessed. The final model was then applied to the overall analytical population. Of the 11,687 individuals who met the inclusion criteria for this secondary analysis, 8636 (74%) experienced vaginal birth after cesarean delivery. The backward elimination variable selection yielded a model from the training set that included maternal age, prepregnancy weight, height, indication for previous cesarean delivery, obstetrical history, and chronic hypertension. Vaginal birth after cesarean delivery was significantly more likely for women who were taller and had a previous vaginal birth, particularly if that vaginal birth had occurred after a previous cesarean delivery. Conversely, vaginal birth after cesarean delivery was significantly less likely for women whose age was older, whose weight was heavier, whose indication for previous cesarean delivery was arrest of dilation or descent, and who had a history of medication-treated chronic hypertension. The model had excellent calibration between predicted and empirical probabilities and, when applied to the overall analytical population, an area under the receiver operating characteristic curve of 0.75 (95% confidence interval, 0.74-0.77), which is similar to the area under the receiver operating characteristic curve of the previous model (0.75) that included race and ethnicity. We successfully derived an accurate model (available at https://mfmunetwork.bsc.gwu.edu/web/mfmunetwork/vaginal-birth-after-cesarean-calculator), which did not include race or ethnicity, for the estimation of the probability of vaginal birth after cesarean delivery.

Predicting obstetrical anal sphincter injuries in patients who undergo vaginal birth after cesarean delivery

Women with a history of previous cesarean delivery must weigh the numerous potential risks and benefits of elective repeat cesarean delivery or trial of labor after cesarean delivery. Notably, 1 important risk of vaginal delivery is obstetrical anal sphincter injuries. Furthermore, the rate of obstetrical anal sphincter injuries is high among women undergoing vaginal birth after cesarean delivery. However, the risk of obstetrical anal sphincter injuries is not routinely included in the trial of labor after cesarean delivery counseling, and there is no tool available to risk stratify obstetrical anal sphincter injuries among women undergoing vaginal birth after cesarean delivery. This study aimed to develop and validate a predictive model to estimate the risk of obstetrical anal sphincter injuries in the setting of vaginal birth after cesarean delivery population to improve antenatal counseling of patients regarding risks of trial of labor after cesarean delivery. This study was a secondary subgroup analysis of the Maternal-Fetal Medicine Units Network Trial of Labor After Cesarean Delivery prospective cohort (1999-2002). We identified women within the Maternal-Fetal Medicine Units Network cohort with 1 previous cesarean delivery followed by a term vaginal birth after cesarean delivery. This Maternal-Fetal Medicine Units Network Vaginal Birth After Cesarean Delivery cohort was stratified into 2 groups based on the presence of obstetrical anal sphincter injuries, and baseline characteristics were compared with bivariate analysis. Significant covariates in bivariate testing were included in a backward stepwise logistic regression model to identify independent risk factors for obstetrical anal sphincter injuries and generate a predictive model for obstetrical anal sphincter injuries in the setting of vaginal birth after cesarean delivery. Internal validation was performed using bootstrapped bias-corrected estimates of model concordance indices, Brier scores, Hosmer-Lemeshow chi-squared values, and calibration plots. External validation was performed using data from a single-site retrospective cohort of women with a singleton vaginal birth after cesarean delivery from January 2011 to December2016. In this study, 10,697 women in the Maternal-Fetal Medicine Units Network Trial of Labor After Cesarean Delivery cohort met the inclusion criteria, and 669 women (6.3%) experienced obstetrical anal sphincter injuries. In the model, factors independently associated with obstetrical anal sphincter injuries included use of forceps (adjusted odds ratio, 5.08; 95% confidence interval, 4.10-6.31) and vacuum assistance (adjusted odds ratio, 2.64; 95% confidence interval, 2.02-3.44), along with increasing maternal age (adjusted odds ratio, 1.05; 95% confidence interval, 1.04-1.07 per year), body mass index (adjusted odds ratio, 0.99; 95% confidence interval, 0.97-1.00 per unit kg/m2), previous vaginal delivery (adjusted odds ratio, 0.19; 95% confidence interval, 0.15-0.23), and tobacco use during pregnancy (adjusted odds ratio, 0.59; 95% confidence interval, 0.43-0.82). Internal validation demonstrated appropriate discrimination (concordance index, 0.790; 95% confidence interval, 0.771-0.808) and calibration (Brier score, 0.047). External validation used data from 1266 women who delivered at a tertiary healthcare system, with appropriate model discrimination (concordance index, 0.791; 95% confidence interval, 0.735-0.846) and calibration (Brier score, 0.046). The model can be accessed at oasisriskscore.xyz. Our model provided a robust, validated estimate of the probability of obstetrical anal sphincter injuries during vaginal birth after cesarean delivery using known antenatal risk factors and 1 modifiable intrapartum risk factor and can be used to counsel patients regarding risks of trial of labor after cesarean delivery compared with risks of elective repeat cesarean delivery.

775 Racial and ethnic disparities in rates and success of trial of labor after cesarean

The Maternal-Fetal Medicine Units Network vaginal birth after cesarean (VBAC) calculator is widely used to predict success of trial of labor after cesarean (TOLAC). Predictor variables include race and ethnicity, raising concerns that this calculator is widening disparities in cesarean section rates. Our aim was to assess racial and ethnic disparities in rates of TOLAC. This is a population-based retrospective cohort study using National Center for Health Statistics live birth data between 2014 and 2018. Women who delivered a cephalic, singleton gestation, ≥ 37 weeks with a history of one prior cesarean section were included. TOLAC rates were calculated by race/ethnicity and stratified by insurance status. The primary outcome was rate of TOLAC by race/ethnicity. The secondary outcome was rate of VBAC among groups. Multivariate logistic regression was performed to adjust for BMI, maternal age, prior vaginal delivery and insurance status. 1,481,898 women met inclusion criteria; 57.3% Non-Hispanic White (NHW), 16.0% Non-Hispanic Black (NHB), 26.6% Hispanic. TOLAC rates were highest in NHB women (26.5% versus NHW 22.5% and Hispanic 23.1%; p<.001). Medicaid patients had higher rates of TOLAC compared to privately insured patients 23.5% vs 21.7% (p<0.001). For NHW women with Medicaid, rate of TOLAC was 20.9% vs 22.1% for private insurance (p<0.001), compared to NHB women 27.9% vs 22.5% (p<0.001), and Hispanic women (23.5% vs 19.8%, p<0.001). After adjustment, odds of TOLAC were similar in NHB (OR 1.01 95% CI 0.99-1.03), but lower in Hispanic women (OR 0.87 95% CI 0.85 – 0.88) compared to NHW women. Successful VBAC was significantly lower among NHB (OR 0.54 95% CI 0.52 – 0.56) and Hispanic (OR 0.84 95% CI 0.81-0.88) women compared to NHW women. Despite similar TOLAC rates between NHB and NHW women, VBAC is significantly lower in NHB women. Hispanic women have lower TOLAC and VBAC rates than NHW women. Race/ethnicity and tools that include this predictor may influence management of TOLAC and contribute to the disparity in cesarean section rate.