Search

Objective To determine whether β2-adrenoceptor ( β2 AR) genotype is associated with shortening of the cervix or with preterm birth ( PTB) risk among women with a short cervix in the second trimester. Design A case-control ancillary study to a multicentre randomised controlled trial. Setting Fourteen participating centres of the Maternal-Fetal Medicine Units Network of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Population Four hundred thirty-nine women, including 315 with short cervix and 124 with normal cervical length. Methods Nulliparous women with cervical length <30 mm upon a 16-22-week transvaginal sonogram and controls frequency-matched for race/ethnicity with cervical lengths ≥40 mm were studied. β2 AR genotype was determined at positions encoding for amino acid residues 16 and 27. Main outcome measures Genotype distributions were compared between case and control groups. Within the short cervix group, pregnancy outcomes were compared by genotype, with a primary outcome of PTB <37 weeks. Results Genotype data were available at position 16 for 433 women and at position 27 for 437. Using a recessive model testing for association between short cervix and genotype, and adjusted for ethnicity, there was no statistical difference between cases and controls for Arg16 homozygosity ( OR 0.7, 95% CI 0.4-1.3) or Gln27 homozygosity ( OR 0.9, 95% CI 0.3-2.7). Among cases, Arg16 homozygosity was not associated with protection from PTB or spontaneous PTB. Gln27 homozygosity was not associated with PTB risk, although sample size was limited. Conclusions β2 AR genotype does not seem to be associated with short cervical length or with PTB following the second-trimester identification of a short cervix. Influences on PTB associated with β2 AR genotype do not appear to involve a short cervix pathway. [ABSTRACT FROM AUTHOR]

The author discusses the study conducted by M. Ramphul and his team on the assessment of instrument placement on adverse maternal and neonatal care. The author mentions that the study was shown as suboptimal in three of ten operative vaginal deliveries. He states the importance of implementing education and training in lowering the rate of suboptimal instrument placement.

Objective:  This study aimed to develop a prediction model that estimates the probability that a pregnant person who has had asymptomatic or mild coronavirus disease 2019 (COVID-19) prior to delivery admission will progress in severity to moderate, severe, or critical COVID-19., Study Design:  This was a secondary analysis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive patients who delivered from March through December 2020 at hospitals across the United States. Those eligible for this analysis presented for delivery with a current or previous asymptomatic or mild SARS-CoV-2 infection. The primary outcome was moderate, severe, or critical COVID-19 during the delivery admission through 42 days postpartum. The prediction model was developed and internally validated using stratified cross-validation with stepwise backward elimination, incorporating only variables that were known on the day of hospital admission., Results:  Of the 2,818 patients included, 26 (0.9%; 95% confidence interval [CI], 0.6-1.3%) developed moderate-severe-critical COVID-19 during the study period. Variables in the prediction model were gestational age at delivery admission (adjusted odds ratio [aOR], 1.15; 95% CI, 1.08-1.22 per 1-week decrease), a hypertensive disorder in a prior pregnancy (aOR 3.05; 95% CI, 1.25-7.46), and systolic blood pressure at admission (aOR, 1.04; 95% CI, 1.02-1.05 per mm Hg increase). This model yielded an area under the receiver operating characteristic curve of 0.82 (95% CI, 0.72-0.91)., Conclusion:  Among individuals presenting for delivery who had asymptomatic-mild COVID-19, gestational age at delivery admission, a hypertensive disorder in a prior pregnancy, and systolic blood pressure at admission were predictive of delivering with moderate, severe, or critical COVID-19. This prediction model may be a useful tool to optimize resources for SARS-CoV-2-infected pregnant individuals admitted for delivery., Key Points: · Three factors were associated with delivery with more severe COVID-19.. · The developed model yielded an area under the receiver operating characteristic curve of 0.82 and model fit was good.. · The model may be useful tool for SARS-CoV-2 infected pregnancies admitted for delivery.., Competing Interests: None declared., (Thieme. All rights reserved.)

The management of hypertensive disease in pregnancy is currently guided by practice recommendations based largely on observational data from a half century ago and has changed only superficially since that time. These recommendations are both narrowly prescriptive (women without traditional features of severe disease should all be delivered at exactly 37 weeks and 0 days,) and at the same time frustratingly ambiguous (the presence of epigastric pain unresponsive to repeat analgesics precludes expectant management at any gestational age, regardless of laboratory studies.) Guidelines which ignore recent data from the obstetric, pediatric and internal medicine literature too often lead practitioners to be more aggressive than necessary in the delivery of very premature pregnancies, and, conversely, more complacent than patient safety would support in prolonging pregnancy with advanced fetal maturity. We present here an alternative, organ-specific based approach to the management of gestational hypertension which allows and encourages practitioners to formulate a management plan based on a thoughtful and, when possible, evidence- based synthesis of the continuous variables of blood pressure, degree of organ dysfunction and response to treatment, gestational age, and patient balancing of maternal and fetal/neonatal risks. Such clinical care is more complex and nuanced than simply basing life-altering critical management decisions, including timing of delivery, on whether the patient does, or does not have any one of the conditions described by box 4 of the current American College of Obstetricians and Gynecologists practice guidelines. Nonetheless, we believe this approach will not only improve care but will also open the door to useful investigations into prevention and management of the various entities traditionally considered as the same disease process., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Background: Perinatal depression has been suggested to adversely impact child neurodevelopment. However, the complexity of the early childhood environment challenges conclusive findings., Objective: To evaluate whether there is an association between perinatal depressive symptoms and child intelligence quotient (IQ) at 5 years of age., Study Design: Secondary analysis of an ancillary study to a multicenter randomized trial of thyroxine therapy for pregnant individuals with subclinical hypothyroidism. Dyads of infants and birthing parent, with completed Center for Epidemiological Studies-Depression (CES-D) screens during pregnancy and postpartum and child neurodevelopment testing completed at five years of age (n=209) were included. CES-D screening was performed at 11-20 weeks, 34-38 weeks, and one-year postpartum. Depressive symptoms were categorized as antenatal (i.e., a positive screen at any point during pregnancy) or postpartum. The primary outcome was child IQ score < 85 at 5 years of age using the Wechsler Preschool and Primary Scale of Intelligence III (WPPSI-III) Full Scale test. Secondary outcomes included other assessments of childhood neurodevelopment. Bivariable analyses and multivariable logistic regressions were utilized., Results: Of the 209 birthing people included, 72 (34%) screened positive for depression during pregnancy and 32 (15%) screened positive one year postpartum. Children born to individuals with a positive antenatal depression screen had a higher odds of IQ < 85 at 5 years of age compared with children born to individuals with a CES-D < 16 (35% vs. 18%, OR 2.4, 95% CI 1.2-4.7). Similar findings were seen for children born to individuals with a positive postpartum depression screen (47% vs. 21%, OR 3.3, 95% CI 1.5-7.3). These associations did not persist in multivariable analyses that controlled for social determinants of health and clinical characteristics (adjusted odd ratio [aOR] 1.4, 95% CI 0.7-3.1; aOR 2.1, 95% CI 0.9-5.1, for antenatal and postpartum depressive symptoms, respectively). Similar findings were observed for other adverse neurodevelopmental outcomes., Conclusions: Having a positive perinatal depression screen was not associated with child cognitive outcomes after controlling for covariates including social determinants of health., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Following the results of the A Randomized Trial of Induction Versus Expectant Management trial, which demonstrated a reduction in cesarean delivery with no increase in adverse perinatal outcomes after elective induction of labor in low-risk nulliparous patients at 39 weeks of gestation compared with expectant management, the use of induction of labor has increased. Current evidence is insufficient to recommend mid- to high-dose regimens over low-dose regimens for routine induction of labor., Objective: This study aimed to evaluate the association between oxytocin regimen and cesarean delivery and an adverse perinatal composite outcome in low-risk nulliparous patients undergoing induction of labor at ≥39 weeks of gestation., Study Design: This was a secondary analysis of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network's A Randomized Trial of Induction Versus Expectant Management randomized trial. Patients who received a mid- to high-dose oxytocin regimen (starting or incremental increase >2 mU/min) were compared with those who received a low-dose oxytocin regimen (starting and incremental increase ≤2 mU/min). The co-primary outcomes for this secondary analysis were (1) cesarean delivery and (2) composite of perinatal death or severe neonatal complications. Multivariate Poisson regression was used to estimate adjusted relative risks and 97.5% confidence intervals for the co-primary endpoints and 95% confidence intervals for binomial outcomes, and multinomial logistic regression was used to estimate adjusted odds ratios and 95% adjusted relative risks for multinomial outcomes., Results: Of 6106 participants enrolled in the primary trial, 2933 underwent induction of labor with oxytocin: 861 in the mid- to high-dose group and 2072 in the low-dose group. The lower frequency of cesarean delivery in the mid- to high-dose group than in the low-dose group (20.3% vs 25.2%, respectively; relative risk, 0.81; 95% confidence interval, 0.69-0.94) was not significant after adjustment (adjusted relative risk, 0.90; 97.5% confidence interval, 0.76-1.07). The composite of perinatal death or severe neonatal complications was more frequent in the mid- to high-dose group than in the low-dose group (6.7% vs 4.3%, respectively; relative risk, 1.55; 95% confidence interval, 1.13-2.14) and remained significant after adjustment (adjusted relative risk, 1.61; 97.5% confidence interval, 1.11-2.35). Most cases in the composite were from the respiratory support (5.2% in the mid- to high-dose group vs 3.1% in the low-dose group) component, with an increase in transient tachypnea in newborns (3.8% in the mid- to high-dose group vs 2.5% in the low-dose group; adjusted relative risk, 1.63; 95% confidence interval, 1.04-2.54). The duration of neonatal respiratory support for 1 day was significantly longer in the mid- to high-dose group than in the low-dose group (3.5% vs 1.4%, respectively; adjusted relative risk, 2.59; 95% confidence interval, 1.52-4.39). However, support beyond 1 day was not different between the 2 groups. Compared with the low-dose group, the mid- to high-dose group had a higher operative vaginal delivery rate (10.0% vs 7.0%, respectively; adjusted relative risk, 1.54; 95% confidence interval, 1.18-2.00) and shorter duration of time from start of oxytocin to delivery (crude median: 12 hours [interquartile range, 8-17] vs 13 hours [interquartile range 9-19], respectively; adjusted median difference: -2 [95% CI, -2 to -1]; P<.001)., Conclusion: The use of mid-to high-dose oxytocin regimens for induction of labor in nulliparas at ≥39 weeks of gestation was not associated with a lower cesarean delivery rate or improved neonatal outcomes compared with the use of low-dose oxytocin regimens. Although the use of mid- to high-dose oxytocin regimens was associated with a shorter duration of labor, there was an increase in self-limited neonatal respiratory support and no difference in cesarean delivery rates. More evidences are needed to define the magnitude of potential maternal and neonatal benefits and risks associated with oxytocin regimens., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: To examine the incidence of overt hypothyroidism 1 and 5 years after pregnancies where screening before 21 weeks identified subclinical hypothyroidism (SH) or hypothyroxinemia (HT). Methods: Secondary analysis of two multicenter treatment trials for either SH or HT diagnosed between 8 and 20 weeks gestation. Current analyses focus only on individuals randomized to the placebo groups in the two parallel studies. SH was diagnosed with thyrotropin (TSH) ≥4.0 mU/L and normal free T4 (fT4) (0.86-1.9 ng/dL). HT was diagnosed with normal TSH (0.08-3.99 mU/L) but fT4 <0.86 ng/dL. Serum from initial testing was stored for later thyroid peroxidase (TPO) antibody assay; results were not returned for clinical management. At 1 and 5 years after delivery, participants were asked whether they had either been diagnosed with or were being treated for a thyroid condition. Maternal serum was collected at these visits and thyroid function measured. Subsequent overt hypothyroidism was defined as TSH ≥4.0 mU/L with fT4 <0.86 ng/dL. Results: Data for 1- and 5-year follow-up were available in 307 of the 338 participants with SH and 229 of the 261 with HT. Subsequent hypothyroidism was more common both at year 1 (13.4% vs. 3.1%, p < 0.001) and year 5 (15.6% vs. 2.6%, p < 0.001) for participants with SH compared with those with HT. This progression was more common in individuals with TSH values >10 mIU/mL. Baseline TPO level >50 IU/mL in participants with SH was associated with higher rates of hypothyroidism at year 1 (26.7% vs. 6.5%, odds ratio [OR] = 5.3 [confidence interval (CI) 2.6-10.7]) and year 5 (30.5% vs. 7.5%, OR = 5.4 [CI: 2.8-10.6]) compared with those with TPO levels ≤50 IU/mL. For participants with HT, no differences in overt hypothyroidism were seen at 1 year related to baseline TPO level >50 IU/mL (1/10 (10%) vs. 6/218 (2.8%), OR = 3.9 [CI: 0.43-36.1]), but more participants with TPO levels >50 IU/mL developed hypothyroidism by year 5 (2/10 (20%) vs. 4/218 (1.8%), OR = 13.4 [CI: 2.1-84.1]). Conclusion: SH is associated with higher rates of overt hypothyroidism or thyroid replacement therapy within 5 years of delivery than is HT when these conditions are diagnosed in the first half of pregnancy.

Background: There are currently no validated clinical biomarkers of postacute sequelae of SARS-CoV-2 infection (PASC)., Objective: To investigate clinical laboratory markers of SARS-CoV-2 and PASC., Design: Propensity score-weighted linear regression models were fitted to evaluate differences in mean laboratory measures by prior infection and PASC index (≥12 vs. 0). (ClinicalTrials.gov: NCT05172024)., Setting: 83 enrolling sites., Participants: RECOVER-Adult cohort participants with or without SARS-CoV-2 infection with a study visit and laboratory measures 6 months after the index date (or at enrollment if >6 months after the index date). Participants were excluded if the 6-month visit occurred within 30 days of reinfection., Measurements: Participants completed questionnaires and standard clinical laboratory tests., Results: Among 10 094 participants, 8746 had prior SARS-CoV-2 infection, 1348 were uninfected, 1880 had a PASC index of 12 or higher, and 3351 had a PASC index of zero. After propensity score adjustment, participants with prior infection had a lower mean platelet count (265.9 × 10 9 cells/L [95% CI, 264.5 to 267.4 × 10 9 cells/L]) than participants without known prior infection (275.2 × 10 9 cells/L [CI, 268.5 to 282.0 × 10 9 cells/L]), as well as higher mean hemoglobin A 1c (HbA 1c ) level (5.58% [CI, 5.56% to 5.60%] vs. 5.46% [CI, 5.40% to 5.51%]) and urinary albumin-creatinine ratio (81.9 mg/g [CI, 67.5 to 96.2 mg/g] vs. 43.0 mg/g [CI, 25.4 to 60.6 mg/g]), although differences were of modest clinical significance. The difference in HbA 1c levels was attenuated after participants with preexisting diabetes were excluded. Among participants with prior infection, no meaningful differences in mean laboratory values were found between those with a PASC index of 12 or higher and those with a PASC index of zero., Limitation: Whether differences in laboratory markers represent consequences of or risk factors for SARS-CoV-2 infection could not be determined., Conclusion: Overall, no evidence was found that any of the 25 routine clinical laboratory values assessed in this study could serve as a clinically useful biomarker of PASC., Primary Funding Source: National Institutes of Health., Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M24-0737.

Objective: To estimate the prevalence of post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC) after infection with SARS-CoV-2 during pregnancy and to characterize associated risk factors., Methods: In a multicenter cohort study (NIH RECOVER [Researching COVID to Enhance Recovery]-Pregnancy Cohort), individuals who were pregnant during their first SARS-CoV-2 infection were enrolled across the United States from December 2021 to September 2023, either within 30 days of their infection or at differential time points thereafter. The primary outcome was PASC , defined as score of 12 or higher based on symptoms and severity as previously published by the NIH RECOVER-Adult Cohort, at the first study visit at least 6 months after the participant's first SARS-CoV-2 infection. Risk factors for PASC were evaluated, including sociodemographic characteristics, clinical characteristics before SARS-CoV-2 infection (baseline comorbidities, trimester of infection, vaccination status), and acute infection severity (classified by need for oxygen therapy). Multivariable logistic regression models were fitted to estimate associations between these characteristics and presence of PASC., Results: Of the 1,502 participants, 61.1% had their first SARS-CoV-2 infection on or after December 1, 2021 (ie, during Omicron variant dominance); 51.4% were fully vaccinated before infection; and 182 (12.1%) were enrolled within 30 days of their acute infection. The prevalence of PASC was 9.3% (95% CI, 7.9-10.9%) measured at a median of 10.3 months (interquartile range 6.1-21.5) after first infection. The most common symptoms among individuals with PASC were postexertional malaise (77.7%), fatigue (76.3%), and gastrointestinal symptoms (61.2%). In a multivariable model, the proportion PASC positive with vs without history of obesity (14.9% vs 7.5%, adjusted odds ratio [aOR] 1.65, 95% CI, 1.12-2.43), depression or anxiety disorder (14.4% vs 6.1%, aOR 2.64, 95% CI, 1.79-3.88) before first infection, economic hardship (self-reported difficulty covering expenses) (12.5% vs 6.9%, aOR 1.57, 95% CI, 1.05-2.34), and treatment with oxygen during acute SARS-CoV-2 infection (18.1% vs 8.7%, aOR 1.86, 95% CI, 1.00-3.44) were associated with increased prevalence of PASC., Conclusion: The prevalence of PASC at a median time of 10.3 months after SARS-CoV-2 infection during pregnancy was 9.3% in the NIH RECOVER-Pregnancy Cohort. The predominant symptoms were postexertional malaise, fatigue, and gastrointestinal symptoms. Several socioeconomic and clinical characteristics were associated with PASC after infection during pregnancy., Clinical Trial Registration: ClinicalTrials.gov , NCT05172024., Competing Interests: Financial Disclosure Torri D. Metz is the site PI for a Pfizer study of Paxlovid in pregnancy and was the site PI for a Pfizer study of COVID-19 vaccination in pregnancy. She has received UpToDate royalties for two topics on trial of labor after cesarean. Carmen J. Beamon disclosed receiving payments from Wellcare of North Carolina. Ann Chang's institution received payment from New York University for her efforts on this study. Kelly S. Gibson disclosed that her institution received funding from the NICHD, NHLBI, and Materna. Rachel Hess received payment from Astellas Pharmaceuticals. M. Camile Hoffman disclosed her institution received payment for her expert testimony for one medicolegal trial from Wheeler, Trigg, and Associates (a defense attorneys firm). Her institution also received payment for a disease state presentation on postpartum depression and zuranolone from SAGE/Biogen. Brenna L. Hughes disclosed receiving payments from UpToDate and Moderna. Stuart Katz disclosed payments for providing expert testimony for Venable LLP. Jennifer Hadlock has received funding (paid to institution) for retrospective studies of COVID-19 from Pfizer, Novartis, Janssen, and Gilead. Grace A. McComsey served as an advisor for Gilead and ViiVGlaxoSmithKline. Patrick Ramsey disclosed receiving royalties from UpToDate. His institution was paid by the Texas Collaborative for Healthy Mothers and Babies (TCHMB)—Texas PQC for part of his efforts. Daniel W. Skupski reports receiving payments from Organon, Inc and Cooper Surgical. Alan T.N. Tita disclosed money paid to his institution from Pfizer for his efforts in this study. Andrea Foulkes disclosed receiving past payments from Round Table, Inc. The other authors did not report any potential conflicts of interest., (Copyright © 2024 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

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., Competing Interests: Financial Disclosure Unrelated to this work, Marcela C. Smid reports that she serves as a consultant for Gilead Science Inc and Alydia/Organon. Her institution receives research funding from both organizations. Rebecca Clifton reports payment from the University of Arkansas for Medical Sciences for DSMB reviews. Sindhu Srinivas reports receiving payments from Goodall, Decries, Leech & Dawn, LLP, and Huff Powell Bailey. Ruth Landau reports receiving payments from PACIRA Biosciences and Regional Anesthesia and Pain Medicine. Cora MacPherson reports receiving payments from PCORI and Natera. The other authors did not report any potential conflicts of interest., (Copyright © 2024 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To systematically review the evidence for the effectiveness and safety of magnesium sulfate as a fetal neuroprotective agent when given to individuals at risk of preterm birth., Data Sources: We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov , the World Health Organization International Clinical Trials Registry Platform (through March 17, 2023), and reference lists of relevant studies., Methods of Study Selection: Randomized controlled trials (RCTs) assessing magnesium sulfate for fetal neuroprotection in pregnant participants at risk of imminent preterm birth were eligible. Two authors assessed RCTs for inclusion, extracted data, and evaluated risk of bias, trustworthiness, and evidence certainty (GRADE [Grading of Recommendations Assessment, Development and Evaluation])., Tabulation, Integration, and Results: We included six RCTs (5,917 pregnant participants and 6,759 fetuses at less than 34 weeks of gestation at randomization). They were conducted in high-income countries (two in the United States, two across Australia and New Zealand, and one each in Denmark and France) and commenced between 1995 and 2018. Primary outcomes: up to 2 years of corrected age, magnesium sulfate compared with placebo reduced the risk of cerebral palsy (risk ratio [RR] 0.71, 95% CI, 0.57-0.89; six RCTs, 6,107 children) and death or cerebral palsy (RR 0.87, 95% CI, 0.77-0.98; six RCTs, 6,481 children) (high-certainty evidence). Magnesium sulfate had little or no effect on death up to 2 years of corrected age (moderate-certainty evidence) or these outcomes at school age (low-certainty evidence). Although there was little or no effect on death or cardiac or respiratory arrest for pregnant individuals (low-certainty evidence), magnesium sulfate increased adverse effects severe enough to stop treatment (RR 3.21, 95% CI, 1.88-5.48; three RCTs, 4,736 participants; moderate-certainty evidence). Secondary outcome: magnesium sulfate reduced the risk of severe neonatal intraventricular hemorrhage (moderate-certainty evidence)., Conclusion: Magnesium sulfate for preterm fetal neuroprotection reduces cerebral palsy and death or cerebral palsy for children. Further research is required on longer-term benefits and harms for children, effect variation by participant and treatment characteristics, and the generalizability of findings to low- and middle-income countries., Systematic Review Registration: The review protocol was based on a standard Cochrane Pregnancy and Childbirth template and our previous Cochrane Systematic Review (doi: 10.1002/14651858.CD004661.pub3 ; published before the introduction of PROSPERO)., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Recent data in nonpregnant individuals suggest a protective effect of influenza vaccination against SARS-CoV-2 infection and its severity., Objectives: Our primary objective was to evaluate whether influenza vaccination was associated with COVID-19 severity and pregnancy and neonatal outcomes among those infected with SARS-CoV-2. The secondary objective was to examine the association between influenza vaccination and SARS-CoV-2 infection., Study Design: Secondary analysis of a multicenter retrospective cohort of pregnant people who tested positive for SARS-CoV-2 between March and August 2020, and a cohort of random deliveries during the same time period. The associations between 2019 influenza vaccination and the primary outcome of moderate-to-critical COVID-19 as well as maternal and perinatal outcomes were examined among all people who tested positive for SARS-CoV-2 between March and August 2020. The association between 2019 influenza vaccination and having a positive SARS-CoV-2 test was examined among a cohort of individuals who delivered on randomly selected dates between March and August 2020. Univariable and multivariable analyses were performed., Results: Of 2325 people who tested positive for SARS-CoV-2, 1068 (45.9%) were vaccinated against influenza in 2019. Those who received the influenza vaccine were older, leaner, more likely to have private insurance, and identify as White or Hispanic. They were less likely to smoke tobacco and identify as Black. Overall, 419 (18.0%) had moderate, 193 (8.3%) severe, and 52 (2.2%) critical COVID-19. There was no association between influenza vaccination and moderate-to-critical COVID-19 (29.2% vs. 28.0%, adjusted OR 1.10, 95% CI 0.90-1.34) or adverse maternal and perinatal outcomes among those who tested positive. Of 8152 people who delivered in 2020, 4658 (57.1%) received the influenza vaccine. Prior vaccination was not associated with a difference in the odds of SARS-CoV-2 infection (3.8% vs. 4.2%, adjusted OR 0.94, 95% CI 0.74-1.19)., Conclusion: Prior influenza vaccination was not associated with decreased severity of COVID-19 or lower odds of SARS-CoV-2 infection in pregnancy., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Venous thromboembolism accounts for approximately 9% of pregnancy-related deaths in the United States. National guidelines recommend postpartum risk stratification and pharmacologic prophylaxis in at-risk individuals. Knowledge on modern rates of postpartum pharmacologic thromboprophylaxis and its associated risks is limited., Objective: This study aimed to describe the rate of, and factors associated with, initiation of postpartum pharmacologic prophylaxis for venous thromboembolism, and to assess associated adverse outcomes., Study Design: This was a secondary analysis of a multicenter cohort of individuals delivering on randomly selected days at 17 US hospitals (2019-2020). Medical records were reviewed by trained and certified personnel. Those with an antepartum diagnosis of venous thromboembolism, receiving antepartum anticoagulation, or known SARS-CoV-2 infection were excluded. The primary outcome was use of postpartum pharmacologic thromboprophylaxis. Secondary outcomes included bleeding complications, surgical site infection, hospital readmission, and venous thromboembolism through 6 weeks postpartum. The rate of thromboprophylaxis administration was assessed by mode of delivery, institution, and continuance to the outpatient setting. Multivariable regression models were developed using k-fold cross-validation with stepwise backward elimination to evaluate factors associated with thromboprophylaxis administration. Univariable and multivariable logistic models with propensity score covariate adjustment were performed to assess the association between thromboprophylaxis administration and adverse outcomes., Results: Of 21,114 individuals in the analytical cohort, 11.9% (95% confidence interval, 11.4%-12.3%) received postpartum pharmacologic thromboprophylaxis; the frequency of receipt was 29.8% (95% confidence interval, 28.7%-30.9%) following cesarean and 3.5% (95% confidence interval, 3.2%-3.8%) following vaginal delivery. Institutional rates of prophylaxis varied from 0.21% to 34.8%. Most individuals (83.3%) received thromboprophylaxis only as inpatients. In adjusted analysis, cesarean delivery (adjusted odds ratio, 19.17; 95% confidence interval, 16.70-22.00), hysterectomy (adjusted odds ratio, 15.70; 95% confidence interval, 4.35-56.65), and obesity (adjusted odds ratio, 3.45; 95% confidence interval, 3.02-3.95) were the strongest factors associated with thromboprophylaxis administration. Thromboprophylaxis administration was not associated with surgical site infection (0.9% vs 0.6%; odds ratio, 1.48; 95% confidence interval, 0.80-2.74), bleeding complications (0.2% vs 0.1%; odds ratio, 2.60; 95% confidence interval, 0.99-6.80), or postpartum readmission (0.9% vs 0.3%; adjusted odds ratio, 1.38; 95% confidence interval, 0.68-2.81). The overall rate of venous thromboembolism was 0.06% (95% confidence interval, 0.03%-0.10%) and was higher in those receiving prophylaxis (0.2%) compared with those not receiving prophylaxis (0.04%)., Conclusion: Approximately 1 in 10 patients received postpartum pharmacologic thromboprophylaxis in this US cohort. Rates of prophylaxis varied widely by institution. Cesarean delivery, hysterectomy, and obesity were predominant factors associated with postpartum thromboprophylaxis administration., (Copyright © 2023. Published by Elsevier Inc.)

Objective: We sought to (1) use the Robson 10-Group Classification System (TGCS), which classifies deliveries into 10 mutually exclusive groups, to characterize the groups that are primary contributors to cesarean delivery frequencies, (2) describe inter-hospital variations in cesarean delivery frequencies, and (3) evaluate the contribution of patient characteristics by TGCS group to hospital variation in cesarean delivery frequencies., Study Design: This was a secondary analysis of an observational cohort of 115,502 deliveries from 25 hospitals between 2008 and 2011. The TGCS was applied to the cohort and each hospital. We identified and compared the TGCS groups with the greatest relative contributions to cohort and hospital cesarean delivery frequencies. We assessed variation in hospital cesarean deliveries attributable to patient characteristics within TGCS groups using hierarchical logistic regression., Results: A total of 115,211 patients were classifiable in the TGCS (99.7%). The cohort cesarean delivery frequency was 31.4% (hospital range: 19.1-39.3%). Term singletons in vertex presentation with a prior cesarean delivery (group 5) were the greatest relative contributor to cohort (34.8%) and hospital cesarean delivery frequencies (median: 33.6%; range: 23.8-45.5%). Nulliparous term singletons in vertex (NTSV) presentation (groups 1 [spontaneous labor] and 2 [induced or absent labor]: 28.9%), term singletons in vertex presentation with a prior cesarean delivery (group 5: 34.8%), and preterm singletons in vertex presentation (group 10: 9.8%) contributed to 73.2% of the relative cesarean delivery frequency for the cohort and were correlated with hospital cesarean delivery frequencies (Spearman's rho = 0.96). Differences in patient characteristics accounted for 34.1% of hospital-level cesarean delivery variation in group 2., Conclusion: The TGCS highlights the contribution of NTSV presentation to cesarean delivery frequencies and the impact of patient characteristics on hospital-level variation in cesarean deliveries among nulliparous patients with induced or absent labor., Key Points: · We report on the cesarean delivery frequencies in a multicenter U.S., Cohort: . · NTSV gestations (groups 1 and 2) are a primary driver of cesarean deliveries.. · Patient characteristics contributed most to hospital variation in cesarean deliveries in group 2.., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective:  This study aimed to test the hypothesis that being pregnant and delivering during the coronavirus disease 2019 (COVID-19) pandemic was associated with changes in gestational weight gain (GWG) or frequency of small- (SGA) or large-for-gestational-age (LGA) neonates., Study Design:  Secondary analysis of a multicenter observational cohort comparing pregnant people who delivered during the COVID-19 pandemic (June-December 2020) to people who delivered prior to the pandemic (March-December 2019). Those with multiple gestations, fetuses with major congenital anomalies, implausible GWG values, unavailable body mass index (BMI), or who were severe acute respiratory syndrome coronavirus-2-positive were excluded. The primary outcome was frequency of optimal recommended GWG based on prepregnancy BMI. Neonatal outcomes included birth weight, ponderal index, and frequency of SGA, LGA, and small head circumference for live births. Multivariable regression analysis was used to assess associations between exposure to the pandemic and outcomes., Results:  A total of 10,717 pregnant people were included in our analysis. A total of 4,225 pregnant people were exposed to the pandemic and 6,492 pregnant people delivered prior to the COVID-19 pandemic. Pregnant people exposed to the pandemic were older and more likely to have gestational diabetes. The frequency of appropriate GWG was 28.0% during the pandemic and 27.6% before the pandemic (adjusted odds ratio [aOR]: 1.02, 95% confidence interval [CI]: 0.93-1.11). Excessive GWG was more likely (54.9 vs. 53.1%; aOR: 1.08, 95% CI: 1.001-1.17), and inadequate GWG was less likely during the pandemic (17.0 vs. 19.3%; aOR: 0.86, 95% CI: 0.77-0.95). The frequency of SGA was 5.4% during the pandemic and 6.1% before the pandemic (aOR: 0.90, 95% CI: 0.76-1.06), and the frequency of LGA was 16.0% during the pandemic versus 15.0% before the pandemic (aOR: 1.06, 95% CI: 0.95-1.18). Other neonatal outcomes including birth weight percentile (62.1 [35.8-83.2] vs. 60.2 [34.4-82.2]; adjusted mean difference (aMD) = 1.50, 95% CI: -0.28 to 3.29), ponderal index (2.6 g/cm 3 [2.4-2.8] in both groups; aMD = 0.01, 95% CI: 0.00-0.02), and small head circumference for livebirths (<10th percentile [8.2 vs. 8.1%; aOR: 1.03, 95% CI: 0.89-1.19], <3rd percentile [3.5 vs. 3.1%; aOR: 1.16, 95% CI: 0.93-1.44]) were similar between groups as well., Conclusion:  Being pregnant and delivering during the COVID-19 pandemic was associated with a higher likelihood of excessive GWG and a lower likelihood of inadequate GWG., Key Points: · Delivering during the COVID-19 pandemic was associated with higher likelihood of excessive GWG.. · Delivering during the COVID-19 pandemic was associated with lower likelihood of inadequate GWG.. · COVID-19 pandemic was not associated with changes in frequency of SGA or LGA.., Competing Interests: None declared., (Thieme. All rights reserved.)

The BEAM Trial., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

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.

Background: Magnesium sulphate is a common therapy in perinatal care. Its benefits when given to women at risk of preterm birth for fetal neuroprotection (prevention of cerebral palsy for children) were shown in a 2009 Cochrane review. Internationally, use of magnesium sulphate for preterm cerebral palsy prevention is now recommended practice. As new randomised controlled trials (RCTs) and longer-term follow-up of prior RCTs have since been conducted, this review updates the previously published version., Objectives: To assess the effectiveness and safety of magnesium sulphate as a fetal neuroprotective agent when given to women considered to be at risk of preterm birth., Search Methods: We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) on 17 March 2023, as well as reference lists of retrieved studies., Selection Criteria: We included RCTs and cluster-RCTs of women at risk of preterm birth that assessed prenatal magnesium sulphate for fetal neuroprotection compared with placebo or no treatment. All methods of administration (intravenous, intramuscular, and oral) were eligible. We did not include studies where magnesium sulphate was used with the primary aim of preterm labour tocolysis, or the prevention and/or treatment of eclampsia., Data Collection and Analysis: Two review authors independently assessed RCTs for inclusion, extracted data, and assessed risk of bias and trustworthiness. Dichotomous data were presented as summary risk ratios (RR) with 95% confidence intervals (CI), and continuous data were presented as mean differences with 95% CI. We assessed the certainty of the evidence using the GRADE approach., Main Results: We included six RCTs (5917 women and their 6759 fetuses alive at randomisation). All RCTs were conducted in high-income countries. The RCTs compared magnesium sulphate with placebo in women at risk of preterm birth at less than 34 weeks' gestation; however, treatment regimens and inclusion/exclusion criteria varied. Though the RCTs were at an overall low risk of bias, the certainty of evidence ranged from high to very low, due to concerns regarding study limitations, imprecision, and inconsistency. Primary outcomes for infants/children: Up to two years' corrected age, magnesium sulphate compared with placebo reduced cerebral palsy (RR 0.71, 95% CI 0.57 to 0.89; 6 RCTs, 6107 children; number needed to treat for additional beneficial outcome (NNTB) 60, 95% CI 41 to 158) and death or cerebral palsy (RR 0.87, 95% CI 0.77 to 0.98; 6 RCTs, 6481 children; NNTB 56, 95% CI 32 to 363) (both high-certainty evidence). Magnesium sulphate probably resulted in little to no difference in death (fetal, neonatal, or later) (RR 0.96, 95% CI 0.82 to 1.13; 6 RCTs, 6759 children); major neurodevelopmental disability (RR 1.09, 95% CI 0.83 to 1.44; 1 RCT, 987 children); or death or major neurodevelopmental disability (RR 0.95, 95% CI 0.85 to 1.07; 3 RCTs, 4279 children) (all moderate-certainty evidence). At early school age, magnesium sulphate may have resulted in little to no difference in death (fetal, neonatal, or later) (RR 0.82, 95% CI 0.66 to 1.02; 2 RCTs, 1758 children); cerebral palsy (RR 0.99, 95% CI 0.69 to 1.41; 2 RCTs, 1038 children); death or cerebral palsy (RR 0.90, 95% CI 0.67 to 1.20; 1 RCT, 503 children); and death or major neurodevelopmental disability (RR 0.81, 95% CI 0.59 to 1.12; 1 RCT, 503 children) (all low-certainty evidence). Magnesium sulphate may also have resulted in little to no difference in major neurodevelopmental disability, but the evidence is very uncertain (average RR 0.92, 95% CI 0.53 to 1.62; 2 RCTs, 940 children; very low-certainty evidence). Secondary outcomes for infants/children: Magnesium sulphate probably reduced severe intraventricular haemorrhage (grade 3 or 4) (RR 0.76, 95% CI 0.60 to 0.98; 5 RCTs, 5885 infants; NNTB 92, 95% CI 55 to 1102; moderate-certainty evidence) and may have resulted in little to no difference in chronic lung disease/bronchopulmonary dysplasia (average RR 0.92, 95% CI 0.77 to 1.10; 5 RCTs, 6689 infants; low-certainty evidence). Primary outcomes for women: Magnesium sulphate may have resulted in little or no difference in severe maternal outcomes potentially related to treatment (death, cardiac arrest, respiratory arrest) (RR 0.32, 95% CI 0.01 to 7.92; 4 RCTs, 5300 women; low-certainty evidence). However, magnesium sulphate probably increased maternal adverse effects severe enough to stop treatment (average RR 3.21, 95% CI 1.88 to 5.48; 3 RCTs, 4736 women; moderate-certainty evidence). Secondary outcomes for women: Magnesium sulphate probably resulted in little to no difference in caesarean section (RR 0.96, 95% CI 0.91 to 1.02; 5 RCTs, 5861 women) and postpartum haemorrhage (RR 0.94, 95% CI 0.80 to 1.09; 2 RCTs, 2495 women) (both moderate-certainty evidence). Breastfeeding at hospital discharge and women's views of treatment were not reported., Authors' Conclusions: The currently available evidence indicates that magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus, compared with placebo, reduces cerebral palsy, and death or cerebral palsy, in children up to two years' corrected age, and probably reduces severe intraventricular haemorrhage for infants. Magnesium sulphate may result in little to no difference in outcomes in children at school age. While magnesium sulphate may result in little to no difference in severe maternal outcomes (death, cardiac arrest, respiratory arrest), it probably increases maternal adverse effects severe enough to stop treatment. Further research is needed on the longer-term benefits and harms for children, into adolescence and adulthood. Additional studies to determine variation in effects by characteristics of women treated and magnesium sulphate regimens used, along with the generalisability of findings to low- and middle-income countries, should be considered., (Copyright © 2024 The Authors. Cochrane Database of Systematic Reviews published by John Wiley & Sons, Ltd. on behalf of The Cochrane Collaboration.)

Objective: The aim of this study was to evaluate whether being small for gestational age (SGA) or large for gestational age (LGA) or having a small or large head circumference (HC) at birth is associated with adverse neurodevelopmental outcomes., Study Design: This is a secondary analysis of a multicenter negative randomized trial of thyroxine therapy for subclinical hypothyroid disorders in pregnancy. The primary outcome was child intelligence quotient (IQ) at 5 years of age. Secondary outcomes included several neurodevelopmental measures. Associations between the outcomes in children with SGA (<10th percentile) or LGA (>90th percentile) birth weights, using ethnicity- and sex-specific population nomogram as well as nomograms from the National Fetal Growth (NFG) study, were compared with the referent of those with appropriate for gestational age (AGA) birth weight. Similar analyses were performed for HC., Results: Using the population nomogram, 90 (8.2%) were SGA and 112 (10.2%) were LGA. SGA neonates were more likely to be born preterm to mothers who were younger, smoked, and were less likely to have less than a high school education, whereas LGA neonates were more likely to be born to mothers who were older and have higher body mass index, compared with AGA neonates. SGA at birth was associated with a decrease in the child IQ at 5 years of age by 3.34 (95% confidence interval [CI], 0.54-6.14) points, and an increase in odds of child with an IQ < 85 (adjusted odds ratio [aOR], 1.9; 95% CI, 1.1-3.2). There was no association between SGA and other secondary outcomes, or between LGA and the primary or secondary outcomes. Using the NFG standards, SGA at birth remained associated with a decrease in the child IQ at 5 years of age by 3.14 (95% CI, 0.22-6.05) points and higher odds of an IQ < 85 (aOR, 2.3; 95% CI, 1.3-4.1), but none of the other secondary outcomes. HC was not associated with the primary outcome, and there were no consistent associations of these standards with the secondary outcomes., Conclusion: In this cohort of pregnant individuals with hypothyroid disorders, SGA birth weight was associated with a decrease in child IQ and greater odds of child IQ < 85 at 5 years of age. Using a fetal growth standard did not appear to improve the detection of newborns at risk of adverse neurodevelopment., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective: Our objective was to evaluate whether iodine status in pregnant patients with either subclinical hypothyroidism or hypothyroxinemia in the first half of pregnancy is associated with measures of behavior and neurodevelopment in children through the age of 5 years., Study Design: This is a secondary analysis of a multicenter study consisting of two randomized, double-masked, placebo-controlled treatment trials conducted in parallel. Patients with a singleton gestation before 20 weeks' gestation underwent thyroid screening using serum thyrotropin and free thyroxine. Participants with subclinical hypothyroidism or hypothyroxinemia were randomized to levothyroxine replacement or an identical placebo. At randomization, maternal urine was collected and stored for subsequent urinary iodine excretion analysis. Urinary iodine concentrations greater than 150 μg/L were considered iodine sufficient, and concentrations of 150 μg/L or less were considered iodine insufficient. The primary outcome was a full-scale intelligence quotient (IQ) score at the age of 5 years, the general conceptual ability score from the Differential Ability Scales-II at the age of 3 if IQ was not available, or death before 3 years., Results: A total of 677 pregnant participants with subclinical hypothyroidism and 526 with hypothyroxinemia were randomized. The primary outcome was available in 1,133 (94%) of children. Overall, 684 (60%) of mothers were found to have urinary iodine concentrations >150 μg/L. Children of iodine-sufficient participants with subclinical hypothyroidism had similar primary outcome scores when compared to children of iodine-insufficient participants (95 [84-105] vs. 96 [87-109], P adj  = 0.73). After adjustment, there was also no difference in IQ scores among children of participants with hypothyroxinemia at 5 to 7 years of age (94 [85 - 102] and 91 [81 - 100], P adj 1/4 0.11). Treatment with levothyroxine was not associated with neurodevelopmental or behavioral outcomes regardless of maternal iodine status ( p  > 0.05)., Conclusion: Maternal urinary iodine concentrations ≤150 μg/L were not associated with abnormal cognitive or behavioral outcomes in offspring of participants with either subclinical hypothyroidism or hypothyroxinemia., Key Points: · Most pregnant patients with subclinical thyroid disease are iodine sufficient.. · Mild maternal iodine insufficiency is not associated with lower offspring IQ at 5 years.. · Iodine supplementation in subclinical thyroid disease is unlikely to improve IQ.., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective: Administration of antenatal corticosteroids (ANCS) is recommended for individuals expected to deliver between 24 and 34 weeks of gestation. Properly timed administration of ANCS achieves maximal benefit. However, more than 50% of individuals receive ANCS outside the recommended window. This study aimed to examine maternal and hospital factors associated with suboptimal receipt of ANCS among individuals who deliver between 24 and 34 weeks of gestation., Study Design: Secondary analysis of the Assessment of Perinatal Excellence (APEX), an observational study of births to 115,502 individuals at 25 hospitals in the United States from March 2008 to February 2011, was conducted. Data from 3,123 individuals who gave birth to a nonanomalous live-born infant between 24 0/7 to 34 0/7 weeks of gestation, had prenatal records available at delivery, and data available on the timing of ANCS use were included in this analysis. Eligible individuals' ANCS status was categorized as optimal (full course completed >24 hours after ANCS but not >7 days before birth) or suboptimal (none, too late, or too early). Maternal and hospital-level variables were compared using optimal as the referent group. Hierarchical multinomial logistic regression models, with site as a random effect, were used to identify maternal and hospital-level characteristics associated with optimal ANCS use., Results: Overall, 83.6% (2,612/3,123) of eligible individuals received any treatment: 1,216 (38.9%) optimal and 1,907 (61.1%) suboptimal. Within suboptimal group, 495 (15.9%) received ANCS too late, 901 (28.9%) too early, and 511 (16.4%) did not receive any ANCS. Optimal ANCS varied depending on indication for hospital admission ( p  < 0.001). Individuals who were admitted with intent to deliver were less likely to receive optimal ANCS while individuals admitted for hypertensive diseases of pregnancy were most likely to receive optimal ANCS (10 vs. 35%). The median gestational age of individuals who received optimal ANCS was 31.0 weeks. Adjusting for hospital factors, hospitals with electronic medical records and who receive transfers have fewer eligible individuals who did not receive ANCS. ANCS administration and timing varied substantially by hospital, optimal frequencies ranged from 9.1 to 51.3%, and none frequencies from 6.1 to 61.8%. When evaluating variation by hospital site, models with maternal and hospital factors did not explain any of the variation in ANCS use., Conclusion: Optimal ANCS use varied by maternal and hospital factors and by hospital site, indicating opportunities for improvement., Key Points: · Majority of individuals who deliver between 24 and 34 weeks of gestation do not receive properly timed antenatal corticosteroids.. · Optimal use of antenatal corticosteroids varies by maternal and hospital factors and hospital site.. · Significant variation in hospital sites regarding optimally timed administration of antenatal corticosteroids indicates opportunities for improvement.., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective: This study aimed to evaluate whether there are genetic variants associated with adverse neurodevelopmental outcomes in extremely low birth weight (ELBW) infants., Study Design: We conducted a candidate gene association study in two well-defined cohorts of ELBW infants (<1,000 g). One cohort was for discovery and the other for replication. The discovery case-control analysis utilized anonymized DNA samples and evaluated 1,614 single-nucleotide polymorphisms (SNPs) in 145 genes concentrated in inflammation, angiogenesis, brain development, and oxidation pathways. Cases were children who died by age one or who were diagnosed with cerebral palsy (CP) or neurodevelopmental delay (Bayley II mental developmental index [MDI] or psychomotor developmental index [PDI] < 70) by 18 to 22 months. Controls were survivors with normal neurodevelopment. We assessed significant epidemiological variables and SNPs associated with the combined outcome of CP or death, CP, mental delay (MDI < 70) and motor delay (PDI < 70). Multivariable analyses adjusted for gestational age at birth, small for gestational age, sex, antenatal corticosteroids, multiple gestation, racial admixture, and multiple comparisons. SNPs associated with adverse neurodevelopmental outcomes with p  < 0.01 were selected for validation in the replication cohort. Successful replication was defined as p  < 0.05 in the replication cohort., Results: Of 1,013 infants analyzed (452 cases, 561 controls) in the discovery cohort, 917 were successfully genotyped for >90% of SNPs and passed quality metrics. After adjusting for covariates, 26 SNPs with p  < 0.01 for one or more outcomes were selected for replication cohort validation, which included 362 infants (170 cases and 192 controls). A variant in SERPINE1, which encodes plasminogen activator inhibitor (PAI1), was associated with the combined outcome of CP or death in the discovery analysis ( p  = 4.1 × 10 -4 ) and was significantly associated with CP or death in the replication cohort (adjusted odd ratio: 0.4; 95% confidence interval: 0.2-1.0; p  = 0.039)., Conclusion: A genetic variant in SERPINE1, involved in inflammation and coagulation, is associated with CP or death among ELBW infants., Key Points: · Early preterm and ELBW infants have dramatically increased risks of CP and developmental delay.. · A genetic variant in SERPINE1 is associated with CP or death among ELBW infants.. · The SERPINE1 gene encodes the serine protease inhibitor plasminogen activator inhibitor.., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective: This study aimed to measure the association between hypertensive disorders of pregnancy (HDP) and long-term maternal metabolic and cardiovascular biomarkers., Study Design: Follow-up study of patients who completed glucose tolerance testing 5 to 10 years after enrollment in a mild gestational diabetes mellitus (GDM) treatment trial or concurrent non-GDM cohort. Maternal serum insulin concentrations and cardiovascular markers VCAM-1, VEGF, CD40L, GDF-15, and ST-2 were measured, and insulinogenic index (IGI, pancreatic β-cell function) and 1/ homeostatic model assessment (insulin resistance) were calculated. Biomarkers were compared by presence of HDP (gestational hypertension or preeclampsia) during pregnancy. Multivariable linear regression estimated the association of HDP with biomarkers, adjusting for GDM, baseline body mass index (BMI), and years since pregnancy., Results: Of 642 patients, 66 (10%) had HDP: 42 with gestational hypertension and 24 with preeclampsia. Patients with HDP had higher baseline and follow-up BMI, higher baseline blood pressure, and more chronic hypertension at follow-up. HDP was not associated with metabolic or cardiovascular biomarkers at follow-up. However, when HDP type was evaluated, patients with preeclampsia had lower GDF-15 levels (oxidative stress/cardiac ischemia), compared with patients without HDP (adjusted mean difference: -0.24, 95% confidence interval: -0.44, -0.03). There were no differences between gestational hypertension and no HDP., Conclusion: In this cohort, metabolic and cardiovascular biomarkers 5 to 10 years after pregnancies did not differ by HDP. Patients with preeclampsia may have less oxidative stress/cardiac ischemia postpartum; however, this may have been observed due to chance alone given multiple comparisons. Longitudinal studies are needed to define the impact of HDP during pregnancy and interventions postpartum., Key Points: · Hypertensive disorders of pregnancy were not associated with metabolic dysfunction.. · Cardiovascular dysfunction was not consistently seen after pregnancy hypertension.. · Longitudinal studies with postpartum interventions after preeclampsia are needed.., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective: Prediction of blood transfusion during delivery admission allows for clinical preparedness and risk mitigation. Although prediction models have been developed and adopted into practice, their external validation is limited. We aimed to evaluate the performance of three blood transfusion prediction models in a U.S. cohort of individuals undergoing cesarean delivery., Study Design: This was a secondary analysis of a multicenter randomized trial of tranexamic acid for prevention of hemorrhage at time of cesarean delivery. Three models were considered: a categorical risk tool (California Maternal Quality Care Collaborative [CMQCC]) and two regression models (Ahmadzia et al and Albright et al). The primary outcome was intrapartum or postpartum red blood cell transfusion. The CMQCC algorithm was applied to the cohort with frequency of risk category (low, medium, high) and associated transfusion rates reported. For the regression models, the area under the receiver-operating curve (AUC) was calculated and a calibration curve plotted to evaluate each model's capacity to predict receipt of transfusion. The regression model outputs were statistically compared., Results: Of 10,785 analyzed individuals, 3.9% received a red blood cell transfusion during delivery admission. The CMQCC risk tool categorized 1,970 (18.3%) individuals as low risk, 5,259 (48.8%) as medium risk, and 3,556 (33.0%) as high risk with corresponding transfusion rates of 2.1% (95% confidence interval [CI]: 1.5-2.9%), 2.2% (95% CI: 1.8-2.6%), and 7.5% (95% CI: 6.6-8.4%), respectively. The AUC for prediction of blood transfusion using the Ahmadzia and Albright models was 0.78 (95% CI: 0.76-0.81) and 0.79 (95% CI: 0.77-0.82), respectively ( p  = 0.38 for difference). Calibration curves demonstrated overall agreement between the predicted probability and observed likelihood of blood transfusion., Conclusion: Three models were externally validated for prediction of blood transfusion during cesarean delivery admission in this U.S., Cohort: Overall, performance was moderate; model selection should be based on ease of application until a specific model with superior predictive ability is developed., Key Points: · A total of 3.9% of individuals received a blood transfusion during cesarean delivery admission.. · Three models used in clinical practice are externally valid for blood transfusion prediction.. · Institutional model selection should be based on ease of application until further research identifies the optimal approach.., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective: We have previously described a model using maternal, antenatal, and ultrasonographic characteristics to assess the risk of delivery within 7 days following diagnosis of abnormal umbilical artery Doppler (UAD) in pregnancies affected by fetal growth restriction (FGR). Therefore, we sought to validate this model in an independent cohort., Study Design: Retrospective, single referral center study of liveborn singleton pregnancies from 2016 to 2019 complicated by FGR and abnormal UAD (systolic/diastolic ratio ≥95th percentile for gestational age [GA]). Prediction probabilities were calculated by applying the original model (Model 1) to the current cohort (Brigham and Women's Hospital [BWH] cohort). The variables of this model include GA at first abnormal UAD, severity of first abnormal UAD, oligohydramnios, preeclampsia, and prepregnancy body mass index. Model fit was assessed with area under the curve (AUC). Two alternative models (Models 2 and 3) were created to identify a model with better predictive characteristics than Model 1. The receiver operating characteristics curves were compared using the DeLong test., Results: A total of 306 patients were assessed for eligibility, 223 of whom were included in the BWH cohort. Median GA at eligibility was 31.3 weeks, and median interval from eligibility to delivery was 17 days (interquartile range: 3.5-33.5). Eighty-two (37%) patients delivered within 7 days of eligibility. Applying Model 1 to the BWH cohort resulted in an AUC of 0.865. Using the previously determined probability cutoff of 0.493, the model was 62% sensitive and 90% specific in predicting the primary outcome in this independent cohort. Models 2 and 3 did not perform better than Model 1 ( p  = 0.459)., Conclusion: A previously described prediction model to predict risk of delivery in patients with FGR and abnormal UAD performed well in an independent cohort. With high specificity, this model could assist in identifying low-risk patients and improve antenatal corticosteroid timing., Key Points: · Risk of delivery in 7 days can be predicted.. · Risk of delivery can inform corticosteroid timing.. · An externally validated clinical aid can be developed.., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective: This study aimed to assess the association of maternal body mass index (BMI) with a composite of severe maternal outcomes., Study Design: Secondary analysis of a cohort of deliveries on randomly selected days at 25 hospitals from 2008 to 2011. Data on comorbid conditions, intrapartum events, and postpartum course were collected. The reference group (REF, BMI: 18.5-29.9kg/m 2 ), obese (OB; BMI: 30-39.9kg/m 2 ), morbidly obese (MO; BMI: 40-49.9kg/m 2 ), and super morbidly obese (SMO; BMI ≥ 50kg/m 2 ) women were compared. The composite of severe maternal outcomes was defined as death, intensive care unit (ICU) admission, ventilator use, deep venous thrombosis/pulmonary embolus (DVT/PE), sepsis, hemorrhage, disseminated intravascular coagulation (DIC), unplanned operative procedure, or stroke. Patients in the REF group were matched 1:1 with those in all other obesity groups based on propensity score using the baseline characteristics of age, race/ethnicity, previous cesarean, preexisting diabetes, chronic hypertension, parity, cigarette use, and insurance status. Multivariable Poisson's regression was used to estimate adjusted relative risks (aRRs) and 95% confidence intervals (CIs) for the association between BMI and the composite outcome. Because cesarean delivery may be in the causal pathway between obesity and adverse maternal outcomes, models were then adjusted for mode of delivery to evaluate potential mediation., Results: A total of 52,162 pregnant patients are included in the analysis. Risk of composite maternal outcomes was increased for SMO compared with REF but not for OB and MO [OB: aRR=1.06, 95% CI: 0.99-1.14; MO: aRR=1.10, 95% CI: 0.97-1.25; SMO: aRR=1.32, 95% CI: 1.02-1.70]. However, in the mediation analysis, cesarean appears to mediate 46% (95% CI: 31-50%) of the risk of severe morbidity for SMO compared with REF., Conclusion: Super morbid obesity is significantly associated with increased serious maternal morbidity and mortality; however, cesarean appears to mediate this association. Obesity and morbid obesity are not associated with maternal morbidity and mortality., Key Points: · Super morbid obesity is associated with increased morbidity.. · Cesarean appears to mediate the association between super morbid obesity and morbidity.. · Obesity and morbid maternal obesity are not associated with morbidity.., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective: Fetal electrocardiogram (ECG) ST changes are associated with fetal cardiac hypoxia. Our objective was to evaluate ST changes by maternal diabetic status and stage of labor., Methods: This was a secondary analysis of a multicentered randomized-controlled trial in which laboring patients with singleton gestations underwent fetal ECG scalp electrode placement and were randomly assigned to masked or unmasked ST-segment readings. Our primary outcome was the frequency of fetal ECG tracings with ST changes by the stage of labor. ECG tracings were categorized into mutually exclusive groups (ST depression, ST elevation without ST depression, or no ST changes). We compared participants with DM, gestational diabetes mellitus (GDM), and no DM., Results: Of the 5,436 eligible individuals in the first stage of labor (95 with pregestational DM and 370 with GDM), 4,427 progressed to the second stage. ST depression occurred more frequently in the first stage of labor in participants with pregestational DM (15%, adjusted odds ratio [aOR] 2.20, 95% confidence interval [CI] 1.14-4.24) and with GDM (9.5%, aOR 1.51, 95% CI 1.02-2.25) as compared with participants without DM (5.7%). The frequency of ST elevation was similar in participants with pregestational DM (33%, aOR 0.79, 95% CI 0.48-1.30) and GDM (33.2%, aOR 0.91, 95% CI 0.71-1.17) as compared with those without DM (34.2%). In the second stage, ST depression did not occur in participants with pregestational DM (0%) and occurred more frequently in participants with GDM (3.5%, aOR 2.01, 95% CI 1.02-3.98) as compared with those without DM (2.0%). ST elevation occurred more frequently in participants with pregestational DM (30%, aOR 1.81, 95% CI 1.02-3.22) but not with GDM (19.0%, aOR 1.06, 95% CI 0.77-1.47) as compared with those without DM (17.8%)., Conclusion: ST changes in fetal ECG occur more frequently in fetuses of diabetic mothers during labor., Clinicaltrials: gov number, NCT01131260., Precis: ST changes in fetal ECG, a marker of fetal cardiac hypoxia, occur more frequently in fetuses of diabetic parturients., Key Points: · Fetal hypertrophic cardiomyopathy (HCM) and cardiac dysfunction occur frequently among fetuses of diabetic patients.. · Fetal ECG changes such as ST elevation and depression reflect cardiac hypoxia.. · Fetuses of diabetic patients demonstrate a higher prevalence of fetal ECG tracings with ST changes.., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective: To assess whether neonatal morbidities evident by the time of hospital discharge are associated with subsequent cerebral palsy (CP) or death., Study Design: This is a secondary analysis of data from a multicenter placebo-controlled trial of magnesium sulfate for the prevention of CP. The association between prespecified intermediate neonatal outcomes ( n  = 11) and demographic and clinical factors ( n  = 10) evident by the time of discharge among surviving infants ( n  = 1889) and the primary outcome of death or moderate/severe CP at age 2 ( n  = 73) was estimated, and a prediction model was created., Results: Gestational age in weeks at delivery (odds ratio [OR]: 0.74, 95% confidence interval [CI]: 0.67-0.83), grade III or IV intraventricular hemorrhage (IVH) (OR: 5.3, CI: 2.1-13.1), periventricular leukomalacia (PVL) (OR: 46.4, CI: 20.6-104.6), and male gender (OR: 2.5, CI: 1.4-4.5) were associated with death or moderate/severe CP by age 2. Outcomes not significantly associated with the primary outcome included respiratory distress syndrome, bronchopulmonary dysplasia, seizure, necrotizing enterocolitis, neonatal hypotension, 5-minute Apgar score, sepsis, and retinopathy of prematurity. Using all patients, the receiver operating characteristic curve for the final prediction model had an area under the curve of 0.84 (CI: 0.78-0.89). Using these data, the risk of death or developing CP by age 2 can be calculated for individual surviving infants., Conclusion: IVH and PVL were the only neonatal complications evident at discharge that contributed to an individual infant's risk of the long-term outcomes of death or CP by age 2. A model that includes these morbidities, gestational age at delivery, and gender is predictive of subsequent neurologic sequelae., Key Points: · Factors known at hospital discharge are identified which are independently associated with death or CP by age 2.. · A model was created and validated using these findings to counsel parents.. · The risk of death or CP can be calculated at the time of hospital discharge.., Competing Interests: None declared., (Thieme. All rights reserved.)

Induction of labor is a widely used practice. From 2016 to 2019, >1 in 3 women giving birth in the United States did so after undergoing labor induction. The obvious goal of labor induction is vaginal birth with minimal maternal or neonatal morbidity. To achieve this goal, criteria for failed labor induction are needed. Herein, we provide an evidence-based approach to safely prevent unnecessary cesarean deliveries for failed induction. Although there are no randomized trials comparing failed labor induction criteria, the observational data have been consistent: if the status of the mother and the fetus permits, at least 12 to 18 hours of oxytocin should be administered after membrane rupture before deeming an induction of labor to have failed because of nonprogression to the active phase of labor., (Copyright © 2022 Elsevier Inc. All rights reserved.)

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., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Importance: 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., Methods: 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., Discussion: 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 Trials.gov Identifier: Clinical Trial Registration: http://www.clinicaltrials.gov. Unique identifier: NCT05172011., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Dr. Metz reports personal fees from Pfizer for her role as a medical consultant for a SARS-CoV-2 vaccination in pregnancy study, grants from Pfizer for role as a site PI for SARS-CoV-2 vaccination in pregnancy study, grants from Pfizer for role as a site PI for RSV vaccination in pregnancy study, and grants from Gestvision for role as a site PI for a preeclampsia study outside the submitted work. Dr. Horwitz reported serving as a member of the National Academy of Medicine Committee on the Long-Term Health Effects Stemming from COVID-19 and Implications for the Social Security Administration. Dr. Costantine reported receiving grant support for work not related to this paper from Baxter International and Siemens Healthcare and personal consulting fees not related to this paper from Progenity and Siemens Healthcare. These disclosures do not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Metz et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: The aim of the study is to evaluate whether values and the shape of the glucose curve during the oral glucose tolerance test (OGTT) in pregnancy identify women at risk of developing hypertension (HTN) later in life., Study Design: This category includes the secondary analysis of a follow-up from a mild gestational diabetes mellitus (GDM) study that included a treatment trial for mild GDM ( n  = 458) and an observational cohort of participants with abnormal 1-hour glucose loading test only (normal OGTT, n  = 430). Participants were assessed at a median of 7 (IQR 6-8) years after their index pregnancy, and trained staff measured their blood pressure (systolic blood pressure [SBP]; diastolic blood pressure [DBP]). The association between values and the shape of the glucose curve during OGTT in the index pregnancy and the primary outcome defined as elevated BP (SBP ≥120, DBP ≥80 mm Hg, or receiving anti-HTN medications), and secondary outcome defined as stage 1 or higher (SBP ≥130, DBP ≥80 mm Hg, or receiving anti-HTN medications) at follow-up were evaluated using multivariable regression, adjusting for maternal age, body mass index, and pregnancy-associated hypertension during the index pregnancy., Results: There was no association between fasting, 1-hour OGTT, and the outcomes. However, the 2-hour OGTT value was positively associated (adjusted odds ratio [aRR] per 10-unit increase 1.04, 95% CI 1.01-1.08), and the 3-hour was inversely associated (aRR per 10-unit increase 0.96, 95% CI 0.93-0.99) with the primary outcome. When the shape of the OGTT curve was evaluated, a monophasic OGTT response (peak at 1 hour followed by a decline in glucose) was associated with increased risk of elevated BP (41.3vs. 23.5%, aRR 1.66, 95% CI 1.17-2.35) and stage 1 HTN or higher (28.5 vs. 14.7%, aRR 1.83, 95% CI 1.15-2.92), compared with a biphasic OGTT response., Conclusion: Among persons with mild GDM or lesser degrees of glucose intolerance, the shape of the OGTT curve during pregnancy may help identify women who are at risk of HTN later in life, with biphasic shape to be associated with lower risk., Key Points: · The shape of the Oral Glucose Tolerance Test curve may help identify patients who are at risk of having elevated BP or HTN 5 to 10 years following pregnancy.. · The 2-hour Oral Glucose Tolerance Test values is positively associated with elevated BP 5 to 10 years following pregnancy.. · This supports the concept of pregnancy as a window to future health and represents a potential novel biomarker for maternal cardiovascular health screening.., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective: Umbilical artery Doppler (UAD) velocimetry abnormalities are associated with increased neonatal morbidity and mortality. Currently, there are no risk stratification methods to assist in antepartum management such as timing of antenatal corticosteroids (ACS). Therefore, we sought to develop a model to predict risk of delivery within 7 days following diagnosis of abnormal UAD velocimetry in patients with fetal growth restriction (FGR)., Study Design: Retrospective single referral center study of liveborn singleton pregnancies complicated by FGR and ≥1 abnormal UAD velocimetry value (≥95th percentile for gestational age [GA]). We considered 17 variables and used backward stepwise logistic regression to create a multivariable model for the prediction of delivery within 7 days. We assessed model fit with calibration, discrimination, likelihood ratios, and area under the curve. Internal validation of the model was assessed by using the bootstrap method., Results: Between 2008 and 2015, a total of 176 patients were eligible and included for model development. Median (range) GA at initial eligibility was 32.1 weeks (28.1-36.1 weeks) and from initial eligibility until delivery was 21 days (0-104 days). Fifty-two patients (30%) were delivered in the 7 days following inclusion. GA at first abnormal UAD, severity of first abnormal UAD, oligohydramnios, preeclampsia, and pre-pregnancy BMI were included in the model. The model had an area under the ROC curve of 0.94 (95% confidence interval [CI]: 0.90-0.98), sensitivity of 85%, and specificity of 91%. If the model alone were used for ACS timing, 85% of the cohort who delivered in the following week would have received ACS, and ACS would not have been given to 91% who delivered later. Internal validation yielded similar results with a mean area under the curve (95% CI) of 0.94 (0.88-0.98)., Conclusion: If validated externally, our model can be used to predict risk of delivery in patients with FGR and abnormal UAD velocimetry, potentially improving timing of ACS., Key Points: · Risk of delivery in seven days can be predicted.. · Risk of delivery can inform corticosteroid timing.. · External validation can further develop a clinical aid.., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: Hypertensive disorders of pregnancy are the leading cause of indicated preterm birth; however, the optimal delivery approach for pregnancies complicated by preterm hypertensive disorders of pregnancy remains uncertain., Objective: This study aimed to compare maternal and neonatal morbidity in patients with hypertensive disorders of pregnancy who either went induction of labor or prelabor cesarean delivery at <33 weeks' gestation. In addition, we aimed to quantify the length of induction of labor and rate of vaginal delivery in those who underwent induction of labor., Study Design: This is a secondary analysis of an observational study which included 115,502 patients in 25 hospitals in the United States from 2008 to 2011. Patients were included in the secondary analysis if they were delivered for pregnancy associated hypertension (gestational hypertension or preeclampsia) between 23 0 and <33 0 weeks' gestation; and were excluded for known fetal anomalies, multiple gestation, fetal malpresentation or demise, or a contraindication to labor. Maternal and neonatal adverse composite outcomes were evaluated by intended mode of delivery. Secondary outcomes were duration of labor induction and rate of cesarean delivery in those who underwent labor induction., Results: A total of 471 patients met inclusion criteria, of whom 271 (58%) underwent induction of labor and 200 (42%) underwent prelabor cesarean delivery. Composite maternal morbidity was 10.2% in the induction group and 21.1% in the cesarean delivery group (unadjusted odds ratio, 0.42 [0.25-0.72]; adjusted odds ratio, 0.44 [0.26-0.76]). Neonatal morbidity in the induction group vs the cesarean delivery was 51.9% and 63.8 %, respectively (unadjusted odds ratio, 0.61 [0.42-0.89]; adjusted odds ratio, 0.71 [0.48-1.06]). The frequency of vaginal delivery in the induction group was 53% (95% confidence interval, 46.8-58.7) and the median duration of labor was 13.9 hours (interquartile range, 8.7-22.2). The frequency of vaginal birth was higher in patients at or beyond 29 weeks (39.9% at 24 0 -28 6 weeks, 56.3% at 29 0 -<33 0 weeks; P=.01)., Conclusion: Among patients delivered for hypertensive disorders of pregnancy <33 0 weeks, labor induction compared with prelabor cesarean delivery is associated with significantly lower odds of maternal but not neonatal morbidity. More than half of patients induced delivered vaginally, with a median duration of labor induction of 13.9 hours., (Copyright © 2023 Elsevier Inc. All rights reserved.)

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.

Objective: This study aimed to evaluate maternal and neonatal outcomes by method of cervical ripening for labor induction among low-risk nulliparous individuals., Study Design: This is a secondary analysis of a multicenter randomized trial of labor induction at 39 weeks versus expectant management in low-risk nulliparous participants. Participants undergoing cervical ripening for labor induction in either group were included. Participants were excluded for preripening membrane rupture, abruption, chorioamnionitis, fetal demise, or cervical dilation ≥3.5 cm. Cervical ripening was defined by the initial method used: prostaglandin only (PGE; referent), Foley with concurrent prostaglandin (Foley-PGE), Foley only (Foley), and Foley with concurrent oxytocin (Foley-oxytocin). Coprimary outcomes were adverse maternal and neonatal composites. Secondary outcomes included cesarean delivery and length of labor and delivery (L&D) stay. Multivariable analysis was used to adjust for patient characteristics., Results: Of 6,106 participants included in the trial, 2,376 (38.9%) met criteria for this analysis. Of these, 1,247 (52.4%) had cervical ripening with PGE, 290 (12.2%) had Foley-PGE, 385 (16.2%) had Foley, and 454 (19.1%) had Foley-oxytocin. The maternal composite outcome was similar among participants who received Foley-PGE (24.1%, adjusted relative risk [aRR] = 1.21, 95% confidence interval [CI]: 0.96-1.52), Foley (21.3%, aRR = 1.16, 95% CI: 0.92-1.45), or Foley-oxytocin (19.4%, aRR = 1.04, 95% CI: 0.83-1.29), compared with PGE (19.7%). The neonatal composite outcome was less frequent in participants who received the Foley-PGE (2.4%, aRR = 0.35, 95% CI: 0.16-0.75) or Foley (3.6%, aRR = 0.51, 95% CI: 0.29-0.89) but did not reach statistical significance for participants who received Foley-oxytocin (4.6%, aRR = 0.63, 95% CI: 0.40-1.01) compared with PGE only (6.8%). Participants who received Foley-PGE or Foley-oxytocin had a shorter L&D stay (adjusted mean difference = -1.97 hours, 95% CI: -3.45 to -0.49 and -5.92 hours, 95% CI: -7.07 to -4.77, respectively), compared with PGE., Conclusion: In term low-risk nulliparous participants, Foley alone or concurrent with PGE is associated with a lower risk of adverse neonatal outcomes than with PGE alone. Length of L&D stay was the shortest with concurrent Foley-oxytocin., Key Points: · Adverse maternal outcomes are similar among different methods of cervical ripening in low-risk women.. · Adverse neonatal outcomes are less frequent with use of Foley alone or in combination with PGE.. · The use of Foley alone, or in combination with other agents, appears to be beneficial.., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective: To evaluate the association between maternal and delivery characteristics and self-reported perceived control during childbirth., Methods: A secondary analysis of a multicenter randomized trial was conducted to compare labor induction at 39 weeks of gestation with expectant management in low-risk nulliparous people. Six to 96 hours after delivery, participants who experienced labor completed the Labor Agentry Scale, a validated self-administered questionnaire to ascertain perceived control during childbirth. Scores range from 29 to 203, with higher scores indicating a sense of greater control. Multivariable linear regression was used to determine which maternal and delivery characteristics were associated with the Labor Agentry Scale score. Eligible characteristics included age, self-reported race and ethnicity, marital status, employment status, type of insurance, previous pregnancy loss before 20 weeks of gestation, body mass index (BMI), smoking, alcohol use, mode of delivery, labor pain (0-10 points), and a composite of perinatal death or severe neonatal complications. Significant variables ( P <.05) were retained in the final multivariable model, and adjusted mean differences (95% CIs) between groups were estimated., Results: Of 6,106 people enrolled in the trial, 6,038 experienced labor, of whom 5,750 (95.2%) completed the Labor Agentry Scale and were included in this analysis. Mean [95% CI] adjusted Labor Agentry Scale scores were significantly lower among those who identified as Asian (-6.4 [-10.5 to -2.3]) or Hispanic (-3.7 [-5.7 to -1.7]) compared with White, smoked compared with did not smoke (-2.8 [-5.5 to -0.1]), had BMIs of 35 or higher compared with less than 30 (-2.0 [-3.8 to -0.2]), were unemployed (-3.15 [-4.76 to -1.55]), did not have private health insurance (-2.61 [-4.47 to -0.76]), underwent operative vaginal (-5.1 [-7.7 to -2.6]) or cesarean (-14.4 [-16.1 to -12.6]) delivery compared with spontaneous vaginal delivery, and reported greater labor pain score of 8 or higher compared with less than 8 (-11.9 [-13.4 to -10.4]). Mean [95% CI] adjusted Labor Agentry Scale scores were significantly higher among people who were employed compared with unemployed (3.2 [1.6-4.8]) and had private compared with nonprivate insurance (2.6 [0.76-4.5])., Conclusion: In nulliparous people at low risk, unemployment, lack of private health insurance, Asian race, Hispanic ethnicity, smoking, operative delivery, and more labor pain were associated with lower perceived control during labor., Clinical Trial Registration: ClinicalTrials.gov , NCT01990612., Competing Interests: Financial Disclosure Alan T.N. Tita disclosed that money was paid to his institution from Pfizer. Geeta K. Swamy disclosed that she received payment from GlaxoSmithKline, Pfizer, and UpToDate. She has also been a consultant for Moderna. The other authors did not report any potential conflicts of interest., (Copyright © 2023 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Importance: SARS-CoV-2 infection can result in ongoing, relapsing, or new symptoms or other health effects after the acute phase of infection; termed post-acute sequelae of SARS-CoV-2 infection (PASC), or long COVID. The characteristics, prevalence, trajectory and mechanisms of PASC are ill-defined. The objectives of the Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC in Adults (RECOVER-Adult) are to: (1) characterize PASC prevalence; (2) characterize the symptoms, organ dysfunction, natural history, and distinct phenotypes of PASC; (3) identify demographic, social and clinical risk factors for PASC onset and recovery; and (4) define the biological mechanisms underlying PASC pathogenesis., Methods: RECOVER-Adult is a combined prospective/retrospective cohort currently planned to enroll 14,880 adults aged ≥18 years. Eligible participants either must meet WHO criteria for suspected, probable, or confirmed infection; or must have evidence of no prior infection. Recruitment occurs at 86 sites in 33 U.S. states, Washington, DC and Puerto Rico, via facility- and community-based outreach. Participants complete quarterly questionnaires about symptoms, social determinants, vaccination status, and interim SARS-CoV-2 infections. In addition, participants contribute biospecimens and undergo physical and laboratory examinations at approximately 0, 90 and 180 days from infection or negative test date, and yearly thereafter. Some participants undergo additional testing based on specific criteria or random sampling. Patient representatives provide input on all study processes. The primary study outcome is onset of PASC, measured by signs and symptoms. A paradigm for identifying PASC cases will be defined and updated using supervised and unsupervised learning approaches with cross-validation. Logistic regression and proportional hazards regression will be conducted to investigate associations between risk factors, onset, and resolution of PASC symptoms., Discussion: RECOVER-Adult is the first national, prospective, longitudinal cohort of PASC among US adults. Results of this study are intended to inform public health, spur clinical trials, and expand treatment options., Registration: NCT05172024., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Helen Chu reported consulting for Merck, GSK, Pfizer, Ellume, Janssen, Vindico CME, and the Bill and Melinda Gates Foundation, and receiving research support from Gates Ventures, Ellume, and Sanofi Pasteur. She also serves as a co-investigator on studies funded by Pfizer, Novavax, and GSK. Maged Costantine reported receiving grant support for work not related to RECOVER work/publications from Baxter International and Siemens Healthcare and personal consulting fees not related to this paper from Progenity, Quidel Ortho, and Siemens Healthcare. Kristine Erlandson reported research funding from Gilead Sciences and consulting payments from Gilead Sciences, Merck, and ViiV Pharmaceuticals, all paid to the University of Colorado. Emily Gallagher reported consulting for Novartis, Flare Therapeutics and Seagen. Edward Gardner reported research support (clinical trials) from Gilead Sciences, ViiV Healthcare, and Cepheid. Jason Goldman reported research support from Gilead, Eli Lilly and Regeneron; grants from Gilead, Merck (BARDA); personal fees for consulting from Gilead, Eli Lilly; and non-financial support from Adaptive Biotechnologies and Labcorp/Monogram Biosciences outside the submitted work. Timothy Heinrich reported grant support from Merck Inc. and consulting fees from Roche. Rachel Hess reported serving as Data Safety Monitoring Board member for Astellas Pharmaceuticals unrelated to the current work. Leora Horwitz reported being a member of the National Academy of Medicine Committee on the Long-Term Health Effects Stemming from COVID-19 and Implications for the Social Security Administration. Priscilla Hsue reported receiving honoraria from Gilead and Merck unrelated to study topic, receiving study drug from Regeneron unrelated to study topic, and receiving a research grant from Novartis. Judith James reported OMRF has licensed her IP to Progentec Biosciences, has received grant support from Progentec Biosciences, and serves on Advisory Committees to Glaxo Smith Klein, Merck and Novartis. Arthur Kim reports providing educational materials to Clinical Care Options and UpToDate and serving on a Data Safety Monitoring board for Kintor Pharmaceuticals, Ltd. Bruce Levy reported serving as a consultant for AstraZeneca, Entrinsic Biosciences, Gossamer Bio and Nocion Therapeutics and receiving research support from Amgen, Genentech, GlaxoSmithKline, Pieris Pharmaceuticals, SRA and Sanofi unrelated to the current work. Vincent Marconi reported receiving grants from NIH during the conduct of the study and grants from NIH, Veteran Affairs, and Centers for Disease Control and Prevention; grants, personal fees, nonfinancial support, and other from Lilly and Gilead; grants and personal fees from ViiV; and nonfinancial support from Bayer outside the submitted work. Grace McComsey reported serving as consultant for Merck, Gilead, ViiV, Janssen and have received research support from Pfizer, Vanda, Genentech, Roche, Redhill and Cognivue. Torri Metz reported being a site PI and a participant in the medical advisory board for the planning of a Pfizer clinical trial of SARS-CoV-2 vaccination in pregnancy. She also reported being a site PI for a Pfizer study evaluating the pharmacokinetics of Paxlovid in pregnant people with COVID-19. Janet Mullington reported support for investigator-initiated research by "Open Medicine Foundation and the Patient-Led Research Collaborative" Princess Ogbogu reported research support from Astrazeneca, GSK, Blueprint medical; advisory board for Astrazeneca, GSK, Sanofi, Kalvista; and consulting for Astrazeneca, GSK Sairam Parthasarathy reported research funding to Institution from Sergey Brin foundation of COVID and Long-COVID research. Michael Peluso reported consulting fees from Gilead Sciences and AstraZeneca, and service on data safety monitoring board for American Gene Technologies. Sean Quigley reported service on speaker Board for Servier, Alnylam, Agios; service on advisory board for Recordati, Alexion. Franz Rischard reported research support from NIH/NHLBI, United Therapeutics, Acceleron/Merck, Janssen, Insmed, Aerovate, and Bayer; and consulting/advisory compensation from Acceleron and Bayer. Nadine Rouphael reported being a consultant for ICON and EMMES as a safety consultant for clinical trials; service on the advisory boards for Moderna; funds to institution from Sanofi, Lilly, Merck, Quidel and Pfizer. PJ Utz reported stock ownership of Gilead and PI of biomarker studies for Pfizer STOP-PASC paxlovid trial Juan Wisnivesky received receiving consulting honorarium from Sanofi, Banook, Prospero, PPD and Atea and research grants from Sanofi, Regeneron, Axella, and Arnold Consultants., (Copyright: © 2023 Horwitz et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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.

Objective: To evaluate whether preterm birth rates changed in relation to the onset of the coronavirus disease 2019 (COVID-19) pandemic and whether any change depended on socioeconomic status., Methods: This is an observational cohort study of pregnant individuals with a singleton gestation who delivered in the years 2019 and 2020 at 1 of 16 U.S. hospitals of the Maternal-Fetal Medicine Units Network. The frequency of preterm birth for those who delivered before the onset of the COVID-19 pandemic (ie, in 2019) was compared with that of those who delivered after its onset (ie, in 2020). Interaction analyses were performed for people of different individual- and community-level socioeconomic characteristics (ie, race and ethnicity, insurance status, Social Vulnerability Index (SVI) of a person's residence)., Results: During 2019 and 2020, 18,526 individuals met inclusion criteria. The chance of preterm birth before the COVID-19 pandemic was similar to that after the onset of the pandemic (11.7% vs 12.5%, adjusted relative risk 0.94, 95% CI 0.86-1.03). In interaction analyses, race and ethnicity, insurance status, and the SVI did not modify the association between the epoch and the chance of preterm birth before 37 weeks of gestation (all interaction P >.05)., Conclusion: There was no statistically significant difference in preterm birth rates in relation to the COVID-19 pandemic onset. This lack of association was largely independent of socioeconomic indicators such as race and ethnicity, insurance status, or SVI of the residential community in which an individual lived., Competing Interests: Financial Disclosure: Torri D. Metz disclosed receiving payment from UpToDate (royalties for two topics on trial of labor after cesarean). Money was paid to her institution from Gestvision (site PI for preeclampsia point-of-care test; institution received money to conduct study [ended August 2020])and Pfizer (site PI for Phase III respiratory syncytial virus [RSV] vaccine trial, institution received money to conduct study). She is a member of medical advisory board for Pfizer and site PI for a COVID-19 vaccination trial in pregnancy Society for Maternal-Fetal Medicine Board of Directors (unpaid). Brenna L. Hughes disclosed receiving payment from Merck, UpToDate, and Johns Hopkins. The other authors did not report any potential conflicts of interest., (Copyright © 2023 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)