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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.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.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.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).Steroid use, any assisted ventilation use, and assisted ventilation use for more than 6 hours immediately after the dissemination period.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).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.

Objective The aim of this study was to determine if a universally applied risk score threshold for severe maternal morbidity (SMM) resulted in different performance characteristics among subgroups of the population. Study Design This is a retrospective cohort study of deliveries that occurred between July 1, 2016, and June 30, 2020, in a single health system. We examined the performance of a validated comorbidity score to stratify SMM risk in our cohort. We considered the risk score that was associated with the highest decile of predicted risk as a “screen positive” for morbidity. We then used this same threshold to calculate the sensitivity and positive predictive value (PPV) of this “highest risk” designation among subgroups of the overall cohort based on the following characteristics: age, race/ethnicity, parity, gestational age, and planned mode of delivery. Results In the overall cohort of 53,982 women, the C-statistic was 0.755 (95% confidence interval [CI], 0.741–0.769) and calibration plot demonstrated that the risk score was well calibrated. The model performed less well in the following groups: non-White or Hispanic (C-statistic, 0.734; 95% CI, 0.712–0.755), nulliparas (C-statistic, 0.735; 95% CI, 0.716–0.754), term deliveries (C-statistic, 0.712; 95% CI, 0.694–0.729), and planned vaginal delivery (C-statistic, 0.728; 95% CI, 0.709–0.747). There were differences in the PPVs by gestational age (7.8% term and 29.7% preterm) and by planned mode of delivery (8.7% vaginal and 17.7% cesarean delivery). Sensitivities were lower in women who were Conclusion The performance of a risk score for SMM can vary by population subgroups when using standard thresholds derived from the overall cohort. If applied without such considerations, such thresholds may be less likely to identify certain subgroups of the population that may be at increased risk of SMM. Key Points

OBJECTIVE To examine the association between county-level caesarean delivery (CD) rates among women at low risk and morbidity among term newborns. DESIGN Cross-sectional study. SETTING Population-based study of US county-level birth data from 2015 to 2017. POPULATION Nulliparous women with term, singleton, vertex-presenting infants (NTSV) at low risk for morbidity. METHODS The primary exposure was county-level CD rates. MAIN OUTCOME MEASURES The outcome was morbidity among the low-risk NTSV cohort, categorised as severe (5-minute Apgar score of ≤3, assisted ventilation for ≥6 hours, severe neurologic injury or seizure, transfer or death) or moderate (5-minute Apgar score of 3, administration of antibiotics or assisted ventilation at delivery). We used linear regression models to determine the association between county NTSV CD and neonatal morbidity rates with cluster robust standard errors. RESULTS The analysis included data from 2 753 522 births in 952 counties from all 48 states. The mean NTSV CD rate was 23.6% (standard deviation 4.8%). The median severe and moderate neonatal morbidity rates were 15.2 (interquartile range, IQR 9.4-23.6) and 52.5 (IQR 33.4-75.7) per 1000 births, respectively. In the unadjusted analysis using the risk-adjusted exposure and outcome, every percentage point increase in the CD rate of a county was associated with 0.6 (95% CI -0.9, -0.3) and 2.3 fewer (95% CI -3.4, -1.1) cases of severe and moderate neonatal morbidity per 1000 live births. After adjustment for other county factors, the relationships remained significant. These findings were tested in multiple sensitivity analyses. CONCLUSIONS Lower county-level NTSV CD rates were associated with a small increase in morbidity among term newborns in the USA. TWEETABLE ABSTRACT Lower county-level caesarean delivery rates were associated with an increase in morbidity among term newborns in the USA.

ImportancePrior studies using large registries 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.ObjectiveTo determine whether in utero exposure to the novel coronavirus SARS-CoV-2 is associated with sex-specific risk for neurodevelopmental disorders up to 18 months after birth, compared to unexposed offspring born during or prior to the pandemic period.DesignRetrospective cohort.ParticipantsLive offspring of all mothers who delivered between March 2018 and May 2021 at any of eight hospitals across two health systems in Massachusetts.ExposurePCR evidence of maternal SARS-CoV-2 infection during pregnancy.Main Outcome and MeasuresElectronic health record documentation of ICD-10 diagnostic codes corresponding to neurodevelopmental disorders.ResultsThe pandemic cohort included 18,323 live births, including 877 (4.8%) to individuals with SARS-CoV-2 positivity during pregnancy. The cohort included 1806 (9.9%) Asian individuals, 1634 (8.9%) Black individuals, 1711 (9.3%) individuals of another race, and 12,694 (69%) White individuals; 2614 (14%) were of Hispanic ethnicity. Mean maternal age was 33.0 years (IQR 30.0-36.0). In adjusted regression models accounting for race, ethnicity, insurance status, hospital type (academic center vs. community), maternal age, and preterm status, SARS-CoV-2 positivity was associated with statistically significant elevation in risk for neurodevelopmental diagnoses among male offspring (adjusted OR 1.99, 95% CI 1.19-3.34; p=0.009) but not female offspring (adjusted OR 0.90, 95% CI 0.43-1.88; p=0.8). Similar effects were identified using matched analyses in lieu of regression.Conclusion and RelevanceSARS-CoV-2 exposure in utero was associated with greater magnitude of risk for neurodevelopmental diagnoses among male offspring in the 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.Trial RegistrationNAKey PointsQuestionAre rates of neurodevelopmental disorder diagnoses greater among male or female children with COVID-19 exposure in utero compared to those with no such exposure?FindingsIn a cohort of 18,323 infants delivered after February 2020, males but not females born to mothers with a positive SARS-CoV-2 PCR test during pregnancy were more likely to receive a neurodevelopmental diagnosis in the first 12 months after delivery, even after accounting for preterm delivery.MeaningThese findings suggest that male offspring exposed to COVID-19 in utero may be at increased risk for neurodevelopmental disorders.

ImportanceRisk-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.ObjectiveTo 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 ParticipantsThis 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).ExposuresNatural language processing of clinician documentation and OB-CMI scores.Main Outcomes and MeasuresNatural 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.ResultsThis 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 RelevanceIn 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.

Background Expression of angiotensin-converting enzyme 2 (ACE2) and type II transmembrane serine protease (TMPRSS2), host molecules required for viral entry, may underlie sex differences in vulnerability to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We investigated whether placental ACE2 and TMPRSS2 expression vary by fetal sex in the presence of maternal SARS-CoV-2 infection. Methods Placental ACE2 and TMPRSS2 expression was quantified by quantitative reverse transcription polymerase chain reaction (RT-PCR) and by Western blot in 68 pregnant women (38 SARS-CoV-2 positive, 30 SARS-CoV-2 negative) delivering at Mass General Brigham from April to June 2020. The impact of fetal sex and maternal SARS-CoV-2 exposure on ACE2 and TMPRSS2 was analyzed by 2-way analysis of variance (ANOVA). Results Maternal SARS-CoV-2 infection impacted placental TMPRSS2 expression in a sexually dimorphic fashion (2-way ANOVA interaction, P = .002). We observed no impact of fetal sex or maternal SARS-CoV-2 status on ACE2. TMPRSS2 expression was significantly correlated with ACE2 expression in males (Spearman ρ = 0.54, P = .02) but not females (ρ = 0.23, P = .34) exposed to maternal SARS-CoV-2. Conclusions Sex differences in placental TMPRSS2 but not ACE2 were observed in the setting of maternal SARS-CoV-2 infection, which may have implications for offspring vulnerability to placental infection.

Epidemiologic studies suggest maternal immune activation during pregnancy may be associated with neurodevelopmental effects in offspring.To evaluate whether in utero exposure to SARS-CoV-2 is associated with risk for neurodevelopmental disorders in the first 12 months after birth.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.Maternal SARS-CoV-2 infection confirmed by a polymerase chain reaction test during pregnancy.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.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).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.

We sought to develop a prediction model using prenatal diagnosis codes that could help clinicians objectively stratify a women’s risk for delivery-related morbidity. We performed a prospective cohort study of women delivering at a single academic medical center between 2016 and 2019. Diagnosis codes from outpatient encounters were extracted from the electronic health record. Standard and common machine-learning methods for variable selection were compared. The performance characteristics from the selected model in the training data set—a LASSO model with a lambda that minimized the Bayes information criteria—were compared in a testing and external validation set. The model identified a group of women, those in the highest decile of predicted risk, who were at a two to threefold increased risk of maternal morbidity. As EHR data becomes more ubiquitous, other data types generated from the prenatal period may improve the model’s performance.

The aim of the study is to determine the relationship between a hospital's provision of subspecialty neonatal and maternal care. Specifically, we sought to understand where women with high-risk maternal conditions received intrapartum care and estimate the potential transfer burden for those with maternal high-risk conditions delivering at hospitals without subspecialty maternal care. This is a descriptive study using data from 2015 State Inpatient Databases and the American Hospital Association Annual Survey. Characteristics were compared between hospitals based on the concordance of their maternal and neonatal care. The incidences of high-risk maternal conditions (pre-eclampsia with severe features, placenta previa with prior cesarean delivery, cardiac disease, pulmonary edema, and acute liver failure) were compared. To determine the potential referral burden, the percent of women with high-risk conditions delivering at a hospital without subspecialty maternal care but delivering in a county with a hospital with subspecialty maternal care was calculated. The analysis included 486,398 women who delivered at 544 hospitals, of which 104 (19%) and 182 (33%) had subspecialty maternal and neonatal care, respectively. Ninety-eight hospitals provided both subspecialty maternal and neonatal care; however, 84 hospitals provided only subspecialty neonatal care but no subspecialty maternal care. Among high-risk maternal conditions examined, approximately 65% of women delivered at a hospital with subspecialty maternal care. Of the remainder who delivered at a hospital without subspecialty maternal care, one-third were in a county where subspecialty care was present. For women with high-risk conditions who delivered in a county without subspecialty maternal care, the median distance to the closest county with subspecialty care was 52.8 miles (IQR 34.3-87.7 miles). Approximately 50% of hospitals with subspecialty neonatal care do not provide subspecialty maternal care. This discordance may present a challenge when both high-risk maternal and neonatal conditions are present.· High-risk women who deliver at hospitals without subspecialty care are in more rural areas.. · Approximately 50% of hospitals with subspecialty neonatal care do not provide subspecialty maternal care.. · This discordance may present a challenge when both high-risk maternal and neonatal conditions are present..

Although childbirth-related posttraumatic stress (CB-PTSD) has received recognition, how sexual assault (SA) history influences obstetrical and traumatic stress outcomes remains unclear. Six hundred eighty-three women provided information about their childbirth and mental health. Obstetric complications and unplanned cesareans were more prevalent among women with SA history. They also had higher rates of probable CB-PTSD and were two times more likely to have premature deliveries than women without SA history. Screening women for history of sexual trauma is warranted to optimize birth outcomes.

ImportancePrior 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.ObjectiveTo 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 ParticipantsThis 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.ExposuresPolymerase chain reaction evidence of maternal SARS-CoV-2 infection during pregnancy.Main Outcomes and MeasuresElectronic health record documentation of International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnostic codes corresponding to neurodevelopmental disorders.ResultsThe 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 RelevanceIn 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.

OBJECTIVE To estimate the incidence of failed induction of labor and the associated patient risk factors. METHODS We performed a case-control study from a cohort of nulliparous women who delivered between 39 and 41 weeks of gestation after an induction of labor in one of seven hospitals. Cases of failed induction were defined using the Obstetric Care Consensus criteria (ie, cesarean delivery performed in early labor [less than 6 cm dilatation] after at least 12 hours of oxytocin administration from membrane rupture). For each case of failed induction, the next four women who did not meet the criteria for failed induction of labor were selected for the control group, matched by hospital. We identified characteristics associated with failed induction of labor using a multivariable conditional logistic regression that was constructed with backward stepwise method for variable selection. RESULTS Across the hospitals, 4,123 of 10,175 nulliparous women were induced (40.5%), of whom 82 had a failed induction of labor (2.0%). A total of 328 women were selected for the matched control group. Baseline characteristics were similar between the groups. Compared with women in the control group, women with a failed induction were more likely to have a delivery body mass index (BMI) of 40 or higher (28.0 vs 8.2%, P

High-dose nitric oxide is a novel treatment associated with improved oxygenation and decreased tachypnea in pregnant patients with severe coronavirus disease 2019 (COVID-19)., BACKGROUND: Rescue therapies to treat or prevent progression of coronavirus disease 2019 (COVID-19) hypoxic respiratory failure in pregnant patients are lacking. METHOD: To treat pregnant patients meeting criteria for severe or critical COVID-19 with high-dose (160–200 ppm) nitric oxide by mask twice daily and report on their clinical response. EXPERIENCE: Six pregnant patients were admitted with severe or critical COVID-19 at Massachusetts General Hospital from April to June 2020 and received inhalational nitric oxide therapy. All patients tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. A total of 39 treatments was administered. An improvement in cardiopulmonary function was observed after commencing nitric oxide gas, as evidenced by an increase in systemic oxygenation in each administration session among those with evidence of baseline hypoxemia and reduction of tachypnea in all patients in each session. Three patients delivered a total of four neonates during hospitalization. At 28-day follow-up, all three patients were home and their newborns were in good condition. Three of the six patients remain pregnant after hospital discharge. Five patients had two negative test results on nasopharyngeal swab for SARS-CoV-2 within 28 days from admission. CONCLUSION: Nitric oxide at 160–200 ppm is easy to use, appears to be well tolerated, and might be of benefit in pregnant patients with COVID-19 with hypoxic respiratory failure.

Objective To characterize the obstetric outcomes and placental pathology in live births arising from vanishing twin pregnancies compared with nonreduced in vitro fertilization (IVF) pregnancies. Methods This is a retrospective cohort study of live births resulting from fresh embryo transfers after IVF cycles with autologous oocytes from 2004 through 2017 at a large academic fertility center. Clinical information and pathology reports were reviewed. Placental diagnoses were coded using established nosology by expert placental pathologists. Analysis of variance, Kruskal-Wallis, Pearson's χ, and Fisher exact tests were used, as appropriate, to compare pathology categories between pregnancy outcomes. Mixed effects logistic regression models were generated to reveal the association between pregnancy outcome and placenta pathology, controlling for pregnancies arising in the same woman and various suspected confounders. Results Of 905 fresh autologous IVF cycles with placental pathology available for review, we identified 73 vanishing twin pregnancies (8.1%), 556 singleton pregnancies (61.4%), and 276 twin pregnancies (30.5%). Vanishing twin syndrome was not associated with preterm delivery, route of delivery, growth restriction or other obstetric outcomes as compared with IVF singleton pregnancies. However, vanishing twin syndrome pregnancies showed distinctive placental pathologies including an increased rate of small placentas (less than the 10th percentile by weight), with more anatomical abnormalities than IVF singleton pregnancies (odds ratio 1.73, 95% CI 0.94-3.19; adjusted odds ratio 2.15, 95% CI 1.08-4.28). The frequency of placental vascular and inflammatory pathologies associated with IVF vanishing twin syndrome pregnancies were similar to that of IVF singleton pregnancies. Loss of a twin after 8 weeks of gestation was not associated with greater risks of placental pathologies. Conclusion In vitro fertilization pregnancies affected by vanishing twin syndrome did not have significant differences in obstetric or perinatal outcomes as compared with twin or singleton gestations. However, early twin loss was potentially associated with differences in placental development associated with a higher rate of small placentas and other anatomic pathologies.

The COVID-19 pandemic disrupted access to routine in-person prenatal care, potentially leading to higher risk of out-of-hospital deliveries. Unplanned out-of-hospital deliveries pose a substantial risk of morbidity and mortality for pregnant patients and newborns. Our objective was to determine the change in rate of emergency medical services (EMS)-attended out-of-hospital deliveries during the COVID-19 pandemic. We hypothesized that COVID-19-related stay-at-home orders were associated with a higher rate of out-of-hospital deliveries during the initial wave of COVID-19. We conducted an interrupted time series analysis using the 2019 and 2020 National EMS Information System datasets. We included 9-1-1 scene activations for patients 12-50 years old with out-of-hospital deliveries who were treated and transported by EMS. We calculated the weekly rate of deliveries per 100,000 EMS emergency activations each year overall, and for each census division. The interruption modeled was the enactment of stay-at-home orders, with March 25-31 selected as when most orders had been enacted. We fit ordinary least squares regression models with Newey-West standard errors to adjust for autocorrelation, testing for a change in level and slope overall and by census division. A total of 10,778 out-of-hospital deliveries were included, 58% (n = 6,254) in 2020. The mean weekly rate of out-of-hospital deliveries in 2019 was 29.4 per 100,000 activations (95% CI: 28.4 to 30.4) versus 33.0 (95% CI: 31.8 to 34.1) in 2020. There was an immediate increase of 6.3 deliveries per 100,000 activations (95% CI: 3.3 to 9.3) after the week of March 25-31, with a subsequent decrease of 0.3 deliveries per 100,000 per week after (95% CI: −0.4 to −0.2). There were also statistically significant immediate increases in out-of-hospital deliveries after March 25-31 in the New England, East North Central, West South Central, and Mountain divisions. EMS-attended out-of-hospital deliveries remained rare during the COVID-19 pandemic, but there was an immediate increase during the initial wave of the pandemic with evidence of geographic variation. Large-scale disruptions in the health care system may result in increases in uncommon patient presentations to EMS.

ObjectiveTo assess knowledge and confidence in COVID-19 vaccine counseling among practitioners who provide care to pregnant persons and to describe factors associated with confidence in counseling.Study DesignA web-based anonymous survey was distributed via email to a cross-sectional convenience sample of OB/GYN, Primary Care, and Internal Medicine faculty at three hospitals in a single healthcare network in Massachusetts. Individual demographics and institution-specific variables were included in the survey along with questions assessing both attitudes toward COVID-19 illness in pregnancy as well as confidence in counseling regarding the use of the vaccine for pregnant patients.ResultsAlmost all providers (151, 98.1%) reported already receiving or being scheduled to receive a COVID-19 vaccine, and a majority of providers (111, 72.1%) reported that they believe the benefits of the mRNA COVID-19 vaccine in pregnancy outweigh the risks. Forty-one (26.6%) reported feeling very confident in counseling patients who primarily speak English about the evidence for mRNA vaccination in pregnancy, and 36 (23%) reported feeling very confident in counseling patients who are not primarily English-speaking. Forty-three providers (28.1%) expressed strong confidence in their comfort talking to individuals with vaccine hesitancy based on historic and continued racism and systemic injustices. The sources that survey respondents most commonly used to find information regarding COVID-19 vaccination in pregnancy were the CDC (112, 74.2%), hospital-specific resources (94, 62.3%) and ACOG (82, 54.3%).ConclusionWhile providers reported high personal uptake of COVID-19 vaccination and felt that the benefits of vaccination outweigh the risks in pregnancy, less than one-third felt very confident in counseling pregnant patients about available evidence for mRNA vaccine safety in pregnancy. Ensuring that providers feel comfortable bridging the gap between their belief that the vaccine is beneficial for pregnant patients and their comfort with holding conversations with patients regarding vaccination is paramount in order to ensure equitable access to vaccines for pregnant patients.

ImportanceEpidemiologic studies suggest maternal immune activation during pregnancy may be associated with neurodevelopmental effects in offspring.ObjectiveTo determine whether in utero exposure to the novel coronavirus SARS-CoV-2 is associated with risk for neurodevelopmental disorders in the first 12 months after birth.DesignRetrospective cohortParticipantsLive offspring of all mothers who delivered between March and September 2020 at one of six Massachusetts hospitals across two health systems.ExposureSARS-CoV-2 infection confirmed by PCR during pregnancyMain Outcome and MeasuresNeurodevelopmental disorders determined from ICD-10 diagnostic codes over 12 months; sociodemographic and clinical features of mothers and offspring; all drawn from the electronic health record.ResultsThe cohort included 7,772 live births (7,466 pregnancies, 96% singleton, 222 births to SARS-CoV-2 positive mothers), with mean maternal age of 32.9 years; offspring were 9.9% Asian, 8.4% Black, and 69.0% white; 15.1% were of Hispanic ethnicity. Preterm delivery was more likely among exposed mothers (14% versus 8.7%; p=.003). Maternal SARS-CoV-2 positivity during pregnancy was associated with greater rate of neurodevelopmental diagnoses (crude OR 2.17 [95% CI 1.24-3.79, p=0.006]) as well as models adjusted for race, ethnicity, insurance status, offspring sex, maternal age, and preterm status (adjusted OR 1.86 [95% CI 1.03-3.36, p=0.04]). Third-trimester infection was associated with effects of larger magnitude (adjusted OR 2.34, 95% CI 1.23-4.44, p=0.01)Conclusion and RelevanceOur results provide 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 effects.Trial RegistrationNAKey PointsQuestionDoes COVID-19 exposure in utero increase the risk for neurodevelopmental disorders in the first year of life?FindingsIn a cohort of babies delivered during COVID-19, those born to mothers with a positive SARS-CoV-2 PCR test during pregnancy were more likely to receive a neurodevelopmental diagnosis in the first 12 months after delivery, even after accounting for preterm delivery.MeaningThese preliminary findings suggest that COVID-19 exposure may impact neurodevelopment, and highlight the need for prospective investigation of outcomes in children exposed to COVID-19 in utero.

Knowledge of childbirth outcomes of Black and Latinx individuals during the coronavirus pandemic is limited. Black/African American and Latinx/Hispanic individuals were matched to non-Hispanic white individuals on socio-demographics. Minority individuals were nearly three times more likely to have clinically significant traumatic stress in response to childbirth and two times more likely to report postpartum depression. Unplanned Cesarean rates were higher and incidences of skin-to-skin and breastfeeding were lower in the minority group. Racial and ethnic maternal disparities exist during COVID-19.

This cross-sectional study evaluates the association between dissemination of the Antenatal Late Preterm Steroid trial and changes in steroid exposure among term newborns.

Severe maternal morbidity and mortality remain public health priorities in the United States, given their high rates relative to other high-income countries and the notable racial and ethnic disparities that exist. In general, accurate risk stratification methods are needed to help patients, providers, hospitals, and health systems plan for and potentially avert adverse outcomes.Our objective was to understand if machine learning methods with natural language processing of history and physical notes could identify a group of patients at high risk of maternal morbidity on admission for delivery without relying on any additional patient information (eg, demographics and diagnosis codes).This was a retrospective study of people admitted for delivery at 2 hospitals (hospitals A and B) in a single healthcare system between July 1, 2016, and June 30, 2020. The primary outcome was severe maternal morbidity, as defined by the Centers for Disease Control and Prevention; furthermore, we examined nontransfusion severe maternal morbidity. Clinician documents designated as history and physical notes were extracted from the electronic health record for processing and analysis. A bag-of-words approach was used for this natural language processing analysis (ie, each history or physical note was converted into a matrix of counts of individual words (or phrases) that occurred within the document). The least absolute shrinkage and selection operator models were used to generate prediction probabilities for severe maternal morbidity and nontransfusion severe maternal morbidity for each note. Model discrimination was assessed via the area under the receiver operating curve. Discrimination was compared between models using the DeLong test. Calibration plots were generated to assess model calibration. Moreover, the natural language processing models with history and physical note texts were compared with validated obstetrical comorbidity risk scores based on diagnosis codes.There were 13,572 delivery encounters with history and physical notes from hospital A, split between training (AIn this practical application of machine learning, we demonstrated the capabilities of natural language processing for the prediction of severe maternal morbidity based on provider documentation inherently generated at the time of admission. This work should serve as a catalyst for providers, hospitals, and electronic health record systems to explore ways that artificial intelligence can be incorporated into clinical practice and evaluated rigorously for their ability to improve health.

Background Postpartum depression (PPD) is a common condition associated with childbirth, yet many women do not receive the treatment they need. Despite the growing practice of PPD screening, treatment and clinical outcomes among patients identified as likely having PPD remain unclear. Method Women who were systematically screened and scored ≥12 on the Edinburgh Postnatal Depression Scale (EPDS)-indicative of possible PPD-at their routine 6-week postpartum visit were eligible to participate and were contacted after 3 months for a follow-up interview and assessment. Results A total of 33 women participated in the study, out of 100 who scored ≥12 on the EPDS. Among the participants, 70% reported they received a referral to a health care provider for PPD, and nearly one-half said that they received psychotherapy and/or were prescribed a psychotropic. The 2 most commonly described barriers to treatment were perceptions of not needing or wanting help and concerns about breastfeeding while taking psychotropics. Nearly 40% of women scored ≥12 on the EPDS at the follow-up interview. Conclusions Further systematic research on outcomes after PPD screening is needed to ensure that screening translates into meaningfully improved clinical outcomes.

There is a persistent bias toward higher prevalence and increased severity of coronavirus disease 2019 (COVID-19) in males. Underlying mechanisms accounting for this sex difference remain incompletely understood. Interferon responses have been implicated as a modulator of COVID-19 disease in adults and play a key role in the placental antiviral response. Moreover, the interferon response has been shown to alter Fc receptor expression and therefore may affect placental antibody transfer. Here, we examined the intersection of maternal-fetal antibody transfer, viral-induced placental interferon responses, and fetal sex in pregnant women infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Placental Fc receptor abundance, interferon-stimulated gene (ISG) expression, and SARS-CoV-2 antibody transfer were interrogated in 68 human pregnancies. Sexually dimorphic expression of placental Fc receptors, ISGs and proteins, and interleukin-10 was observed after maternal SARS-CoV-2 infection, with up-regulation of these features in placental tissue of pregnant individuals with male fetuses. Reduced maternal SARS-CoV-2–specific antibody titers and impaired placental antibody transfer were also observed in pregnancies with a male fetus. These results demonstrate fetal sex-specific maternal and placental adaptive and innate immune responses to SARS-CoV-2.

Routine postpartum care is essential for managing pregnancy complications, like hypertension and diabetes, or screening for new conditions, such as depression. Insurance coverage can impact women's ability to access these postpartum services, with women who change or lose insurance postpartum having a lower likelihood of receiving the recommended postpartum care. Pregnancy-related Medicaid eligibility is only federally guaranteed for a minimum of 60 days after birth, creating the potential for publicly insured women to lose their insurance and their access to postpartum care.The objective of this study was to examine the rates of postpartum readmission and predictors of uninsurance at readmission before and after 60 days postpartum for Medicaid vs privately paid births.This was a retrospective cohort study in which data from the 2017 Nationwide Readmissions Database were used. Women who delivered with Medicaid or private insurance between January 2017 and June 2017 were included. Potential readmissions that were identified between 0 and 180 days after their childbirth hospitalization were included. The primary outcomes of interest were postpartum readmission and delivery payer at postpartum readmission, evaluated at 30-day intervals up to 180 days postpartum. Multivariable logistic regressions were used to determine the association of the risk for readmission and the risk for being uninsured at the time of readmission with insurance provider at the time of delivery. The analysis was also conducted for a subset of acute-cause readmissions or those not likely to be related to chronic or preexisting medical conditions.A total of 24,719 (2.7%) patients were readmitted within 180 days after delivery: 14,179 (54.1%) had Medicaid delivery insurance and 10,540 (40.2%) had private insurance at delivery. Readmission rates decreased over the time intervals after delivery for both delivery payer types, but were consistently higher for those with Medicaid. The rate of uninsurance at readmission increased more with each postpartum month for those with Medicaid than for those with private insurance at delivery: from 0.9% (95% confidence interval, 0.7-1.1) at 0 to 30 days to 9.7% (95% confidence interval, 8.1-11.6) at 150 to 180 days postpartum for those with Medicaid and from 0.2% (95% confidence interval, 0.1-0.4) at 0 to 30 days to 2.6% (95% confidence interval, 1.6-4.1) at 150 to 180 days postpartum for those with private insurance. Medicaid coverage at the time of delivery was a significant predictor of being readmitted (adjusted odds ratio, 1.86; 95% confidence interval, 1.75-1.97) and uninsured at the time of readmission (adjusted odds ratio, 3.99; 95% confidence interval, 2.88-5.52) when compared with being privately insured. Findings were similar for the acute-cause readmissions.Women with Medicaid at delivery have a higher risk for readmission and uninsurance at readmission than privately insured women beyond 60 days postpartum. This analysis provides further evidence of the insurance instability women face in the postpartum period, especially by those insured by Medicaid at the time of delivery, and should promote discussions among policymakers, payers, and providers on strategies to ensure coverage and access to care for women and their families after childbirth. For states considering to expand their eligibility criteria to 1 year postpartum, this study provides evidence on the vulnerabilities and unique risks that women with Medicaid face after 60 days postpartum.

Obstetrical providers have had to rapidly rethink how to provide comprehensive prenatal care during the SARS-CoV-2 pandemic. At our institution, we implemented a risk-stratified approach to incorporating telemedicine into our prenatal care. The objective of this study was to determine acceptability of virtual prenatal care and preferences for future pregnancies among our patient population.We sought feedback from a convenience sample of patients regarding the acceptability of virtual prenatal care and desires for future pregnancies.We found that virtual prenatal care is acceptable to patients, and the majority would like to incorporate it into future post-pandemic pregnancy care, although preferences differ by race.Virtual prenatal care should continue to be employed in post-pandemic obstetric practice. Obstetrical providers must determine how to incorporate this practice in a risk-stratified and equitable fashion.

BACKGROUND Although there are many indications for a cesarean delivery, the “optimal” cesarean delivery rate is unknown. Neonatal and maternal morbidity have largely not been considered in the generation of hospital-level cesarean delivery rate targets. OBJECTIVE We sought to examine if the widely adopted and reported markers of maternal and neonatal morbidity were associated with hospital cesarean delivery rates to provide context for potential comparison and consideration for defining cesarean delivery rate targets. We hypothesized that hospitals with higher cesarean delivery rates would have increased rates of severe maternal morbidity, though we were less certain of the associations of the cesarean delivery rates with unexpected newborn complications. STUDY DESIGN This is a cross-sectional, ecological study using data from the 2016 Nationwide Readmission Database of hospitals with at least 100 deliveries per year. The exposure of interest was hospital cesarean delivery rate. The outcomes were (1) severe maternal morbidity with and without transfusion—in accordance with the Centers for Disease Control and Prevention's definition, and (2) neonatal morbidity—defined using The Joint Commission's Perinatal Quality metric of moderate and severe unexpected newborn complications among term, singleton, and nonanomalous neonates. Before assuming a single linear relationship to model the associations between morbidity and cesarean delivery rates, the Joinpoint Regression Analysis program was used to examine for potential splines in the relationships with both severe maternal morbidity (with and without transfusion) and severe and moderate unexpected newborn complications. Poisson regression model was then used to determine the association between morbidity and cesarean delivery rates. RESULTS The analysis included 831,111 deliveries from 621 hospitals. The mean cesarean delivery rate was 30.5%. The median severe maternal morbidity rate was 1.40 per 100 deliveries (interquartile range, 0.71–2.21 per 1000 deliveries). Excluding transfusion, the median severe maternal morbidity rate was 0.47 per 100 deliveries (interquartile range, 0.22–0.73 per 100 deliveries). The median rate of severe and moderate unexpected newborn complications was 1.01 per 100 low-risk newborns (interquartile range, 0.64–1.69 per 100 low-risk newborns) and 1.79 per 1000 low-risk newborns (interquartile range, 0.94–2.93 per 100 low-risk newborns), respectively. In the unadjusted analysis, every percentage point increase in a hospital's cesarean delivery rate was associated with a 3.4% (95% confidence interval, 2.3%–4.4%) and a 2.3% (95% confidence interval, 1.0%–3.5%) increase in severe maternal morbidity including and excluding transfusion, respectively. After adjustment for the case mix and hospital factors, only the relationship with severe maternal morbidity including transfusion remained significant: 3.3% (95% confidence interval, 1.7%–4.9%) increase in severe maternal morbidity per 1 percentage point increase in the cesarean delivery rate. There was no observed association between cesarean delivery rates and unexpected newborn complications CONCLUSION Severe maternal morbidity and unexpected newborn complications occur in fewer than 5 in 100 births. Findings from this analysis of hospitals with cesarean delivery rates ranging from 6.8%–56.3% suggest that those with lower cesarean delivery rates have lower severe maternal morbidity (which includes transfusion) and similar unexpected newborn complications compared with hospitals with higher cesarean delivery rates. This work may provide a helpful context to providers, hospitals, and policymakers who are measuring and reporting outcomes. Regarding neonatal morbidity in particular, the Joint Commission manual notes that the unexpected newborn complication metric was specifically designed to be compared against maternal-focused metrics such as cesarean delivery rates. More work is needed to define and identify appropriate measures of maternal and neonatal morbidity for these types of comparisons.

Objective To identify the association of the Affordable Care Act's Medicaid expansion with payment for delivery, early access to prenatal care, preterm birth, and birth weights considered small for gestational age (SGA). Methods A difference-in-difference design was used to assess changes in outcomes before and after Medicaid expansion in expansion states, using nonexpansion states as a control group. We used national birth certificate data from 2009 to 2017. Difference-in-difference linear probability models were used to assess the effects of the policy implementation, adjusting for demographics, month of birth, state, year, and county-level unemployment rates. Standard errors were clustered at the state level. Two prespecified subgroup analyses were performed of nulliparous women and women with no more than a high school diploma. Results The study sample included 8,701,889 women from 15 expansion states and 9,509,994 from 11 nonexpansion states. In the adjusted analysis, the percentage of Medicaid-covered deliveries increased by 2.3 absolute percentage points (95% CI 0.2-4.4, P=.04) in expansion states compared with nonexpansion states. There were no significant changes in the proportion of women who were uninsured, as there was a relative decrease in the percentage of deliveries covered by private insurance (-2.8 percentage points [95% CI -4.9 to -0.8, P=.01]). There were also no significant differences in the rate of women initiating prenatal care in the first trimester, preterm birth rates, or rates of low birth weight after the Medicaid expansion. Findings were similar in both subgroups. Conclusion Medicaid expansion was associated with increased Medicaid coverage for childbirth in expansion states; similar gains in private coverage were seen in nonexpansion states. There were no associations with changes in early access to prenatal care, preterm birth, or SGA birth weights.

Objective This study was aimed to determine if admission-to-delivery times vary between term nulliparous women with prelabor rupture of membranes (PROM) who initially receive oxytocin compared with buccal misoprostol for labor induction. Study Design This is a retrospective cohort of 130 term, nulliparous women with PROM and cervical dilation of ≤2 cm who underwent induction of labor with intravenous oxytocin or buccal misoprostol. The primary outcome was time from admission to delivery. Linear regressions with log transformation were used to estimate the effect of induction agent on time to delivery. Results Women receiving oxytocin had faster admission-to-delivery times than women receiving misoprostol (16.9 vs. 19.9 hours, p = 0.013). There were no significant differences in secondary outcomes between the groups. In the adjusted model, women who received misoprostol had a 22% longer time from admission to delivery (95% CI 5.0–42.0%) compared with women receiving oxytocin. Conclusion In term nulliparous patients with PROM, intravenous oxytocin is associated with faster admission-to-delivery times than buccal misoprostol.

Background: The decrease in trial of labor after cesarean (TOLAC) at institutions that offer this option suggests that patient preference could be a factor in the declining TOLAC rate. However, data regarding how women value the potential processes and outcomes of TOLAC and elective repeat cesarean delivery (ERCD) are limited. We sought to determine how women view the processes and outcomes of TOLAC and ERCD and identify sociodemographic and clinical factors associated with these preferences. Materials and Methods: This is a multicenter cross-sectional study of mode of delivery preferences among TOLAC-eligible women at 26–34 weeks gestation. The time tradeoff metric was used to obtain utilities for the processes and outcomes of TOLAC and ERCD. Multivariable regression analysis was utilized to identify independent predictors of utilities. Results: The 299 study participants constituted a geographically and racially/ethnically diverse group. Although uncomplicated TOLAC resulting in vaginal birth after cesarean and uncomplicated ERCD resulted in high utility values, any alteration in either the process or outcome resulted in substantial utility decrements. In multivariable regression analysis, race/ethnicity, insurance status, and order of scenario presentation emerged as statistically significant predictors. Conclusions: Information regarding both maternal and infant implications is important to women in discussions about approach to delivery. Both the way in which information regarding labor interventions and potential complications is presented and the characteristics of the women contemplating this information affect its impact. These findings underscore the need for evidence-based decision support to help create realistic expectations and incorporate informed patient preferences into decision-making to optimize both clinical outcomes and individual patient experience for women with a prior cesarean delivery.

The primary objective was to determine the association between preconception insurance and initiation of prenatal care. This retrospective cohort uses data from the Pregnancy Risk Assessment Monitoring System (2009–2013). Self-reported preconception insurance status was the primary exposure. The primary outcome was first trimester initiation of prenatal care. Secondary outcomes included: preterm delivery, birth weight, and the presence of birth defects. Survey-weighted generalized linear models were used to calculate risk ratios and accounted for state-level clustering. Of the 181,675 included women from 32 states, 21.1% were uninsured prior to conception. 88% of insured women vs. 70% of uninsured women initiated care in the first trimester. Uninsured women were less likely to initiate care in the first trimester (adjusted relative risk (RR) 0.87 (95% confidence interval 0.85–0.89), p

To estimate the effects of the Affordable Care Act Medicaid expansion provision that was largely implemented in 2014 on preconception insurance coverage among low-income women.We used a quasiexperimental, difference-in-difference design to compare changes in preconception insurance coverage among low-income women living in expansion compared with nonexpansion states before and after the Medicaid expansions. Women with family incomes 138% the federal poverty level or less who participated in the Pregnancy Risk Assessment Monitoring System from 2009 to 2015 from states that did or did not expand their Medicaid programs on January 1, 2014, were included. The exposure of interest was the state Medicaid expansion. The primary outcome was insurance status 1 month before conception. We conducted additional subgroup and sensitivity analyses to test the assumptions of the model and the robustness of the findings.The study sample included 30,495 women from eight states that expanded Medicaid under the Affordable Care Act and 26,561 patients from seven states in that did not. The rate of preconception Medicaid coverage was 30.8% prepolicy and 35.6% postpolicy in nonexpansion states and 43.2% prepolicy and 56.8% postpolicy in expansion states. There was a significantly greater increase in Medicaid coverage in expansion states after the policy implementation (adjusted difference-in-difference estimate +8.6% points, 95% CI 1.1-16.0). Rates of preconception uninsurance were 44.2% prepolicy and 34.3% postpolicy in nonexpansion states and 37.4% prepolicy and 23.5% postpolicy in expansion states. There was no significant difference in the changes in uninsurance between the two groups in the postpolicy period (adjusted difference-in-difference estimate -4.1, 95% CI -11.1 to 2.9). Non-Medicaid insurance coverage was 25.3% prepolicy and 30.5% postpolicy in nonexpansion states and 19.4% prepolicy and 19.7% postpolicy in expansion states. Relative to nonexpansion states, there was a significant decrease in non-Medicaid coverage in the expansion states in the postpolicy period (adjusted difference-in-difference estimate -4.7, 95% CI -8.3 to -1.1). The results were robust to alternate model specifications and study period definitions.Medicaid expansion was associated with increased enrollment in Medicaid before pregnancy among low-income women; however, there were no changes in the rates of uninsurance. Additional years of postpolicy data are needed to fully assess the effects of the policy change.

There is a persistent bias toward higher prevalence and increased severity of coronavirus disease 2019 (COVID-19) in males. Underlying mechanisms accounting for this sex difference remain incompletely understood. Interferon responses have been implicated as a modulator of COVID-19 disease in adults and play a key role in the placental antiviral response. Moreover, the interferon response has been shown to alter Fc receptor expression and therefore may affect placental antibody transfer. Here, we examined the intersection of maternal-fetal antibody transfer, viral-induced placental interferon responses, and fetal sex in pregnant women infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Placental Fc receptor abundance, interferon-stimulated gene (ISG) expression, and SARS-CoV-2 antibody transfer were interrogated in 68 human pregnancies. Sexually dimorphic expression of placental Fc receptors, ISGs and proteins, and interleukin-10 was observed after maternal SARS-CoV-2 infection, with up-regulation of these features in placental tissue of pregnant individuals with male fetuses. Reduced maternal SARS-CoV-2–specific antibody titers and impaired placental antibody transfer were also observed in pregnancies with a male fetus. These results demonstrate fetal sex-specific maternal and placental adaptive and innate immune responses to SARS-CoV-2.

BackgroundSex differences in vulnerability to and severity of SARS-CoV-2 infection have been described in non-pregnant populations. ACE2 and TMPRSS2, host molecules required for viral entry, are regulated by sex steroids and expressed in the placenta. We sought to investigate whether placental ACE2 and TMPRSS2 expression vary by fetal sex and in the presence of maternal SARS-CoV-2 infection.MethodsPlacental ACE2 and TMPRSS2 were quantified in 68 pregnant individuals (38 SARS-CoV-2 positive, 30 SARS-CoV-2 negative) delivering at Mass General Brigham from April to June 2020. Maternal SARS-CoV-2 status was determined by nasopharyngeal RT-PCR. Placental SARS-CoV-2 viral load was quantified. RTqPCR was performed to quantify expression of ACE2 and TMPRSS2 relative to the reference gene YWHAZ. Western blots were performed on placental homogenates to quantify protein levels. The impact of fetal sex and SARS-CoV-2 exposure on ACE2 and TMPRSS2 expression was analyzed by 2-way ANOVA.ResultsSARS-CoV-2 virus was undetectable in all placentas. Maternal SARS-CoV-2 infection impacted TMPRSS2 placental gene and protein expression in a sexually dimorphic fashion (2-way ANOVA interaction p-value: 0.002). We observed no impact of fetal sex or maternal SARS-CoV-2 status on placental ACE2 gene or protein expression. Placental TMPRSS2 expression was significantly correlated with ACE2 expression in males (Spearman’s ρ=0.54, p=0.02) but not females (ρ=0.23, p=0.34) exposed to maternal SARS-CoV-2.ConclusionsSex differences in placental TMPRSS2 but not ACE2 were observed in the setting of maternal SARS-CoV-2 infection. These findings may have implications for offspring vulnerability to placental infection and vertical transmission.These findings may have implications for offspring vulnerability to placental infection and vertical transmission.

Background Prehospital obstetric events encountered by emergency medical services (EMS) can be high-risk patient presentations for which suboptimal care can cause substantial morbidity and mortality. The frequency of prehospital obstetric events is unclear because existing descriptions have reported obstetric and gynecological conditions together, without delineating specific patient presentations. Our objective was to identify the types, frequency, and acuity of prehospital obstetric events treated by EMS personnel in the US. Methods We conducted a cross-sectional analysis of EMS patient care records in the 2018 National EMS Information System dataset (n=22,532,890). We focused on EMS activations (i.e., calls for service) for an emergency scene response for patients aged 12-50 years with evidence of an obstetric event. Type of obstetric event was determined by examining patient symptoms, the treating EMS provider’s impression (i.e., field diagnosis), and procedures performed. High patient acuity was ascertained by EMS documentation of patient status and application of the modified early obstetric warning system (MEOWS) criteria, with concordance assessed using Cohen’s kappa. Descriptive statistics were calculated to describe the primary symptoms, impressions, and frequency of each type of obstetric event among these activations. Results A total of 107,771 (0.6%) of EMS emergency activations were identified as involving an obstetric event. The most common presentation was early or threatened labor (15%). Abdominal complaints, including pain and other digestive/abdomen signs and symptoms, was the most common primary symptom (29%) and primary impression (18%). We identified 3,489 (3%) out-of-hospital deliveries, of which 1,504 were preterm. Overall, EMS providers documented 34% of patients as being high acuity, similar to the MEOWS criteria (35%); however, there were high rates of missing data for EMS documented acuity (19%), poor concordance between the two measures (Cohen’s kappa=0.12), and acuity differences for specific conditions (e.g., high acuity of non-cephalic presentations, 77% in EMS documentation versus 53% identified by MEOWS). Conclusion Prehospital obstetric events were infrequently encountered by EMS personnel, and about one-third were high acuity. Additional work to understand the epidemiology and clinical care of these patients by EMS would help to optimize prehospital care and outcomes.