Compromised SARS-CoV-2-specific placental antibody transfer.

SARS-CoV-2 infection causes more severe disease in pregnant women compared to age-matched non-pregnant women. Whether maternal infection causes changes in the transfer of immunity to infants remains unclear. Maternal infections have previously been associated with compromised placental antibody transfer, but the mechanism underlying this compromised transfer is not established. Here, we used systems serology to characterize the Fc profile of influenza-, pertussis-, and SARS-CoV-2-specific antibodies transferred across the placenta. Influenza- and pertussis-specific antibodies were actively transferred. However, SARS-CoV-2-specific antibody transfer was significantly reduced compared to influenza- and pertussis-specific antibodies, and cord titers and functional activity were lower than in maternal plasma. This effect was only observed in third-trimester infection. SARS-CoV-2-specific transfer was linked to altered SARS-CoV-2-antibody glycosylation profiles and was partially rescued by infection-induced increases in IgG and increased FCGR3A placental expression. These results point to unexpected compensatory mechanisms to boost immunity in neonates, providing insights for maternal vaccine design.

The simultaneous occurrence of gestational diabetes and hypertensive disorders of pregnancy affects fetal growth and neonatal morbidity.

BACKGROUND: Gestational diabetes is associated with increased risk of hypertensive disorders of pregnancy, but there are limited data on fetal growth and neonatal outcomes when both conditions are present. OBJECTIVE: We evaluated the risk of abnormal fetal growth and neonatal morbidity in pregnancies with co-occurrence of gestational diabetes and hypertensive disorders of pregnancy. STUDY DESIGN: In a retrospective study of 47,093 singleton pregnancies, we compared the incidence of appropriate for gestational age birthweight in pregnancies affected by gestational diabetes alone, hypertensive disorders of pregnancy alone, or both gestational diabetes and hypertensive disorders of pregnancy with that in pregnancies affected by neither disorder using generalized estimating equations (covariates: maternal age, nulliparity, body mass index, insurance type, race, marital status, and prenatal care site). Secondary outcomes were large for gestational age birthweight, small for gestational age birthweight, and a neonatal morbidity composite outcome (stillbirth, hypoglycemia, hyperbilirubinemia, respiratory distress, encephalopathy, preterm delivery, neonatal death, and neonatal intensive care unit admission). RESULTS: The median (interquartile range) birthweight percentile in pregnancies with both gestational diabetes and hypertensive disorders of pregnancy (50 [24.0-78.0]; N=179) was similar to that of unaffected pregnancies (50 [27.0-73.0]; N=35,833). However, the absolute rate of appropriate for gestational age birthweight was lower for gestational diabetes/hypertensive disorders of pregnancy co-occurrence (78.2% vs 84.9% for unaffected pregnancies). Adjusted analyses showed decreased odds of appropriate for gestational age birthweight in pregnancies with both gestational diabetes and hypertensive disorders of pregnancy compared with unaffected pregnancies (adjusted odds ratio, 0.72 [95% confidence interval, 0.52-1.00]; P=.049), and in pregnancies complicated by gestational diabetes alone (adjusted odds ratio, 0.78 [0.68-0.89]; P<.001) or hypertensive disorders of pregnancy alone (adjusted odds ratio, 0.73 [0.66-0.81]; P<.001). The absolute risk of large for gestational age birthweight was greater in pregnancies with both gestational diabetes and hypertensive disorders of pregnancy (14.5%) than in unaffected pregnancies (8.2%), without apparent difference in the risk of small for gestational age birthweight (7.3% vs 6.9%). However, in adjusted models comparing pregnancies with gestational diabetes/hypertensive disorders of pregnancy co-occurrence with unaffected pregnancies, neither an association with large for gestational age birthweight (adjusted odds ratio, 1.33 [0.88-2.00]; P=.171) nor small for gestational age birthweight (adjusted odds ratio, 1.32 [0.80-2.19]; P=.293) reached statistical significance. Gestational diabetes/hypertensive disorders of pregnancy co-occurrence carried an increased risk of neonatal morbidity that was greater than that observed with either condition alone (gestational diabetes/hypertensive disorders of pregnancy: adjusted odds ratio, 3.13 [2.35-4.17]; P<.001; gestational diabetes alone: adjusted odds ratio, 2.01 [1.78-2.27]; P<.001; hypertensive disorders of pregnancy alone: adjusted odds ratio, 1.38 [1.26-1.50]; P<.001). CONCLUSION: Although pregnancies with both gestational diabetes and hypertensive disorders of pregnancy have a similar median birthweight percentile to those affected by neither condition, pregnancies concurrently affected by both conditions have a higher risk of abnormal fetal growth and neonatal morbidity.

Performance of a Maternal Risk Stratification System for Predicting Low Apgar Scores.

OBJECTIVE: Maternal risk stratification systems are increasingly employed in predicting and preventing obstetric complications. These systems focus primarily on maternal morbidity, and few tools exist to stratify neonatal risk. We sought to determine if a maternal risk stratification score was associated with neonatal morbidity. STUDY DESIGN: Retrospective cohort study of patients with liveborn infants born at ≥24 weeks at four hospitals in one health system between January 1, 2020, and December 31, 2020. The Expanded Obstetric Comorbidity Score (EOCS) is used as the maternal risk score. The primary neonatal outcome was 5-minute Apgar <7. Logistic regression models determined associations between EOCS and neonatal morbidity. Secondary analyses were performed, including stratifying outcomes by gestational age and limiting analysis to "low-risk" term singletons. Model discrimination assessed using the area under the receiver operating characteristic curves (AUC) and calibration via calibration plots. RESULTS: A total of 14,497 maternal-neonatal pairs were included; 236 (1.6%) had 5-minute Apgar <7; EOCS was higher in 5-minute Apgar <7 group (median 41 vs. 11, p < 0.001). AUC for EOCS in predicting Apgar <7 was 0.72 (95% Confidence Interval (CI) 0.68, 0.75), demonstrating relatively good discrimination. Calibration plot revealed that those in the highest EOCS decile had higher risk of neonatal morbidity (7.6 vs. 1.7%, p < 0.001). When stratified by gestational age, discrimination weakened with advancing gestational age: AUC 0.70 for <28 weeks, 0.63 for 28 to 31 weeks, 0.64 for 32 to 36 weeks, and 0.61 for ≥37 weeks. When limited to term low-risk singletons, EOCS had lower discrimination for predicting neonatal morbidity and was not well calibrated. CONCLUSION: A maternal morbidity risk stratification system does not perform well in most patients giving birth, at low risk for neonatal complications. The findings suggest that the association between EOCS and 5-minute Apgar <7 likely reflects a relationship with prematurity. This study cautions against intentional or unintentional extrapolation of maternal morbidity risk for neonatal risk, especially for term deliveries. KEY POINTS: · EOCS had moderate discrimination for Apgar <7.. · Predictive performance declined when limited to low-risk term singletons.. · Relationship between EOCS and Apgar <7 was likely driven by prematurity..

Multilevel barriers and facilitators to widespread use of preconception carrier screening in the United States.

PURPOSE: Although preconception reproductive genetic carrier screening (RGCS) is preferred to screening during pregnancy, population-wide preconception screening is not routinely performed in the United States. We explored the multilevel barriers to the widespread adoption of preconception RGCS in the United States via key informant interviews. METHODS: Semi-structured virtual video interviews were conducted with 29 informants with a breadth of professional expertise between May and October 2022. Data collection and qualitative analyses were guided by the Consolidated Framework for Implementation Research and socioecological model. Analysis focused on identifying barriers to delivering preconception RGCS at and across different levels of health care and exploring potential facilitators of preconception RGCS delivery. RESULTS: Barriers to preconception RGCS were identified at the levels of test characteristics, patients and couples, clinicians and care teams, and the external health care and policy environments. Across the different levels of care delivery, 3 themes of barriers emerged: (1) fragmentation and inconsistencies hinder care delivery, (2) gaps in knowledge, misconceptions, and uncertainties about RGCS are pervasive, and (3) expanding preconception RGCS in the diverse US population presents unique implementation challenges. Potential solutions were detailed by informants. CONCLUSION: Identifying individual and thematic barriers to preconception RGCS delivery may help to define strategies to alleviate obstacles.

Cost-effectiveness of induction of labor at 39 weeks vs expectant management by cervical examination.

BACKGROUND: Previous analyses have demonstrated the cost effectiveness of elective induction of labor at 39 weeks of gestation for healthy nulliparous people. However, elective induction of labor is resource intensive, and optimal resource allocation requires a thorough understanding of which subgroups of patients will benefit most. OBJECTIVE: This study aimed to determine whether induction of labor at 39 weeks of gestation is more cost-effective in patients with favorable or unfavorable cervical examinations. STUDY DESIGN: We constructed 2 decision analysis models using TreeAge software: one modeling induction of labor at 39 weeks of gestation vs expectant management for a group of nulliparous patients with unfavorable cervical examinations and the other modeling induction of labor at 39 weeks of gestation vs expectant management for a group with favorable cervical examinations. Estimates of cost, probability, and health state utility were derived from the literature. Based on previous literature, we assumed that people with favorable cervical examinations would have a lower baseline rate of cesarean delivery and higher rates of spontaneous labor. RESULTS: In our base case analysis, induction of labor at 39 weeks of gestation was cost-effective for patients with unfavorable cervical examinations, but not for patients with favorable cervical examinations. The incremental cost per quality-adjusted life year was 50-fold lower for people with unfavorable cervical examinations ($2150 vs $115,100). Induction of labor resulted in 3885 fewer cesarean deliveries and 58 fewer stillbirths per 100,000 patients for those with unfavorable examinations, whereas induction of labor resulted in 2293 fewer cesarean deliveries and 48 fewer stillbirths with labor induction for those with favorable cervical examinations. The results were sensitive to multiple inputs, including the likelihood of cesarean delivery, the cost of induction, the cost of vaginal or cesarean delivery, and the probability of spontaneous labor. In Monte Carlo analysis, the base case findings held true for 64.1% of modeled scenarios for patients with unfavorable cervixes and 55.4% of modeled scenarios for patients with favorable cervixes. CONCLUSION: With a willingness-to-pay threshold of $100,000 per quality-adjusted life year, induction of labor at 39 weeks of gestation may be cost-effective for patients with unfavorable cervical examinations, but not for patients with favorable cervical examinations. This result was driven by the likelihood of labor in patients with favorable cervical examinations, and the resultant avoidance of prolonged pregnancy and its complications, including hypertensive disorders of pregnancy and stillbirths. Health systems may wish to prioritize patients with unfavorable cervical examinations for elective induction of labor at 39 weeks of gestation, which may be opposite to common practice.

Change in Emergency Medical Services-Attended Out-of-Hospital Deliveries during COVID-19 in the United States.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Epidemiology of Emergency Medical Services-Attended out-of-Hospital Deliveries and Complications in the United States.

BACKGROUND: Prehospital obstetric events, including out-of-hospital deliveries and their complications, are a rare but high-risk event encountered by emergency medical services (EMS). Understanding the epidemiology of these encounters would help identify strategies to improve prehospital obstetric care. Our objective was to determine the characteristics of out-of-hospital deliveries and high-risk complications treated by EMS clinicians in the U.S. METHODS: We conducted a cross-sectional analysis of EMS patient care records in the 2018 and 2019 National EMS Information System Public Release Version 3.4 datasets. We included EMS activations after a 9-1-1 scene response for patients aged 12-50 years with evidence of an out-of-hospital delivery or delivery complication, or where the patient was a newborn aged 0-<6 h. We examined patient, community, emergency response, and clinical characteristics using descriptive statistics. RESULTS: Of the 56,735,977 EMS activations included in the 2018 and 2019 datasets, there were 8,614 out-of-hospital deliveries, 1,712 delivery complications, and 5,749 records for newborns. Most maternal (76%) out-of-hospital deliveries involved patients between the ages of 20-34 years, occurred on a weekday (73%), were treated by an advanced life support crew (85%), and occurred in a home or residence (73%). EMS-assisted field delivery was documented in 3,515 (34%) of all maternal activations but only 2% of activations with a delivery complication. Few patients received an EMS-administered medication (e.g., 0.4% received oxytocin). Supplemental oxygen was administered in 870 (15%) of newborn activations. Activations from counties with the most racial/ethnic diversity were more often treated by a BLS-level unit (16% vs. 12%, p < 0.001), and activations from rural areas had significantly longer transport times (19.7 min [IQR 8.7, 32.8] vs. urban, 13.1 min [IQR 8.7, 19.7], p < 0.001). CONCLUSION: In this large, national repository of EMS patient care records from across the U.S., most activations for out-of-hospital delivery, delivery complication, or a newborn included only routine EMS care. There were potential disparities in level of care, clinical care provided, and measures of access to definitive care based on maternal and community factors. We also identified gaps in current practice, such as for postpartum hemorrhage, that could be addressed with changes in EMS clinical protocols and regulations.

Comparison of Maternal and Neonatal Subspecialty Care Provision by Hospital.

OBJECTIVE: 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. STUDY DESIGN: 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. RESULTS: 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). CONCLUSION: 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. KEY POINTS: · 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..

The Application of a Standard Risk Threshold for the Stratification of Maternal Morbidity among Population Subgroups.

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 <35 years (36.6%), non-White or Hispanic (40.7%), nulliparous (38.9%), and those having a planned vaginal delivery (40.9%) than their counterparts. 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: · Predictive risk models are helpful at condensing complex information into an interpretable output.. · Model performance may vary among different population subgroups.. · Prediction models should be examined for their potential to exacerbate underlying disparities..

Natural language processing of admission notes to predict severe maternal morbidity during the delivery encounter.

BACKGROUND: 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. OBJECTIVE: 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). STUDY DESIGN: 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. RESULTS: There were 13,572 delivery encounters with history and physical notes from hospital A, split between training (Atrain, n=10,250) and testing (Atest, n=3,322) datasets for model derivation and internal validation. There were 23,397 delivery encounters with history and physical notes from hospital B (Bvalid) used for external validation. For the outcome of severe maternal morbidity, the natural language processing model had an area under the receiver operating curve of 0.67 (95% confidence interval, 0.63-0.72) and 0.72 (95% confidence interval, 0.70-0.74) in the Atest and Bvalid datasets, respectively. For the outcome of nontransfusion severe maternal morbidity, the area under the receiver operating curve was 0.72 (95% confidence interval, 0.65-0.80) and 0.76 (95% confidence interval, 0.73-0.79) in the Atest and Bvalid datasets, respectively. The calibration plots demonstrated the bag-of-words model's ability to distinguish a group of individuals at a substantially higher risk of severe maternal morbidity and nontransfusion severe maternal morbidity, notably those in the top deciles of predicted risk. Areas under the receiver operating curve in the natural language processing-based models were similar to those generated using a validated, retrospectively derived, diagnosis code-based comorbidity score. CONCLUSION: In 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.

Prolonged Second Stage of Labor and Anal Sphincter Injury in a Contemporary Cohort of Term Nulliparas.

OBJECTIVE: This study aimed to assess whether a prolonged second stage of labor is an independent predictor of obstetric anal sphincter injury (OASI) in a contemporary cohort of nulliparous and term parturients, and to evaluate whether predelivery factors can accurately predict OASI. STUDY DESIGN: This was a nested case-control study within a cohort of consecutive nulliparous term parturients with a singleton gestation who underwent a vaginal delivery at a single institution between January 2014 and January 2015. Cases were defined as women with a third- or fourth-degree laceration at the time of delivery, and controls were women without a third- or fourth-degree laceration. A prolonged second stage was defined as a second stage of ≥3 hours. Univariable and multivariable regression analyses were performed to examine the relationship between prolonged second stage of labor and third- or fourth-degree lacerations. Receiver operator curves were developed to assess the predictive capacity of predelivery information for third- and fourth-degree lacerations. RESULTS: Of 1,197 births, 63 women had third- or fourth-degree lacerations (5.3%). With each additional hour of the second stage, the rate of OASI increased, with 2.9% of women with a second stage of <1 hour with OASI, 3.5% between 1 and 2 hours, 5.7% between 2 and 3 hours, 7.8% between 3 and 4 hours, 16.1% between 4 and 5 hours, and 28.6% among women with a second stage length >5 hours (p < 0.001). In multivariable regression analysis, operative vaginal delivery (adjusted odds ratio [aOR] = 5.92, 95% confidence interval [CI]: 3.17-11.07) and a prolonged second stage (aOR = 1.92, 95% CI: 1.06-3.51) were independent predictors of third- and fourth-degree lacerations. A predictive model was developed from these results (area under the curve [AUC] = 0.75, 95% CI: 0.68-0.81). CONCLUSION: Prolonged second stage of labor is a predictor of OASI, after adjustment for operative vaginal delivery. A model using predelivery risk factors has a reasonable prediction of OASI. KEY POINTS: · Prolonged second stage labor is associated with obstetric anal sphincter injury in term nulliparas.. · Predelivery risk factors reasonably predict obstetric anal sphincter injury in term nulliparas.. · Improved models are needed for clinical risk-stratification..

Placental Expression of ACE2 and TMPRSS2 in Maternal Severe Acute Respiratory Syndrome Coronavirus 2 Infection: Are Placental Defenses Mediated by Fetal Sex?

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.

Utility of noninvasive genome-wide screening: a prospective cohort of obstetric patients undergoing diagnostic testing.

PURPOSE: Copy-number variant (CNV) assessment is recommended for patients undergoing prenatal diagnostic testing. Noninvasive screening tests have not been extensively validated for CNV detection. The objective of this study was to compare the ability of genome-wide noninvasive prenatal screening (NIPS) to chromosomal microarray to detect clinically significant findings. METHODS: We prospectively enrolled 198 subjects at the time of consent for diagnostic prenatal testing. Genome-wide NIPS results were compared with diagnostic testing results to assess NIPS test performance (n = 160, 38 subjects without microarray results excluded). Cohen's kappa statistic was used to assess test agreement. RESULTS: Genome-wide NIPS did not detect clinically significant chromosomal abnormalities at the same rate as diagnostic testing, κ = 0.75 (95% confidence interval [CI], 0.62-0.87). When excluding CNVs <7 Mb and findings outside the limits of genome-wide NIPS, test agreement improved, κ = 0.88 (0.79-0.97) driven by agreement for common aneuploidies (κ = 1.0). However, among patients with an abnormal fetal survey, agreement was only fair, κ = 0.38 (0.08-0.67). CONCLUSION: While NIPS is an excellent screening test for common aneuploidies, genome-wide NIPS misses clinically significant findings detected on routine diagnostic testing. False positive and false negative cases highlight the importance of pretest counseling regarding NIPS limitations, especially in the setting of fetal anomalies.

Society for Maternal-Fetal Medicine Consult Series #55: Counseling women at increased risk of maternal morbidity and mortality.

Women should be provided with evidence-based information when considering options for contraception and pregnancy management. When counseling about health conditions and available treatments, healthcare practitioners should employ strategies that encourage the incorporation of informed patient preferences into a shared decision-making process with the patient. To optimize the health of women at risk of experiencing adverse health outcomes during or after pregnancy, counseling should be a continuous process throughout the reproductive life course. The purpose of this Consult is to provide guidance for all healthcare practitioners about counseling reproductive-aged women who may be at high risk of experiencing maternal morbidity or mortality.

Postpartum depression screening: Treatment engagement, barriers to care, and change in depressive symptoms.

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.

Frequency and severity of prehospital obstetric events encountered by emergency medical services in the United States.

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.

Association of sexual assault history with traumatic childbirth and subsequent PTSD.

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.

Oxytocin Compared to Buccal Misoprostol for Induction of Labor after Term Prelabor Rupture of Membranes.

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.

Placental pathology in live births conceived with in vitro fertilization after fresh and frozen embryo transfer.

BACKGROUND: The availability and use of frozen embryos after ovarian hyperstimulation for assisted reproduction has increased with improvement in vitrification techniques and the rise of preimplantation genetic testing. However, there are conflicting data regarding whether obstetric outcomes differ between fresh and frozen embryo transfer cycles. OBJECTIVE: To compare placental pathology from live births arising from fresh and frozen embryo transfer cycles. MATERIALS AND METHODS: A cohort of 1140 live births with placental pathology arising from autologous in vitro fertilization cycles with fresh or frozen programmed transfer performed at MGH Fertility Center between 2004 and 2017 was retrospectively reviewed. An experienced placental pathologist categorized the reported placental pathology as anatomic, infectious, inflammatory, or vascular/thrombotic. Our primary outcomes were differences in these placental pathologies between the 2 groups. Patient demographic, cycle, and birth outcomes were compared with the use of χ2 tests, Student t test, or nonparametric tests, as appropriate. Multivariate logistic regression models were used to compare placental pathology between the fresh and frozen transfer groups. RESULTS: Of the 1140 cycles included in our analysis, 929 arose from fresh embryo transfers (81.3%) and 211 arose from programmed frozen embryo transfers (18.5%). For both transfer types, the average age of the women at time of treatment was 35 years; mean body mass indices were within the normal range (23.6 kg/m2 for fresh transfers and 23.2 kg/m2 for frozen transfers, P = .26), and mean day 3 follicle-stimulating hormone values were 7.1 and 7.0 IU/L (P = .44), respectively. Deliveries occurred on average at 37.5 and 38.0 weeks' gestational age (P = .04) in the fresh versus frozen transfer group, with similar rates of obstetric complications. However, frozen transfers were more likely to be associated with marginal cord insertion (adjusted odds ratio, 1.87; confidence interval, 1.21, 2.91; P = .01), accessory lobe formation (adjusted odds ratio, 2.96; confidence interval, 1.12, 7.79; P = 0.03), subchorionic thrombi (adjusted odds ratio, 3.72; confidence interval, 1.80, 7.71; P < .001), and fetal vascular malperfusion characteristics with cord anomalies (adjusted odds ratio, 2.34; confidence interval, 1.22, 4.46; P = .01). These trends persisted when we analyzed day 5 transfers alone, and single frozen embryo transfers remained associated with increased rates of subchorionic thrombi compared to single fresh embryo transfers. CONCLUSION: Pregnancies arising from frozen embryo transfers demonstrated more anatomic and vascular placental pathology than those from fresh transfers in our cohort of patients, despite similar maternal outcomes. More research is needed to explore how these differences in pathology may influence obstetric and perinatal outcomes.

Rapid establishment of a COVID-19 perinatal biorepository: early lessons from the first 100 women enrolled.

BACKGROUND: Collection of biospecimens is a critical first step to understanding the impact of COVID-19 on pregnant women and newborns - vulnerable populations that are challenging to enroll and at risk of exclusion from research. We describe the establishment of a COVID-19 perinatal biorepository, the unique challenges imposed by the COVID-19 pandemic, and strategies used to overcome them. METHODS: A transdisciplinary approach was developed to maximize the enrollment of pregnant women and their newborns into a COVID-19 prospective cohort and tissue biorepository, established on March 19, 2020 at Massachusetts General Hospital (MGH). The first SARS-CoV-2 positive pregnant woman was enrolled on April 2, and enrollment was expanded to SARS-CoV-2 negative controls on April 20. A unified enrollment strategy with a single consent process for pregnant women and newborns was implemented on May 4. SARS-CoV-2 status was determined by viral detection on RT-PCR of a nasopharyngeal swab. Wide-ranging and pregnancy-specific samples were collected from maternal participants during pregnancy and postpartum. Newborn samples were collected during the initial hospitalization. RESULTS: Between April 2 and June 9, 100 women and 78 newborns were enrolled in the MGH COVID-19 biorepository. The rate of dyad enrollment and number of samples collected per woman significantly increased after changes to enrollment strategy (from 5 to over 8 dyads/week, P < 0.0001, and from 7 to 9 samples, P < 0.01). The number of samples collected per woman was higher in SARS-CoV-2 negative than positive women (9 vs 7 samples, P = 0.0007). The highest sample yield was for placenta (96%), umbilical cord blood (93%), urine (99%), and maternal blood (91%). The lowest-yield sample types were maternal stool (30%) and breastmilk (22%). Of the 61 delivered women who also enrolled their newborns, fewer women agreed to neonatal blood compared to cord blood (39 vs 58, P < 0.0001). CONCLUSIONS: Establishing a COVID-19 perinatal biorepository required patient advocacy, transdisciplinary collaboration and creative solutions to unique challenges. This biorepository is unique in its comprehensive sample collection and the inclusion of a control population. It serves as an important resource for research into the impact of COVID-19 on pregnant women and newborns and provides lessons for future biorepository efforts.