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Importance: The publication of the Antenatal Late Preterm Steroids (ALPS) trial in February 2016 demonstrated that antenatal administration of betamethasone in the late preterm period (between 34 to 36 weeks of gestation) for individuals with a high risk of delivery decreased neonatal respiratory morbidity. National estimates have suggested the trial did change obstetric practice, but little is known if the evidence was adopted uniformly or equitably., Objective: To assess regional variation in the use of late preterm steroids after the publication of the Antenatal Late Preterm Steroids (ALPS) Trial and to understand factors associated with a region's pace of adoption., Design, Setting, and Participants: This cross-sectional study used US natality data from February 2015 to October 2017 from hospital referral regions (HRRs) within the US. Inclusion criteria included live-born, nonanomalous, singleton, late preterm (34 to 36 completed weeks of gestation) neonates born to individuals without pregestational diabetes. This study was conducted from November 15, 2022, to January 13, 2023., Main Outcome and Measures: HRRs were categorized as either a slower adopter or faster adopter of antenatal late preterm steroids based on the observed vs expected pace of antenatal steroid adoption in a 1-year period after the trial's dissemination. Patient and regional factors hypothesized a priori to be associated with the uptake of late preterm steroids were compared between faster and slower adopters. Comparisons were made using Student t test or Wilcoxon rank-sum test, as appropriate. A multivariable logistic regression was constructed to identify factors associated with faster adopter status in the postperiod., Results: There were 666 097 late preterm births in 282 HRRs. The mean (SD) maternal age in HRRs was 27.9 (1.2) years. The median (IQR) percentage of births by race categories in HRRs for patients identifying as American Indian or Alaskan Native was 0.5% (0.2%-1.3%); Asian or Pacific Islander, 3.0% (1.7%-5.3%); Black, 12.9% (5.1%-29.1%); and White, 78.6% (66.6%-87.0%). The median percentage of births in HRRs to patients of Hispanic ethnicity was 11.2% (6.3%-27.4%). In this study, 136 HRRs (48.2%) were classified as faster adopters and 146 (51.8%) were classified as slower adopters. Faster adopters increased their steroid use by 12.1 percentage points (from 5.9% to 18.0%) compared with a 5.5 percentage point increase (from 3.7% to 9.2%) among slower adopters (P < .001). Most examined patient and regional factors were not associated with a region's pace of adoption, with the exception of the regional prevalence of prior preterm birth (adjusted odds ratio [aOR], 2.04 [95% CI, 1.48-2.82]) and the percentage of deliveries at 34 to 35 weeks of gestation (aOR, 0.68 [95% CI, 0.47-0.99]) compared with 36 weeks., Conclusions and Relevance: In this cross-sectional study, there was widespread geographic variation in the adoption of antenatal steroid administration for late preterm births that largely remained unexplained by population factors. These findings should prompt further investigations to barriers to timely or equitable access to new evidence-based practices and guide future dissemination strategies with the goal of more uniform adoption.

Importance: Prior studies using large registries have suggested a modest increase in risk for neurodevelopmental diagnoses among children of mothers with immune activation during pregnancy, and such risk may be sex-specific., Objective: To determine whether in utero exposure to SARS-CoV-2 is associated with sex-specific risk for neurodevelopmental disorders up to 18 months after birth, compared with unexposed offspring born during or prior to the COVID-19 pandemic period., Design, Setting, and Participants: This retrospective cohort study included the live offspring of all mothers who delivered between January 1 and December 31, 2018 (born and followed up before the COVID-19 pandemic), between March 1 and December 31, 2019 (born before and followed up during the COVID-19 pandemic), and between March 1, 2020, and May 31, 2021 (born and followed up during the COVID-19 pandemic). Offspring were born at any of 8 hospitals across 2 health systems in Massachusetts., Exposures: Polymerase chain reaction evidence of maternal SARS-CoV-2 infection during pregnancy., Main Outcomes and Measures: Electronic health record documentation of International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnostic codes corresponding to neurodevelopmental disorders., Results: The COVID-19 pandemic cohort included 18 355 live births (9399 boys [51.2%]), including 883 (4.8%) with maternal SARS-CoV-2 positivity during pregnancy. The cohort included 1809 Asian individuals (9.9%), 1635 Black individuals (8.9%), 12 718 White individuals (69.3%), and 1714 individuals (9.3%) who were of other race (American Indian or Alaska Native, Native Hawaiian or other Pacific Islander, more than 1 race); 2617 individuals (14.3%) were of Hispanic ethnicity. Mean maternal age was 33.0 (IQR, 30.0-36.0) years. In adjusted regression models accounting for race, ethnicity, insurance status, hospital type (academic center vs community), maternal age, and preterm status, maternal SARS-CoV-2 positivity was associated with a statistically significant elevation in risk for neurodevelopmental diagnoses at 12 months among male offspring (adjusted OR, 1.94 [95% CI 1.12-3.17]; P = .01) but not female offspring (adjusted OR, 0.89 [95% CI, 0.39-1.76]; P = .77). Similar effects were identified using matched analyses in lieu of regression. At 18 months, more modest effects were observed in male offspring (adjusted OR, 1.42 [95% CI, 0.92-2.11]; P = .10)., Conclusions and Relevance: In this cohort study of offspring with SARS-CoV-2 exposure in utero, such exposure was associated with greater magnitude of risk for neurodevelopmental diagnoses among male offspring at 12 months following birth. As with prior studies of maternal infection, substantially larger cohorts and longer follow-up will be required to reliably estimate or refute risk.

Importance: Risk-stratification tools are routinely used in obstetrics to assist care teams in assessing and communicating risk associated with delivery. Electronic health record data and machine learning methods may offer a novel opportunity to improve and automate risk assessment., Objective: To compare the predictive performance of natural language processing (NLP) of clinician documentation with that of a previously validated tool to identify individuals at high risk for maternal morbidity., Design, Setting, and Participants: This retrospective diagnostic study was conducted at Brigham and Women's Hospital and Massachusetts General Hospital, Boston, Massachusetts, and included individuals admitted for delivery at the former institution from July 1, 2016, to February 29, 2020. A subset of these encounters (admissions from February to December 2018) was part of a previous prospective validation study of the Obstetric Comorbidity Index (OB-CMI), a comorbidity-weighted score to stratify risk of severe maternal morbidity (SMM)., Exposures: Natural language processing of clinician documentation and OB-CMI scores., Main Outcomes and Measures: Natural language processing of clinician-authored admission notes was used to predict SMM in individuals delivering at the same institution but not included in the prospective OB-CMI study. The NLP model was then compared with the OB-CMI in the subset with a known OB-CMI score. Model discrimination between the 2 approaches was compared using the DeLong test. Sensitivity and positive predictive value for the identification of individuals at highest risk were prioritized as the characteristics of interest., Results: This study included 19 794 individuals; 4034 (20.4%) were included in the original prospective validation study of the OB-CMI (testing set), and the remaining 15 760 (79.6%) composed the training set. Mean (SD) age was 32.3 (5.2) years in the testing cohort and 32.2 (5.2) years in the training cohort. A total of 115 individuals in the testing cohort (2.9%) and 468 in the training cohort (3.0%) experienced SMM. The NLP model was built from a pruned vocabulary of 2783 unique words that occurred within the 15 760 admission notes from individuals in the training set. The area under the receiver operating characteristic curve of the NLP-based model for the prediction of SMM was 0.76 (95% CI, 0.72-0.81) and was comparable with that of the OB-CMI model (0.74; 95% CI, 0.70-0.79) in the testing set (P = .53). Sensitivity (NLP, 28.7%; OB-CMI, 24.4%) and positive predictive value (NLP, 19.4%; OB-CMI, 17.6%) were comparable between the NLP and OB-CMI high-risk designations for the prediction of SMM., Conclusions and Relevance: In this study, the NLP method and a validated risk-stratification tool had a similar ability to identify patients at high risk of SMM. Future prospective research is needed to validate the NLP approach in clinical practice and determine whether it could augment or replace tools requiring manual user input.

Importance: Epidemiologic studies suggest maternal immune activation during pregnancy may be associated with neurodevelopmental effects in offspring., Objective: To evaluate whether in utero exposure to SARS-CoV-2 is associated with risk for neurodevelopmental disorders in the first 12 months after birth., Design, Setting, and Participants: This retrospective cohort study examined live offspring of all mothers who delivered between March and September 2020 at any of 6 Massachusetts hospitals across 2 health systems. Statistical analysis was performed from October to December 2021., Exposures: Maternal SARS-CoV-2 infection confirmed by a polymerase chain reaction test during pregnancy., Main Outcomes and Measures: Neurodevelopmental disorders determined from International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) diagnostic codes over the first 12 months of life; sociodemographic and clinical features of mothers and offspring; all drawn from the electronic health record., Results: The cohort included 7772 live births (7466 pregnancies, 96% singleton, 222 births to SARS-CoV-2 positive mothers), with mean (SD) maternal age of 32.9 (5.0) years; offspring were 9.9% Asian (772), 8.4% Black (656), and 69.0% White (5363); 15.1% (1134) were of Hispanic ethnicity. Preterm delivery was more likely among exposed mothers: 14.4% (32) vs 8.7% (654) (P = .003). Maternal SARS-CoV-2 positivity during pregnancy was associated with greater rate of neurodevelopmental diagnoses in unadjusted models (odds ratio [OR], 2.17 [95% CI, 1.24-3.79]; P = .006) as well as those adjusted for race, ethnicity, insurance status, offspring sex, maternal age, and preterm status (adjusted OR, 1.86 [95% CI, 1.03-3.36]; P = .04). Third-trimester infection was associated with effects of larger magnitude (adjusted OR, 2.34 [95% CI, 1.23-4.44]; P = .01)., Conclusions and Relevance: This cohort study of SARS-CoV-2 exposure in utero found preliminary evidence that maternal SARS-CoV-2 may be associated with neurodevelopmental sequelae in some offspring. Prospective studies with longer follow-up duration will be required to exclude confounding and confirm these associations.

Importance: The Antenatal Late Preterm Steroids (ALPS) trial demonstrated a 20% reduction in the risk of respiratory complications in neonates at risk for a late-preterm birth who were exposed to antenatal corticosteroids compared with those who were not., Objective: To assess whether new evidence of steroid administration for neonatal respiratory benefit in the late-preterm period is associated with changes in obstetric practice and the use of assisted ventilation for the neonate after delivery., Design, Setting, and Participants: This cross-sectional study of US births from February 1, 2015, to October 31, 2017, as ascertained from US natality data, included live-born, singleton neonates born between 34 and 36 completed weeks of gestation to people without pregestational diabetes. An interrupted time series analysis using Poisson regression models was conducted. Data were analyzed from July 11, 2022, to November 9, 2022., Exposures: Public dissemination of the ALPS trial results, which occurred during a 9-month period from February 1, 2016 (first published online), to October 31, 2016 (time of the last major professional society's guideline update in the months after the trial's publication)., Main Outcomes and Measures: Steroid use, any assisted ventilation use, and assisted ventilation use for more than 6 hours immediately after the dissemination period., Results: A total of 707 862 births were included, divided among the 12-month predissemination period (n = 250 643), dissemination period (n = 195 736), and 12-month postdissemination period (n = 261 493). Most births were at 36 weeks of gestation (53.9% in the predissemination and postdissemination period; P = .10). Small but significant differences were found between the predissemination and postdissemination period cohorts: there were more individuals 35 years or older (19.5% vs 17.9%), fewer White individuals (67.8% vs 69.8%), and more publicly insured individuals (50.5% vs 50.1%) in the postdissemination period compared with the predissemination period, respectively (P < .001 for all). Compared with what rates were expected based on the predissemination trends, the adjusted rate of steroid use increased from 5.0% to 11.7% (adjusted incidence rate ratio [IRR], 2.34; 95% CI, 2.13-2.57), and assisted ventilation use decreased from 8.9% to 8.2% (adjusted IRR, 0.91; 95% CI, 0.85-0.98) after the dissemination period. No change was observed in assisted ventilation use for more than 6 hours (adjusted IRR, 0.98; 95% CI, 0.87-1.10)., Conclusions and Relevance: These findings suggest that there was an immediate change in practice of administering antenatal steroids and a reduction in neonatal morbidity among late-preterm births associated with the dissemination of the ALPS trial, suggesting that this evidence may be translating into a reduction in immediate respiratory morbidity outside the context of a clinical trial.

Importance: Biological data are lacking with respect to risk of vertical transmission and mechanisms of fetoplacental protection in maternal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection., Objective: To quantify SARS-CoV-2 viral load in maternal and neonatal biofluids, transplacental passage of anti-SARS-CoV-2 antibody, and incidence of fetoplacental infection., Design, Setting, and Participants: This cohort study was conducted among pregnant women presenting for care at 3 tertiary care centers in Boston, Massachusetts. Women with reverse transcription-polymerase chain reaction (RT-PCR) results positive for SARS-CoV-2 were recruited from April 2 to June 13, 2020, and follow-up occurred through July 10, 2020. Contemporaneous participants without SARS-CoV-2 infection were enrolled as a convenience sample from pregnant women with RT-PCR results negative for SARS-CoV-2., Exposures: SARS-CoV-2 infection in pregnancy, defined by nasopharyngeal swab RT-PCR., Main Outcomes and Measures: The main outcomes were SARS-CoV-2 viral load in maternal plasma or respiratory fluids and umbilical cord plasma, quantification of anti-SARS-CoV-2 antibodies in maternal and cord plasma, and presence of SARS-CoV-2 RNA in the placenta., Results: Among 127 pregnant women enrolled, 64 with RT-PCR results positive for SARS-CoV-2 (mean [SD] age, 31.6 [5.6] years) and 63 with RT-PCR results negative for SARS-CoV-2 (mean [SD] age, 33.9 [5.4] years) provided samples for analysis. Of women with SARS-CoV-2 infection, 23 (36%) were asymptomatic, 22 (34%) had mild disease, 7 (11%) had moderate disease, 10 (16%) had severe disease, and 2 (3%) had critical disease. In viral load analyses among 107 women, there was no detectable viremia in maternal or cord blood and no evidence of vertical transmission. Among 77 neonates tested in whom SARS-CoV-2 antibodies were quantified in cord blood, 1 had detectable immunoglobuilin M to nucleocapsid. Among 88 placentas tested, SARS-CoV-2 RNA was not detected in any. In antibody analyses among 37 women with SARS-CoV-2 infection, anti-receptor binding domain immunoglobin G was detected in 24 women (65%) and anti-nucleocapsid was detected in 26 women (70%). Mother-to-neonate transfer of anti-SARS-CoV-2 antibodies was significantly lower than transfer of anti-influenza hemagglutinin A antibodies (mean [SD] cord-to-maternal ratio: anti-receptor binding domain immunoglobin G, 0.72 [0.57]; anti-nucleocapsid, 0.74 [0.44]; anti-influenza, 1.44 [0.80]; P < .001). Nonoverlapping placental expression of SARS-CoV-2 receptors angiotensin-converting enzyme 2 and transmembrane serine protease 2 was noted., Conclusions and Relevance: In this cohort study, there was no evidence of placental infection or definitive vertical transmission of SARS-CoV-2. Transplacental transfer of anti-SARS-CoV-2 antibodies was inefficient. Lack of viremia and reduced coexpression and colocalization of placental angiotensin-converting enzyme 2 and transmembrane serine protease 2 may serve as protective mechanisms against vertical transmission.

Importance: Unexpected complications in term newborns have been recently adopted by the Joint Commission as a marker of obstetric care quality., Objective: To understand the variation and patient and hospital factors associated with severe unexpected complications in term neonates among hospitals in the United States., Design, Setting, and Participants: This cross-sectional study collected data from all births in US counties with 1 obstetric hospital using county-identified birth certificate data and American Hospital Association annual survey data from January 1, 2015, through December 31, 2017. All live-born, term, singleton infants weighing at least 2500 g were included. The data analysis was performed from December 1, 2018, through June 30, 2019., Exposures: Severe unexpected newborn complication, defined as neonatal death, 5-minute Apgar score of 3 or less, seizure, use of assisted ventilation for at least 6 hours, or transfer to another facility., Main Outcomes and Measures: Between-hospital variation and patient and hospital factors associated with unexpected newborn complications., Results: A total of 1 754 852 births from 576 hospitals were included in the analysis. A wide range of hospital complication rates was found (range, 0.6-89.9 per 1000 births; median, 15.3 per 1000 births [interquartile range, 9.6-22.0 per 1000 births]). Hospitals with high newborn complication rates were more likely to care for younger, white, less educated, and publicly insured women with more medical comorbidities compared with hospitals with low complication rates. In the adjusted models, there was little effect of case mix to explain the observed between-county variation (11.3%; 95% CI, 10.0%-12.6%). Neonatal transfer was the primary factor associated with complication rates, especially among hospitals with the highest rates (66.0% of all complications). The risk for unexpected neonatal complication increased by more than 50% for those neonates born at hospitals without a neonatal intensive care unit compared with those with a neonatal intensive care unit (adjusted odds ratio, 1.55; 95% CI, 1.38-1.75)., Conclusions and Relevance: In this study, severe unexpected complication rates among term newborns varied widely. When included in the metric numerator, neonatal transfer was the primary factor associated with complications, especially among hospitals with the highest rates. Transfers were more likely to be necessary when infants were born in hospitals with lower levels of neonatal care. Thus, if this metric is to be used in its current form, it would appear that accreditors, regulatory bodies, and payers should consider adjusting for or stratifying by a hospital's level of neonatal care to avoid disincentivizing against appropriate transfers.