Tranexamic Acid to Prevent Obstetrical Hemorrhage after Cesarean Delivery.

BACKGROUND: Prophylactic use of tranexamic acid at the time of cesarean delivery has been shown to decrease the calculated blood loss, but the effect on the need for blood transfusions is unclear. METHODS: We randomly assigned patients undergoing cesarean delivery at 31 U.S. hospitals to receive either tranexamic acid or placebo after umbilical-cord clamping. The primary outcome was a composite of maternal death or blood transfusion by hospital discharge or 7 days post partum, whichever came first. Key secondary outcomes were estimated intraoperative blood loss of more than 1 liter (prespecified as a major secondary outcome), interventions for bleeding and related complications, the preoperative-to-postoperative change in the hemoglobin level, and postpartum infectious complications. Adverse events were assessed. RESULTS: A total of 11,000 participants underwent randomization (5529 to the tranexamic acid group and 5471 to the placebo group); scheduled cesarean delivery accounted for 50.1% and 49.2% of the deliveries in the respective groups. A primary-outcome event occurred in 201 of 5525 participants (3.6%) in the tranexamic acid group and in 233 of 5470 (4.3%) in the placebo group (adjusted relative risk, 0.89; 95.26% confidence interval [CI], 0.74 to 1.07; P = 0.19). Estimated intraoperative blood loss of more than 1 liter occurred in 7.3% of the participants in the tranexamic acid group and in 8.0% of those in the placebo group (relative risk, 0.91; 95% CI, 0.79 to 1.05). Interventions for bleeding complications occurred in 16.1% of the participants in the tranexamic acid group and in 18.0% of those in the placebo group (relative risk, 0.90; 95% CI, 0.82 to 0.97); the change in the hemoglobin level was -1.8 g per deciliter and -1.9 g per deciliter, respectively (mean difference, -0.1 g per deciliter; 95% CI, -0.2 to -0.1); and postpartum infectious complications occurred in 3.2% and 2.5% of the participants, respectively (relative risk, 1.28; 95% CI, 1.02 to 1.61). The frequencies of thromboembolic events and other adverse events were similar in the two groups. CONCLUSIONS: Prophylactic use of tranexamic acid during cesarean delivery did not lead to a significantly lower risk of a composite outcome of maternal death or blood transfusion than placebo. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development; ClinicalTrials.gov number, NCT03364491.).

A Trial of Hyperimmune Globulin to Prevent Congenital Cytomegalovirus Infection.

BACKGROUND: Primary cytomegalovirus (CMV) infection during pregnancy carries a risk of congenital infection and possible severe sequelae. There is no established intervention for preventing congenital CMV infection. METHODS: In this multicenter, double-blind trial, pregnant women with primary CMV infection diagnosed before 24 weeks' gestation were randomly assigned to receive a monthly infusion of CMV hyperimmune globulin (at a dose of 100 mg per kilogram of body weight) or matching placebo until delivery. The primary outcome was a composite of congenital CMV infection or fetal or neonatal death if CMV testing of the fetus or neonate was not performed. RESULTS: From 2012 to 2018, a total of 206,082 pregnant women were screened for primary CMV infection before 23 weeks of gestation; of the 712 participants (0.35%) who tested positive, 399 (56%) underwent randomization. The trial was stopped early for futility. Data on the primary outcome were available for 394 participants; a primary outcome event occurred in the fetus or neonate of 46 of 203 women (22.7%) in the group that received hyperimmune globulin and of 37 of 191 women (19.4%) in the placebo group (relative risk, 1.17; 95% confidence interval [CI] 0.80 to 1.72; P = 0.42). Death occurred in 4.9% of fetuses or neonates in the hyperimmune globulin group and in 2.6% in the placebo group (relative risk, 1.88; 95% CI, 0.66 to 5.41), preterm birth occurred in 12.2% and 8.3%, respectively (relative risk, 1.47; 95% CI, 0.81 to 2.67), and birth weight below the 5th percentile occurred in 10.3% and 5.4% (relative risk, 1.92; 95% CI, 0.92 to 3.99). One participant in the hyperimmune globulin group had a severe allergic reaction to the first infusion. Participants who received hyperimmune globulin had a higher incidence of headaches and shaking chills while receiving infusions than participants who received placebo. CONCLUSIONS: Among pregnant women, administration of CMV hyperimmune globulin starting before 24 weeks' gestation did not result in a lower incidence of a composite of congenital CMV infection or perinatal death than placebo. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Center for Advancing Translational Sciences; ClinicalTrials.gov number, NCT01376778.).

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

BACKGROUND: 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. OBJECTIVE: 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). STUDY DESIGN: 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. RESULTS: 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. CONCLUSION: 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.

Neurodevelopmental Outcomes After Late Preterm Antenatal Corticosteroids: The ALPS Follow-Up Study.

Importance: 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. Objective: To evaluate whether administration of late preterm (34-36 completed weeks) corticosteroids affected childhood neurodevelopmental outcomes. Design, Setting, and Participants: 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. Exposure: Twelve milligrams of intramuscular betamethasone administered twice 24 hours apart. Main Outcome and Measures: 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. Results: 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. Conclusion and Relevance: 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.

Long-term neurodevelopmental follow-up of children exposed to pravastatin in utero.

BACKGROUND: Preeclampsia, especially before term, increases the risk of child neurodevelopmental adverse outcomes. Biological plausibility, preclinical studies, and pilot clinical trials conducted by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Obstetric-Fetal Pharmacology Research Centers Network support the safety and use of pravastatin to prevent preeclampsia. OBJECTIVE: This study aimed to determine the effect of antenatal pravastatin treatment in high-risk pregnant individuals on their child's health, growth, and neurodevelopment. STUDY DESIGN: This was an ancillary follow-up cohort study of children born to mothers who participated in the Obstetric-Fetal Pharmacology Research Centers Network pilot trials of pravastatin vs placebo in individuals at high risk of preeclampsia (ClinicalTrials.gov; identifier NCT01717586). After obtaining written informed consent (and assent as appropriate), the parent was instructed to complete the Child Behavior Checklist. To assess the child's motor, cognitive, and developmental outcomes, a certified and blinded study psychologist completed child motor, cognitive, emotional, and behavioral assessments using validated tools. Given the small number of individuals in the studies, the 10- and 20-mg pravastatin groups were combined into 1 group, and the results of the pravastatin group were compared with that of the placebo group. RESULTS: Of 40 children born to mothers in the original trial, 30 (15 exposed in utero to pravastatin and 15 to placebo) were enrolled in this follow-up study. The time of follow-up, which was 4.7 years (interquartile range, 2.5-6.9), was not different between children in the pravastatin group and children in the placebo group. There was no difference in the child's body mass index percentiles per sex and corrected age, the rates of extremes of body mass index percentiles, or the report of any other medical or developmental complications between the 2 groups. No child born in the pravastatin group had any limitation in motor assessment compared with 2 children (13.3%) who walked with difficulty and 4 children (26.7%) who had reduced manual abilities in the placebo group. Moreover, children born to mothers who received pravastatin had a higher general mean conceptual ability score (98.2±16.7 vs 89.7±11.0; P=.13) and a lower frequency (15.4% vs 35.7%; P=.38) of having a score of <85 (ie, 1 standard deviation lower than the mean) compared with those in the placebo group. Finally, there was no difference in the parents' report on the Child Behavior Checklist between the 2 groups. CONCLUSION: This study reported on the long-term neuromotor, cognitive, and behavioral outcomes among children exposed to pravastatin in utero during the second and third trimesters of pregnancy. Although the data were limited by the original trial's sample size, no identifiable long-term neurodevelopmental safety signal was evident with the use of pravastatin during pregnancy. This favorable neonatal risk-benefit analysis justifies continued research using pravastatin in clinical trials.

First- or second-trimester SARS-CoV-2 infection and subsequent pregnancy outcomes.

BACKGROUND: SARS-CoV-2 infection during pregnancy is associated with adverse pregnancy outcomes, including fetal death and preterm birth. It is not known whether that risk occurs only during the time of acute infection or whether the risk persists later in pregnancy. OBJECTIVE: This study aimed to evaluate whether the risk of SARS-CoV-2 infection during pregnancy persists after an acute maternal illness. STUDY DESIGN: A retrospective cohort study of pregnant patients with and without SARS-CoV-2 infection delivering at 17 hospitals in the United States between March 2020 and December 2020. Patients experiencing a SARS-CoV-2-positive test at or before 28 weeks of gestation with a subsequent delivery hospitalization were compared with those without a positive SAR-CoV-2 test at the same hospitals with randomly selected delivery days during the same period. Deliveries occurring at <20 weeks of gestation in both groups were excluded. The study outcomes included fetal or neonatal death, preterm birth at <37 weeks of gestation and <34 weeks of gestation, hypertensive disorders of pregnancy (HDP), any major congenital malformation, and size for gestational age of <5th or <10th percentiles at birth based on published standards. HDP that were collected included HDP and preeclampsia with severe features, both overall and with delivery at <37 weeks of gestation. RESULTS: Of 2326 patients who tested positive for SARS-CoV-2 during pregnancy and were at least 20 weeks of gestation at delivery from March 2020 to December 2020, 402 patients (delivering 414 fetuses or neonates) were SARS-CoV-2 positive before 28 weeks of gestation and before their admission for delivery; they were compared with 11,705 patients without a positive SARS-CoV-2 test. In adjusted analyses, those with SARS-CoV-2 before 28 weeks of gestation had a subsequent increased risk of fetal or neonatal death (2.9% vs 1.5%; adjusted relative risk, 1.97; 95% confidence interval, 1.01-3.85), preterm birth at <37 weeks of gestation (19.6% vs 13.8%; adjusted relative risk, 1.29; 95% confidence interval, 1.02-1.63), and HDP with delivery at <37 weeks of gestation (7.2% vs 4.1%; adjusted relative risk, 1.74; 95% confidence interval, 1.19-2.55). There was no difference in the rates of preterm birth at <34 weeks of gestation, any major congenital malformation, and size for gestational age of <5th or <10th percentiles. In addition, there was no significant difference in the rate of gestational hypertension overall or preeclampsia with severe features. CONCLUSION: There was a modest increase in the risk of adverse pregnancy outcomes after SARS-CoV-2 infection.

PROMPT: Prospective Meta-analysis for Pessary Trials Study Protocol.

OBJECTIVE: Preterm birth, defined as birth before 37 weeks of gestation, is a leading cause of perinatal and infant mortality throughout the world. Preterm birth is also associated with long-term neurological disabilities and other significant health issues in children. A short cervix in the second trimester has been noted to be one of the strongest predictors of subsequent spontaneous preterm birth in both singleton and multiple pregnancies. Some studies have shown that cervical support in the form of an Arabin pessary lowers the risk of preterm birth in women with a singleton gestation and short cervical length; however, other studies have conflicting results. Our objective was to form an international collaborative of planned or ongoing randomized trials of pessary in singleton and twin gestations with a short cervix. STUDY DESIGN: In November 2014, an international group of investigators, who had initiated or were planning randomized trials of pessary for pregnant people with a short cervix and singleton or twin gestation to prevent preterm birth, formed a collaboration to plan a prospective individual patient data (IPD) meta-analysis of randomized trials (PROspective Meta-analysis of Pessary Trials [PROMPT]). The PROMPT investigators agreed on meta-analysis IPD hypotheses for singletons and twins, eligibility criteria, and a set of core baseline and outcome measures. The primary outcome is a composite of fetal death or preterm delivery before 32 weeks' gestation. Secondary outcomes include maternal and neonatal morbidities. The PROMPT protocol may be viewed as a written agreement among the study investigators who make up the PROMPT consortium (PROSPERO ID# CRD42018067740). RESULTS: Results will be published in phases as the individual participating studies are concluded and published. Results of the first phase of singleton and twin pessary trials are expected to be available in late 2022. Updates are planned as participating trials are completed and published. KEY POINTS: · Short cervical length predicts preterm birth.. · Results of prior cervical pessary trials are mixed.. · Meta-analysis of pessary trials protocol..

Cervical Pessary for Prevention of Preterm Birth in Individuals With a Short Cervix: The TOPS Randomized Clinical Trial.

Importance: A short cervix as assessed by transvaginal ultrasound is an established risk factor for preterm birth. Study findings for a cervical pessary to prevent preterm delivery in singleton pregnancies with transvaginal ultrasound evidence of a short cervix have been conflicting. Objective: To determine if cervical pessary placement decreases the risk of preterm birth or fetal death prior to 37 weeks among individuals with a short cervix. Design, Setting, and Participants: We performed a multicenter, randomized, unmasked trial comparing a cervical pessary vs usual care from February 2017 through November 5, 2021, at 12 centers in the US. Study participants were nonlaboring individuals with a singleton pregnancy and a transvaginal ultrasound cervical length of 20 mm or less at gestations of 16 weeks 0 days through 23 weeks 6 days. Individuals with a prior spontaneous preterm birth were excluded. Interventions: Participants were randomized 1:1 to receive either a cervical pessary placed by a trained clinician (n = 280) or usual care (n = 264). Use of vaginal progesterone was at the discretion of treating clinicians. Main Outcome and Measures: The primary outcome was delivery or fetal death prior to 37 weeks. Results: A total of 544 participants (64%) of a planned sample size of 850 were enrolled in the study (mean age, 29.5 years [SD, 6 years]). Following the third interim analysis, study recruitment was stopped due to concern for fetal or neonatal/infant death as well as for futility. Baseline characteristics were balanced between participants randomized to pessary and those randomized to usual care; 98.9% received vaginal progesterone. In an as-randomized analysis, the primary outcome occurred in 127 participants (45.5%) randomized to pessary and 127 (45.6%) randomized to usual care (relative risk, 1.00; 95% CI, 0.83-1.20). Fetal or neonatal/infant death occurred in 13.3% of those randomized to receive a pessary and in 6.8% of those randomized to receive usual care (relative risk, 1.94; 95% CI, 1.13-3.32). Conclusions and Relevance: Cervical pessary in nonlaboring individuals with a singleton gestation and with a cervical length of 20 mm or less did not decrease the risk of preterm birth and was associated with a higher rate of fetal or neonatal/infant mortality. Trial Registration: ClinicalTrials.gov Identifier: NCT02901626.

Development of a Definition of Postacute Sequelae of SARS-CoV-2 Infection.

Importance: SARS-CoV-2 infection is associated with persistent, relapsing, or new symptoms or other health effects occurring after acute infection, termed postacute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID. Characterizing PASC requires analysis of prospectively and uniformly collected data from diverse uninfected and infected individuals. Objective: To develop a definition of PASC using self-reported symptoms and describe PASC frequencies across cohorts, vaccination status, and number of infections. Design, Setting, and Participants: Prospective observational cohort study of adults with and without SARS-CoV-2 infection at 85 enrolling sites (hospitals, health centers, community organizations) located in 33 states plus Washington, DC, and Puerto Rico. Participants who were enrolled in the RECOVER adult cohort before April 10, 2023, completed a symptom survey 6 months or more after acute symptom onset or test date. Selection included population-based, volunteer, and convenience sampling. Exposure: SARS-CoV-2 infection. Main Outcomes and Measures: PASC and 44 participant-reported symptoms (with severity thresholds). Results: A total of 9764 participants (89% SARS-CoV-2 infected; 71% female; 16% Hispanic/Latino; 15% non-Hispanic Black; median age, 47 years [IQR, 35-60]) met selection criteria. Adjusted odds ratios were 1.5 or greater (infected vs uninfected participants) for 37 symptoms. Symptoms contributing to PASC score included postexertional malaise, fatigue, brain fog, dizziness, gastrointestinal symptoms, palpitations, changes in sexual desire or capacity, loss of or change in smell or taste, thirst, chronic cough, chest pain, and abnormal movements. Among 2231 participants first infected on or after December 1, 2021, and enrolled within 30 days of infection, 224 (10% [95% CI, 8.8%-11%]) were PASC positive at 6 months. Conclusions and Relevance: A definition of PASC was developed based on symptoms in a prospective cohort study. As a first step to providing a framework for other investigations, iterative refinement that further incorporates other clinical features is needed to support actionable definitions of PASC.

Information is power: The experiences, attitudes and needs of individuals who chose to have prenatal genomic sequencing for fetal anomalies.

OBJECTIVE: This study sought to evaluate the experiences of individuals who chose to participate in a study and receive prenatal genomic sequencing (pGS) for fetuses with congenital structural anomalies. METHOD: Individuals who received research results of prenatal sequencing were invited to participate in semi-structured interviews about their experiences. A constructivist grounded theory approach was used to code and analyze interviews. RESULTS: Thirty-three participants from 27 pregnancies were interviewed. Participants were motivated to enroll in the study to find out more about their fetus' condition and prepare for the future. The waiting period was a time of significant anxiety for participants. Most participants felt relief and closure upon receiving results, regardless of the category of result, and had a clear understanding of the implications of the results. CONCLUSION: Participants' experiences with pGS were often intertwined with the experience of having a fetus with an abnormality. Participants were satisfied with the decision to participate in research and the support they received from the healthcare team, although waiting for results was associated with anxiety. The healthcare team plays an integral role in setting expectations and validating feelings of anxiety, fear and uncertainty.

Association of SARS-CoV-2 Infection With Serious Maternal Morbidity and Mortality From Obstetric Complications.

Importance: It remains unknown whether SARS-CoV-2 infection specifically increases the risk of serious obstetric morbidity. Objective: To evaluate the association of SARS-CoV-2 infection with serious maternal morbidity or mortality from common obstetric complications. Design, Setting, and Participants: Retrospective cohort study of 14 104 pregnant and postpartum patients delivered between March 1, 2020, and December 31, 2020 (with final follow-up to February 11, 2021), at 17 US hospitals participating in the Eunice Kennedy Shriver National Institute of Child Health and Human Development's Gestational Research Assessments of COVID-19 (GRAVID) Study. All patients with SARS-CoV-2 were included and compared with those without a positive SARS-CoV-2 test result who delivered on randomly selected dates over the same period. Exposures: SARS-CoV-2 infection was based on a positive nucleic acid or antigen test result. Secondary analyses further stratified those with SARS-CoV-2 infection by disease severity. Main Outcomes and Measures: The primary outcome was a composite of maternal death or serious morbidity related to hypertensive disorders of pregnancy, postpartum hemorrhage, or infection other than SARS-CoV-2. The main secondary outcome was cesarean birth. Results: Of the 14 104 included patients (mean age, 29.7 years), 2352 patients had SARS-CoV-2 infection and 11 752 did not have a positive SARS-CoV-2 test result. Compared with those without a positive SARS-CoV-2 test result, SARS-CoV-2 infection was significantly associated with the primary outcome (13.4% vs 9.2%; difference, 4.2% [95% CI, 2.8%-5.6%]; adjusted relative risk [aRR], 1.41 [95% CI, 1.23-1.61]). All 5 maternal deaths were in the SARS-CoV-2 group. SARS-CoV-2 infection was not significantly associated with cesarean birth (34.7% vs 32.4%; aRR, 1.05 [95% CI, 0.99-1.11]). Compared with those without a positive SARS-CoV-2 test result, moderate or higher COVID-19 severity (n = 586) was significantly associated with the primary outcome (26.1% vs 9.2%; difference, 16.9% [95% CI, 13.3%-20.4%]; aRR, 2.06 [95% CI, 1.73-2.46]) and the major secondary outcome of cesarean birth (45.4% vs 32.4%; difference, 12.8% [95% CI, 8.7%-16.8%]; aRR, 1.17 [95% CI, 1.07-1.28]), but mild or asymptomatic infection (n = 1766) was not significantly associated with the primary outcome (9.2% vs 9.2%; difference, 0% [95% CI, -1.4% to 1.4%]; aRR, 1.11 [95% CI, 0.94-1.32]) or cesarean birth (31.2% vs 32.4%; difference, -1.4% [95% CI, -3.6% to 0.8%]; aRR, 1.00 [95% CI, 0.93-1.07]). Conclusions and Relevance: Among pregnant and postpartum individuals at 17 US hospitals, SARS-CoV-2 infection was associated with an increased risk for a composite outcome of maternal mortality or serious morbidity from obstetric complications.

One-year postpartum anthropometric outcomes in mothers and children in the LIFE-Moms lifestyle intervention clinical trials.

BACKGROUND/OBJECTIVES: Excess gestational weight gain (GWG) is a risk factor for maternal postpartum weight retention and excessive neonatal adiposity, especially in women with overweight or obesity. Whether lifestyle interventions to reduce excess GWG also reduce 12-month maternal postpartum weight retention and infant weight-for-length z score is unknown. Randomized controlled trials from the LIFE-Moms consortium investigated lifestyle interventions that began in pregnancy and tested whether there was benefit through 12 months on maternal postpartum weight retention (i.e., the difference in weight from early pregnancy to 12 months) and infant-weight-for-length z scores. SUBJECTS/METHODS: In LIFE-Moms, women (N = 1150; 14.1 weeks gestation at enrollment) with overweight or obesity were randomized within each of seven trials to lifestyle intervention or standard care. Individual participant data were combined and analyzed using generalized linear mixed models with trial entered as a random effect. The 12-month assessment was completed by 83% (959/1150) of women and 84% (961/1150) of infants. RESULTS: Compared with standard care, lifestyle intervention reduced postpartum weight retention (2.2 ± 7.0 vs. 0.7 ± 6.2 kg, respectively; difference of -1.6 kg (95% CI -2.5, -0.7; p = 0.0003); the intervention effect was mediated by reduction in excess GWG, which explained 22% of the effect on postpartum weight retention. Lifestyle intervention also significantly increased the odds (OR = 1.68 (95% CI, 1.26, 2.24)) and percentage of mothers (48.2% vs. 36.2%) at or below baseline weight at 12 months postpartum (yes/no) compared with standard care. There was no statistically significant treatment group effect on infant anthropometric outcomes at 12 months. CONCLUSIONS: Compared with standard care, lifestyle interventions initiated in pregnancy and focused on healthy eating, increased physical activity, and other behavioral strategies resulted in significantly less weight retention but similar infant anthropometric outcomes at 12 months postpartum in a large, diverse US population of women with overweight and obesity.

Cell-Free Total and Fetal DNA in First Trimester Maternal Serum and Subsequent Development of Preeclampsia.

Objective The objective of this study was to assess the relationship between first trimester cell-free total and fetal DNA in maternal plasma and the subsequent development of preeclampsia. Study Design Nested case-control study of patients enrolled in the Combined Antioxidant and Preeclampsia Prediction Studies prediction study of 175 women who did and 175 women who did not develop preeclampsia. The predictive values of cell-free total and fetal DNA and the subsequent development of preeclampsia were measured using receiver operating characteristic curves. Results Cell-free total DNA was higher in African American (median; 25-75%; 6.15; 0.14-28.73; p = 0.02) and Hispanic (4.95; 0.20-26.82; p = 0.037) compared with white women (2.33; 0.03-13.10). Levels of cell-free total DNA were also associated with maternal body mass index (BMI) (p = 0.02). Cell-free total DNA levels were similar between women who later developed preeclampsia (3.52; 0.11-25.3) and controls (3.74; 0.12-21.14, p = 0.96). Conclusion There is no significant difference in levels of cell-free total DNA in the first trimester in women who subsequently develop preeclampsia. Levels of cell-free total DNA in the first trimester are increased in African American and Hispanic compared with white women, and levels increase with increasing BMI.

Is Mid-trimester Insulin Resistance Predictive of Subsequent Puerperal Infection? A Secondary Analysis of Randomized Trial Data.

Objective The objective of this study was to examine whether there is an association between insulin resistance and subsequent development of puerperal infection by measuring insulin resistance in the mid-trimester using the homeostasis model assessment (HOMA:IR). Methods Secondary analysis of low-risk nulliparas enrolled in a multicenter preeclampsia prevention trial. HOMA:IR was measured on fasting plasma glucose and insulin concentrations among low-risk nulliparas between 22 and 26 weeks' gestation. Median HOMA:IR was compared between women who did and did not develop puerperal infection using Wilcoxon rank sum test. Logistic regression was used to control for potential confounders. Results Of 1,180 women with fasting glucose and insulin available, 121 (10.3%) had a puerperal infection. Median HOMA:IR was higher among those with subsequent puerperal infection (4.3 [interquartile, IQR: 2.2-20.5] vs. 2.6 [IQR: 1.5-6.7], p < 0.0001). After controlling for potentially confounding variables HOMA:IR was only marginally associated with an increased risk of development of puerperal infection, adjusted odds ratio: 1.01 (95% confidence interval: 1.00-1.02; p = 0.04) per unit increase. Elevated HOMA:IR performed poorly as a predictor of puerperal infection, with a positive predictive value of 15% and a negative predictive value of 92%. Conclusion Though associated with an increased risk of puerperal infection, insulin resistance, measured by HOMA:IR, is not a clinically useful predictor of puerperal infection.

Adverse pregnancy outcomes among women with prior spontaneous or induced abortions.

OBJECTIVE: The aim of the article is to determine whether prior spontaneous abortion (SAB) or induced abortion (IAB), or the interpregnancy interval are associated with subsequent adverse pregnancy outcomes in nulliparous women. METHODS: We performed a secondary analysis of data collected from nulliparous women enrolled in a completed trial of vitamins C and E or placebo for preeclampsia prevention. Adjusted odds ratios (ORs) for maternal and fetal outcomes were determined for nulliparous women with prior SABs and IABs as compared with primigravid participants. RESULTS: Compared with primigravidas, women with one prior SAB were at increased risk for perinatal death (adj. OR, 1.5; 95% CI, 1.1-2.3) in subsequent pregnancies. Two or more SABs were associated with an increased risk for spontaneous preterm birth (PTB) (adj. OR, 2.6, 95% CI, 1.7-4.0), preterm premature rupture of membranes (PROM) (adj. OR, 2.9; 95% CI, 1.6-5.3), and perinatal death (adj. OR, 2.8; 95% CI, 1.5-5.3). Women with one previous IAB had higher rates of spontaneous PTB (adj. OR, 1.4; 95% CI, 1.0-1.9) and preterm PROM (OR, 2.0; 95% CI, 1.4-3.0). An interpregnancy interval less than 6 months after SAB was not associated with adverse outcomes. CONCLUSION: Nulliparous women with a history of SAB or IAB, especially multiple SABs, are at increased risk for adverse pregnancy outcomes.

Optimizing Opioid Prescription Quantity After Cesarean Delivery: A Randomized Controlled Trial.

OBJECTIVE: To test whether an individualized opioid-prescription protocol (IOPP) with a shared decision-making component can be used without compromising postcesarean pain management. METHODS: In this multicenter randomized controlled noninferiority trial, we compared IOPP with shared decision making with a fixed quantity of opioid tablets at hospital discharge. We recruited at 31 centers participating in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Study participants had uncomplicated cesarean births. Follow-up occurred through 12 weeks postdischarge. Individuals with complicated cesarean births or history of opioid use in the pregnancy were excluded. Participants were randomized 1:1 to IOPP with shared decision making or fixed quantity (20 tablets of 5 mg oxycodone). In the IOPP group, we calculated recommended tablet quantity based on opioid use in the 24 hours before discharge. After an educational module and shared decision making, participants selected a quantity of discharge tablets (up to 20). The primary outcome was moderate to severe pain (score 4 or higher [possible range 0-10]) on the BPI (Brief Pain Inventory) at 1 week after discharge. A total sample size of 5,500 participants was planned to assess whether IOPP with shared decision making was not inferior to the fixed quantity of 20 tablets. RESULTS: From September 2020 to March 2022, 18,990 individuals were screened and 5,521 were enrolled (n=2,748 IOPP group, n=2,773 fixed-quantity group). For the primary outcome, IOPP with shared decision making was not inferior to fixed quantity (59.5% vs 60.1%, risk difference 0.67%; 95% CI, -2.03% to 3.37%, noninferiority margin -5.0) and resulted in significantly fewer tablets received (median 14 [interquartile range 4-20] vs 20, P <.001) through 90 days postpartum. CONCLUSION: Compared with fixed quantity, IOPP with shared decision making was noninferior for outpatient postcesarean analgesia at 1 week postdischarge and resulted in fewer prescribed opioid tablets at discharge. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT04296396.