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Centers for Disease Control and Prevention data from 2020 demonstrate the continued upward trend in the mean age of pregnant individuals in the United States. Observational studies demonstrate that pregnancy in older individuals is associated with increased risks of adverse pregnancy outcomes-for both the pregnant patient and the fetus-that might differ from those found in younger pregnant populations, even in healthy individuals with no other comorbidities. There are several studies that suggest that advancing age at the time of pregnancy is associated with greater disparities in severe maternal morbidity and mortality. This document seeks to provide evidence-based clinical recommendations for minimizing adverse outcomes associated with pregnancy with anticipated delivery at an advanced maternal age. The importance and benefits of accessible health care from prepregnancy through postpartum care for all pregnant individuals cannot be overstated. However, this document focuses on and addresses the unique differences in pregnancy-related care for women and all those seeking obstetrical care with anticipated delivery at the age of 35 years or older within the framework of routine pregnancy care. This Obstetric Care Consensus document was developed using an a priori protocol in conjunction with the authors listed above.

ImportanceThe prevalence, pathophysiology, and long-term outcomes of COVID-19 (post-acute sequelae of SARS-CoV-2 [PASC] or “Long COVID”) in children and young adults remain unknown. Studies must address the urgent need to define PASC, its mechanisms, and potential treatment targets in children and young adults.ObservationsWe describe the protocol for the Pediatric Observational Cohort Study of the NIH’sREsearchingCOVID toEnhanceRecovery (RECOVER) Initiative. RECOVER-Pediatrics is an observational meta-cohort study of caregiver-child pairs (birth through 17 years) and young adults (18 through 25 years), recruited from more than 100 sites across the US. This report focuses on two of five cohorts that comprise RECOVER-Pediatrics: 1) ade novoRECOVER prospective cohort of children and young adults with and without previous or current infection; and 2) an extant cohort derived from the Adolescent Brain Cognitive Development (ABCD) study (n=10,000). Thede novocohort incorporates three tiers of data collection: 1) remote baseline assessments (Tier 1, n=6000); 2) longitudinal follow-up for up to 4 years (Tier 2, n=6000); and 3) a subset of participants, primarily the most severely affected by PASC, who will undergo deep phenotyping to explore PASC pathophysiology (Tier 3, n=600). Youth enrolled in the ABCD study participate in Tier 1. The pediatric protocol was developed as a collaborative partnership of investigators, patients, researchers, clinicians, community partners, and federal partners, intentionally promoting inclusivity and diversity. The protocol is adaptive to facilitate responses to emerging science.Conclusions and RelevanceRECOVER-Pediatrics seeks to characterize the clinical course, underlying mechanisms, and long-term effects of PASC from birth through 25 years old. RECOVER-Pediatrics is designed to elucidate the epidemiology, four-year clinical course, and sociodemographic correlates of pediatric PASC. The data and biosamples will allow examination of mechanistic hypotheses and biomarkers, thus providing insights into potential therapeutic interventions.Clinical Trials.gov IdentifierClinical Trial Registration:http://www.clinicaltrials.gov. Unique identifier:NCT05172011

ImportancePregnancy induces unique physiologic changes to the immune response and hormonal changes leading to plausible differences in the risk of developing post-acute sequelae of SARS-CoV-2 (PASC), or Long COVID. Exposure to SARS-CoV-2 during pregnancy may also have long-term ramifications for exposed offspring, and it is critical to evaluate the health outcomes of exposed children. The National Institutes of Health (NIH) Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC aims to evaluate the long-term sequelae of SARS-CoV-2 infection in various populations. RECOVER- Pregnancy was designed specifically to address long-term outcomes in maternal-child dyads.MethodsRECOVER-Pregnancy cohort is a combined prospective and retrospective cohort that proposes to enroll 2,300 individuals with a pregnancy during the COVID-19 pandemic and their offspring exposed and unexposed in utero, including single and multiple gestations. Enrollment will occur both in person at 27 sites through theEunice Kennedy ShriverNational Institutes of Health Maternal-Fetal Medicine Units Network and remotely through national recruitment by the study team at the University of California San Francisco (UCSF). Adults with and without SARS-CoV-2 infection during pregnancy are eligible for enrollment in the pregnancy cohort and will follow the protocol for RECOVER-Adult including validated screening tools, laboratory analyses and symptom questionnaires followed by more in-depth phenotyping of PASC on a subset of the overall cohort. Offspring exposed and unexposed in utero to SARS-CoV-2 maternal infection will undergo screening tests for neurodevelopment and other health outcomes at 12, 18, 24, 36 and 48 months of age. Blood specimens will be collected at 24 months of age for SARS-CoV-2 antibody testing, storage and anticipated later analyses proposed by RECOVER and other investigators.DiscussionRECOVER-Pregnancy will address whether having SARS-CoV-2 during pregnancy modifies the risk factors, prevalence, and phenotype of PASC. The pregnancy cohort will also establish whether there are increased risks of adverse long-term outcomes among children exposed in utero.RegistrationNCT05172024

Prescription drug use is prevalent during pregnancy, yet there is limited knowledge about maternal-fetal safety and efficacy of this drug use because pregnant individuals have historically been excluded from clinical trials. Underrepresentation has resulted in a lack of data available to estimate or predict fetal drug exposure. Approaches to study fetal drug pharmacology are limited and must be evaluated for feasibility and accuracy. Anatomic and physiological changes throughout pregnancy fluctuate based on gestational age and can affect drug pharmacokinetics (PK) for both mother and fetus. Drug concentrations have been studied throughout different stages of gestation and at or following delivery in tissue and fluid biospecimens. Sampling amniotic fluid, umbilical cord blood, placental tissue, meconium, umbilical cord tissue, and neonatal hair present surrogate options to quantify and characterize fetal drug exposure. These sampling methods can be applied to all therapeutics including small molecule drugs, large molecule drugs, conjugated nanoparticles, and chemical exposures. Alternative approaches to determine PK have been explored, including physiologically based PK modeling, in vitro methods, and traditional animal models. These alternative approaches along with convenience sampling of tissue or fluid biospecimens can address challenges in studying maternal-fetal pharmacology. In this narrative review, we 1) present an overview of the current understanding of maternal-fetal drug exposure; 2) discuss biospecimen-guided sampling design and methods for measuring fetal drug concentrations throughout gestation; and 3) propose methods for advancing pharmacology research in the maternal-fetal population.

Objective: This sequential, prospective meta-analysis sought to identify risk factors among pregnant and postpartum women with COVID-19 for adverse outcomes related to disease severity, maternal morbidities, neonatal mortality and morbidity, and adverse birth outcomes. Data sources: We prospectively invited study investigators to join the sequential, prospective meta-analysis via professional research networks beginning in March 2020. Study eligibility criteria: Eligible studies included those recruiting at least 25 consecutive cases of COVID-19 in pregnancy within a defined catchment area. Methods: We included individual patient data from 21 participating studies. Data quality was assessed, and harmonized variables for risk factors and outcomes were constructed. Duplicate cases were removed. Pooled estimates for the absolute and relative risk of adverse outcomes comparing those with and without each risk factor were generated using a 2-stage meta-analysis. Results: We collected data from 33 countries and territories, including 21,977 cases of SARS-CoV-2 infection in pregnancy or postpartum. We found that women with comorbidities (preexisting diabetes mellitus, hypertension, cardiovascular disease) vs those without were at higher risk for COVID-19 severity and adverse pregnancy outcomes (fetal death, preterm birth, low birthweight). Participants with COVID-19 and HIV were 1.74 times (95% confidence interval, 1.12-2.71) more likely to be admitted to the intensive care unit. Pregnant women who were underweight before pregnancy were at higher risk of intensive care unit admission (relative risk, 5.53; 95% confidence interval, 2.27-13.44), ventilation (relative risk, 9.36; 95% confidence interval, 3.87-22.63), and pregnancy-related death (relative risk, 14.10; 95% confidence interval, 2.83-70.36). Prepregnancy obesity was also a risk factor for severe COVID-19 outcomes including intensive care unit admission (relative risk, 1.81; 95% confidence interval, 1.26-2.60), ventilation (relative risk, 2.05; 95% confidence interval, 1.20-3.51), any critical care (relative risk, 1.89; 95% confidence interval, 1.28-2.77), and pneumonia (relative risk, 1.66; 95% confidence interval, 1.18-2.33). Anemic pregnant women with COVID-19 also had increased risk of intensive care unit admission (relative risk, 1.63; 95% confidence interval, 1.25-2.11) and death (relative risk, 2.36; 95% confidence interval, 1.15-4.81). Conclusion: We found that pregnant women with comorbidities including diabetes mellitus, hypertension, and cardiovascular disease were at increased risk for severe COVID-19-related outcomes, maternal morbidities, and adverse birth outcomes. We also identified several less commonly known risk factors, including HIV infection, prepregnancy underweight, and anemia. Although pregnant women are already considered a high-risk population, special priority for prevention and treatment should be given to pregnant women with these additional risk factors.

OBJECTIVE To estimate the actual excess costs of care for delivery admissions complicated by severe maternal morbidity (SMM) compared with uncomplicated deliveries. STUDY DESIGN This is a retrospective cohort study of all deliveries between October 2015 and September 2018 at a single tertiary academic center. Pregnant individuals ≥ 20 weeks' gestation who delivered during a hospital admission (i.e., a "delivery admission") were included. The primary exposure was SMM, as defined by Centers for Disease Control and Prevention (CDC) criteria, CDC criteria excluding blood transfusion, or by validated hospital-defined criteria (intensive care unit admission or ≥ 4 units of blood products). Potential SMM events identified via administrative and blood bank data were reviewed to confirm SMM events had occurred. Primary outcome was total actual costs of delivery admission derived from time-based accounting and acquisition costs in the institutional Value Driven Outcomes database. Cost of delivery admissions with SMM events was compared with the cost of uncomplicated delivery using adjusted generalized linear models, with separate models for each of the SMM definitions. Relative cost differences are reported due to data restrictions. RESULTS Of 12,367 eligible individuals, 12,361 had complete cost data. Two hundred and eighty individuals (2.3%) had confirmed SMM events meeting CDC criteria. CDC criteria excluding transfusion alone occurred in 1.0% (n = 121) and hospital-defined SMM in 0.6% (n = 76). In adjusted models, SMM events by CDC criteria were associated with a relative cost increase of 2.45 times (95% confidence interval [CI]: 2.29-2.61) the cost of an uncomplicated delivery. SMM by CDC criteria excluding transfusion alone was associated with a relative increase of 3.26 (95% CI: 2.95-3.60) and hospital-defined SMM with a 4.19-fold (95% CI: 3.64-4.83) increase. Each additional CDC subcategory of SMM diagnoses conferred a relative cost increase of 1.60 (95% CI: 1.43-1.79). CONCLUSION SMM is associated with between 2.5- and 4-fold higher cost than uncomplicated deliveries. KEY POINTS · Severe maternal morbidity as defined by CDC criteria confers a 2.5-fold increase in delivery hospitalization costs.. · Intensive care unit admission or ≥ 4 units of blood products confer a fourfold increase in cost.. · Costs of maternal morbidity may motivate SMM review..

Background The purpose of this study was to estimate prevalence of asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among patients admitted to obstetric inpatient units throughout the United States as detected by universal screening. We sought to describe the relationship between obstetric inpatient asymptomatic infection rates and publicly available surrounding community infection rates. Methods A cross-sectional study in which medical centers reported rates of positive SARS-CoV-2 testing in asymptomatic pregnant and immediate postpartum patients over a 1–3-month time span in 2020. Publicly reported SARS-CoV-2 case rates from the relevant county and state for each center were collected from the COVID Act Now dashboard and the COVID Tracking Project for correlation analysis. Results Data were collected from 9 health centers, encompassing 18 hospitals. Participating health centers were located in Alabama, California, Illinois, Louisiana, New Jersey, North Carolina, Pennsylvania, Rhode Island, Utah, and Washington State. Each hospital had an active policy for universal SARS-CoV-2 testing on obstetric inpatient units. A total of 10 147 SARS-CoV-2 tests were administered, of which 124 were positive (1.2%). Positivity rates varied by site, ranging from 0–3.2%. While SARS-CoV-2 infection rates were lower in asymptomatic obstetric inpatient groups than the surrounding communities, there was a positive correlation between positivity rates in obstetric inpatient units and their surrounding county (P=.003, r=.782) and state (P=.007, r=.708). Conclusions Given the correlation between community and obstetric inpatient rates, the necessity of SARS-CoV-2–related healthcare resource utilization in obstetric inpatient units may be best informed by surrounding community infection rates., There was a significant positive correlation between SARS-CoV-2 positivity rates in obstetric inpatient units and their surrounding county and state. Healthcare resource utilization related to SARS-CoV-2 testing in obstetric inpatient units may be best informed by surrounding community infection rates.

To estimate the association between state-level abortion legislation and all-cause mortality among all females of reproductive age and maternal, fetal, and infant mortality.We conducted a retrospective cohort study using the Centers for Disease Control and Prevention's WONDER (Wide-ranging ONline Data for Epidemiologic Research) database. Generalized estimating equations were used to estimate the association between supportive, moderate, and restrictive state abortion regulations and all-cause mortality in reproductive-aged females. Secondary outcomes included maternal, fetal, and infant mortality. The association of the number and type of laws on mortality were estimated.Moderate and supportive states were not associated with a significant decrease in all-cause mortality compared with restrictive states. Maternal mortality (per 100,000 live births) was significantly lower in moderate (-5.79, 95% CI -9.88 to -1.70) compared with restrictive states, but not supportive states (-2.51, 95% CI -6.75 to 1.72). Infant mortality (per 1,000 live births) was significantly lower in both moderate (-0.56, 95% CI -1.09 to -0.04) and supportive (-1.10, 95% CI -1.56 to -0.64) states. Fetal mortality was lower in moderate states (-0.69, 95% CI -1.18 to -0.20) but not in supportive states (-0.64, 95% CI -1.14 to 0.13). Each additional abortion regulation was associated with an increase in maternal mortality (1.09, 95% CI 0.36-1.82) and infant mortality (95% CI 0.20, 0.12-0.26).Moderate state abortion legislation was associated with lower rates of maternal, fetal, and infant mortality but not lower all-cause mortality in reproductive-aged females compared with restrictive laws. An increasing number of laws restricting abortion was associated with increased maternal and infant mortality.

Care for pregnant patients with substance use disorder must be provided in a nonjudgmental manner with recognition of addiction as a chronic medical illness in order to establish a therapeutic relationship and improve outcomes. All pregnant patients should be screened for substance use during prenatal care. Screening can be accomplished through several validated screening tools. Patients who screen positive need to be evaluated and referred for treatment as appropriate. This article reviews specific adverse perinatal outcomes associated with the use of a variety of substances and provides guidance on exposure with continued breastfeeding.

Objective Randomized controlled trials (RCTs) are considered the highest level of evidence to inform clinical practice. However, the reproducibility crisis has raised concerns about the scientific rigor of published RCT findings. Some advocate for a lower p-value threshold. We aimed to review published OB/Gyn topical RCTs in three representative OB/Gyn journals and three high impact non-OB/Gyn journals to determine if their interpretations would change with adoption of a p-value threshold for significance of 0.005. Secondarily, we evaluated if there were differences in methodologic characteristics between those that did and did not lose significance. Study Design A manual search was performed to identify all OB/Gyn RCTs published in the selected journals between July 2017 and June 2019. Data were collected on primary outcome(s), methodology, and p-values. We determined the proportion of primary outcomes that would remain statistically significant with adoption of a p-value significance threshold of 0.005 versus be reinterpreted as “suggestive” (defined as p-value between 0.005 and 0.05). Chi-square or Fisher's exact test were used to compare study characteristics. Results Overall, 202 RCTs met inclusion criteria; 52% in obstetrics and 48% in gynecology. Of 90 studies considered significant with p Conclusion Adopting a p-value significance threshold of 0.005 would require reinterpretation of almost half of RCT results in the OB/Gyn literature. Highly variable methodological quality was identified. Key Points

We aimed to evaluate whether delivering during the early the coronavirus disease 2019 (COVID-19) pandemic was associated with increased risk of maternal death or serious morbidity from common obstetric complications compared with a historical control period.This was a multicenter retrospective cohort study with manual medical-record abstraction performed by centrally trained and certified research personnel at 17 U.S. hospitals. Individuals who gave birth on randomly selected dates in 2019 (before the pandemic) and 2020 (during the pandemic) were compared. Hospital, health care system, and community risk-mitigation strategies for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in response to the early COVID-19 pandemic are described. The primary outcome was a composite of maternal death or serious morbidity from common obstetric complications, including hypertensive disorders of pregnancy (eclampsia, end organ dysfunction, or need for acute antihypertensive therapy), postpartum hemorrhage (operative intervention or receipt of 4 or more units blood products), and infections other than SARS-CoV-2 (sepsis, pelvic abscess, prolonged intravenous antibiotics, bacteremia, deep surgical site infection). The major secondary outcome was cesarean birth.Overall, 12,133 patients giving birth during and 9,709 before the pandemic were included. Hospital, health care system, and community SARS-CoV-2 mitigation strategies were employed at all sites for a portion of 2020, with a peak in modifications from March to June 2020. Of patients delivering during the pandemic, 3% had a positive SARS-CoV-2 test result during pregnancy through 42 days postpartum. Giving birth during the pandemic was not associated with a change in the frequency of the primary composite outcome (9.3% vs 8.9%, adjusted relative risk [aRR] 1.02, 95% CI 0.93-1.11) or cesarean birth (32.4% vs 31.3%, aRR 1.02, 95% CI 0.97-1.07). No maternal deaths were observed.Despite substantial hospital, health care, and community modifications, giving birth during the early COVID-19 pandemic was not associated with higher rates of serious maternal morbidity from common obstetric complications.ClinicalTrials.gov, NCT04519502.

Objective Physical examination–indicated cerclage for cervical insufficiency prolongs gestation, but evidence on the addition of adjuncts to further prolong latency is limited. The aim of this systematic review and meta-analysis was to compare gestational latency between those who did and did not receive adjunct antibiotic or tocolytic therapy at the time of examination-indicated cerclage. Study Design Electronic databases (1966–2020) were searched for randomized controlled trials (RCTs) and cohort studies comparing adjunct antibiotic or tocolytic use versus nonuse at time of examination-indicated cerclage, defined as placement for cervical dilation ≥1 cm, in a current singleton pregnancy. Studies including individuals with intra-amniotic infection, cerclage in place, nonviable gestation, or ruptured membranes were excluded. The primary outcome was latency from cerclage placement to delivery. Secondary outcomes included preterm birth, preterm premature rupture of membranes, birth weight, and neonatal survival. Risk of bias was assessed using standardized tools. Heterogeneity was assessed using χ 2 and I 2 tests. Results were pooled and analyzed using a random-effects model. This study is registered with The International Prospective Register of Systematic Reviews (PROSPERO) with registration no.: CRD42021216370. Results Of 923 unique records, 163 were reviewed in full. Three met inclusion criteria: one RCT and two retrospective cohorts. The included RCT (n = 50) and one cohort (n = 142) compared outcomes with and without adjunct use of antibiotic and tocolytic, while the second cohort (n = 150) compared outcomes with and without adjunct tocolytic, with a subpopulation also receiving antibiotics. The RCT was nested within one of the cohorts, and therefore only one of these two studies was utilized for any given outcome to eliminate counting individuals twice. Risk of bias was “critical” for one cohort study, “moderate” for the other cohort study, and “some concerns” for the RCT. Gestational latency could not be pooled and meta-analyzed. Adjunct tocolytic-antibiotic therapy was not associated with a decrease in risk of preterm delivery Conclusion There is not enough evidence to robustly evaluate the use of adjunct tocolytics or antibiotics at time of examination-indicated cerclage to prolong latency. Key Points

The Society for Maternal-Fetal Medicine Publications Committee first adopted the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system in 2013. This document provides an update on the Society for Maternal-Fetal Medicine Publications Committee process for creating evidence-based practice recommendations and describes the GRADE process as it is currently implemented in the SMFM Consult and Guidelines series.

Pregnant patients with severe or critical coronavirus disease 2019 (COVID-19), but not those with mild or moderate COVID-19, were at increased risk for perinatal complications compared with asymptomatic patients., OBJECTIVE: To describe coronavirus disease 2019 (COVID-19) severity in pregnant patients and evaluate the association between disease severity and perinatal outcomes. METHODS: We conducted an observational cohort study of all pregnant patients with a singleton gestation and a positive test result for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who delivered at 1 of 33 U.S. hospitals in 14 states from March 1 to July 31, 2020. Disease severity was classified by National Institutes of Health criteria. Maternal, fetal, and neonatal outcomes were abstracted by centrally trained and certified perinatal research staff. We evaluated trends in maternal characteristics and outcomes across COVID-19 severity classes and associations between severity and outcomes by multivariable modeling. RESULTS: A total of 1,219 patients were included: 47% asymptomatic, 27% mild, 14% moderate, 8% severe, 4% critical. Overall, 53% were Hispanic; there was no trend in race–ethnicity distribution by disease severity. Those with more severe illness had older mean age, higher median body mass index, and pre-existing medical comorbidities. Four maternal deaths (0.3%) were attributed to COVID-19. Frequency of perinatal death or a positive neonatal SARS-CoV-2 test result did not differ by severity. Adverse perinatal outcomes were more frequent among patients with more severe illness, including 6% (95% CI 2–11%) incidence of venous thromboembolism among those with severe–critical illness compared with 0.2% in mild–moderate and 0% in asymptomatic (P

SARS-CoV-2 infection during pregnancy is associated with adverse pregnancy outcomes, including fetal death and preterm birth. It is not known whether that risk occurs only during the time of acute infection or whether the risk persists later in pregnancy.This study aimed to evaluate whether the risk of SARS-CoV-2 infection during pregnancy persists after an acute maternal illness.A retrospective cohort study of pregnant patients with and without SARS-CoV-2 infection delivering at 17 hospitals in the United States between March 2020 and December 2020. Patients experiencing a SARS-CoV-2-positive test at or before 28 weeks of gestation with a subsequent delivery hospitalization were compared with those without a positive SAR-CoV-2 test at the same hospitals with randomly selected delivery days during the same period. Deliveries occurring at20 weeks of gestation in both groups were excluded. The study outcomes included fetal or neonatal death, preterm birth at37 weeks of gestation and34 weeks of gestation, hypertensive disorders of pregnancy (HDP), any major congenital malformation, and size for gestational age of5th or10th percentiles at birth based on published standards. HDP that were collected included HDP and preeclampsia with severe features, both overall and with delivery at37 weeks of gestation.Of 2326 patients who tested positive for SARS-CoV-2 during pregnancy and were at least 20 weeks of gestation at delivery from March 2020 to December 2020, 402 patients (delivering 414 fetuses or neonates) were SARS-CoV-2 positive before 28 weeks of gestation and before their admission for delivery; they were compared with 11,705 patients without a positive SARS-CoV-2 test. In adjusted analyses, those with SARS-CoV-2 before 28 weeks of gestation had a subsequent increased risk of fetal or neonatal death (2.9% vs 1.5%; adjusted relative risk, 1.97; 95% confidence interval, 1.01-3.85), preterm birth at37 weeks of gestation (19.6% vs 13.8%; adjusted relative risk, 1.29; 95% confidence interval, 1.02-1.63), and HDP with delivery at37 weeks of gestation (7.2% vs 4.1%; adjusted relative risk, 1.74; 95% confidence interval, 1.19-2.55). There was no difference in the rates of preterm birth at34 weeks of gestation, any major congenital malformation, and size for gestational age of5th or10th percentiles. In addition, there was no significant difference in the rate of gestational hypertension overall or preeclampsia with severe features.There was a modest increase in the risk of adverse pregnancy outcomes after SARS-CoV-2 infection.

OBJECTIVE To study the association between nicotine or cannabis metabolite presence in maternal urine and child neurodevelopmental outcomes. METHODS We conducted a secondary analysis of two parallel multicenter randomized controlled trials of treatment for hypothyroxinemia or subclinical hypothyroidism among pregnant individuals enrolled at 8-20 weeks of gestation. All maternal-child dyads with a maternal urine sample at enrollment and child neurodevelopmental testing were included (N=1,197). Exposure was urine samples positive for nicotine (cotinine) or cannabis 11-nor-9-carboxy-delta-9-tetrahydrocannabinol [THC-COOH]) or both metabolites. Primary outcome was child IQ at 60 months. Secondary outcomes included cognitive, motor and language, attention, behavioral and social competency, and differential skills assessments at 12, 24, 36, and 48 months. Quantile regression analysis was performed with confounder adjustment. RESULTS Of 1,197 pregnant individuals, 99 (8.3%) had positive cotinine samples and 47 (3.9%) had positive THC-COOH samples; 33 (2.8%) were positive for both. Groups differed in self-reported race and ethnicity, education, marital status, insurance, and thyroid status. Median IQ was similar between cotinine-exposed and -unexposed children (90 vs 95, adjusted difference in medians -2.47, 95% CI -6.22 to 1.29) and THC-COOH-exposed and -unexposed children (89 vs 95, adjusted difference in medians -1.35, 95% CI -7.76 to 5.05). In secondary outcome analysis, children with THC-COOH exposure compared with those unexposed had higher attention scores at 48 months of age (57 vs 49, adjusted difference in medians 6.0, 95% CI 1.11-10.89). CONCLUSIONS Neither prenatal nicotine nor cannabis exposure was associated with a difference in IQ. Cannabis exposure was associated with worse attention scores in early childhood. Longitudinal studies assessing associations between child neurodevelopmental outcomes and prenatal nicotine and cannabis exposure with a focus on timing and quantity of exposure are needed. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov, NCT00388297.

OBJECTIVE Marijuana use is associated with placenta-mediated adverse pregnancy outcomes including fetal growth restriction, but the mechanism remains uncertain. The objective was to evaluate the association between maternal marijuana use and the feto-placental weight ratio (FPR). Secondarily, we aimed to compare placental histology of women who used marijuana to those who did not. STUDY DESIGN This was a secondary analysis of singleton pregnancies enrolled in a multicenter and case-control stillbirth study. Prior marijuana use was detected by electronic medical record abstraction or cord homogenate positive for 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid. Prior tobacco use was detected by self-report or presence of maternal serum cotinine. Stillbirths and live births were considered separately. The primary outcome was FPR. Association of marijuana use with FPR was estimated with multivariable linear modeling adjusted for fetal sex, preterm birth, and tobacco use. Comparisons between groups for placental histology were made using Chi-square and stratified by live birth and stillbirth, term and preterm deliveries, and fetal sex. RESULTS Of 1,027 participants, 224 were stillbirths and 803 were live births. Overall, 41 (4%) women used marijuana during the pregnancy. The FPR ratio was lower among exposed offspring but reached statistical significance only for term stillbirths (mean 6.84 with marijuana use vs. mean 7.8 without use, p

OBJECTIVE To estimate the proportion of accidental drug-related deaths and suicides classified as pregnancy-related from 2013 to 2014 (preimplementation of standardized criteria) and 2015 to 2016 (postimplementation). METHODS Based on Centers for Disease Control and Prevention pregnancy-related death criteria, the Utah Perinatal Mortality Review Committee developed a standardized evaluation tool to assess accidental drug-related death and suicide beginning in 2015. We performed a retrospective case review of all pregnancy-associated deaths (those occurring during pregnancy or 1 year postpartum for any reason) and pregnancy-related deaths (those directly attributable to the pregnancy or postpartum events) evaluated by Utah's Perinatal Mortality Review Committee from 2013 to 2016. We compared the proportion of accidental drug-related deaths and suicides meeting pregnancy-related criteria preimplementation and postimplementation of a standardized criteria checklist tool using Fisher's exact test. We assessed the change in pregnancy-related mortality ratio in Utah from 2013 to 2014 and 2015 to 2016 using test of trend. RESULTS From 2013 to 2016, there were 80 pregnancy-associated deaths in Utah (2013-2014: n=40; 2015-2016: n=40), and 41 (51%) were pregnancy-related (2013-2014: n=15, 2015-2016: n=26). In 2013-2014 (preimplementation), 12 women died of drug-related deaths or suicides, and only two of these deaths were deemed pregnancy-related (17%). In 2015-2016 (postimplementation), 18 women died of drug-related deaths or suicide, and 94% (n=17/18) of these deaths met one or more of the pregnancy-related criteria on the checklist (P

Venous thromboembolism is a major cause of maternal morbidity and mortality. The risk of venous thromboembolism is particularly elevated during the postpartum period and especially after cesarean delivery. There is considerable variation in the approach to prophylaxis of venous thromboembolism in pregnancy, including after cesarean delivery. This Consult discusses the different guidelines on prophylaxis of venous thromboembolism after cesarean delivery and provides recommendations based on the available evidence. The recommendations by the Society for Maternal-Fetal Medicine are as follows: (1) we recommend that all women who undergo cesarean delivery receive sequential compression devices starting before surgery and that the compression devices be used continuously until the patient is fully ambulatory (GRADE 1C); (2) we suggest that women with a previous personal history of deep venous thrombosis or pulmonary embolism who undergo cesarean delivery receive both mechanical (starting preoperatively and continuing until ambulatory) and pharmacologic (for 6 weeks postoperatively) prophylaxis (GRADE 2C); (3) we suggest that women with a personal history of an inherited thrombophilia (high-risk or low-risk) but no previous thrombosis who undergo cesarean delivery receive both mechanical (starting preoperatively and continuing until ambulatory) and pharmacologic (for 6 weeks postoperatively) prophylaxis (GRADE 2C); (4) we recommend the use of low-molecular-weight heparin as the preferred thromboprophylactic agent in pregnancy and the postpartum period (GRADE 1C); (5) when pharmacologic thromboprophylaxis is needed in pregnant women with class III obesity, we suggest the use of intermediate doses of enoxaparin (GRADE 2C); and (6) we recommend that each institution develop a patient safety bundle with an institutional protocol for venous thromboembolism prophylaxis among women who undergo cesarean delivery (Best Practice).

Stillbirth is one of the most common adverse pregnancy outcomes, occurring in 1 in 160 deliveries in the United States. In developed countries, the most prevalent risk factors associated with stillbirth are non-Hispanic black race, nulliparity, advanced maternal age, obesity, preexisting diabetes, chronic hypertension, smoking, alcohol use, having a pregnancy using assisted reproductive technology, multiple gestation, male fetal sex, unmarried status, and past obstetric history. Although some of these factors may be modifiable (such as smoking), many are not. The study of specific causes of stillbirth has been hampered by the lack of uniform protocols to evaluate and classify stillbirths and by decreasing autopsy rates. In any specific case, it may be difficult to assign a definite cause to a stillbirth. A significant proportion of stillbirths remains unexplained, even after a thorough evaluation. Evaluation of a stillbirth should include fetal autopsy; gross and histologic examination of the placenta, umbilical cord, and membranes; and genetic evaluation. The method and timing of delivery after a stillbirth depend on the gestational age at which the death occurred, maternal obstetric history (eg, previous hysterotomy), and maternal preference. Health care providers should weigh the risks and benefits of each strategy in a given clinical scenario and consider available institutional expertise. Patient support should include emotional support and clear communication of test results. Referral to a bereavement counselor, peer support group, or mental health professional may be advisable for management of grief and depression.

Our primary objective was to estimate statewide prenatal substance exposure based on umbilical cord sampling. Our secondary objectives were to compare prevalence of prenatal substance exposure across urban, rural, and frontier regions, and to compare contemporary findings to those previously reported.We performed a cross-sectional prevalence study of prenatal substance exposure, as determined by umbilical cord positivity for 49 drugs and drug metabolites, through the use of qualitative liquid chromatography-tandem mass spectrometry. All labor and delivery units in Utah (N=45) were invited to participate. Based on a 2010 study using similar methodology, we calculated that a sample size of at least 1,600 cords would have 90% power to detect 33% higher rate of umbilical cords testing positive for any substance. Deidentified umbilical cords were collected from consecutive deliveries at participating hospitals. Prevalence of prenatal substance exposure was estimated statewide and by rurality using weighted analysis.From November 2020 to November 2021, 1,748 cords (urban n=988, rural n=384, frontier n=376) were collected from 37 hospitals, representing 92% of hospitals that conduct 91% of births in the state. More than 99% of cords (n=1,739) yielded results. Statewide, 9.9% (95% CI 8.1-11.7%) were positive for at least one substance, most commonly opioids (7.0%, 95% CI 5.5-8.5%), followed by cannabinoid (11-nor-9-carboxy-delta-9-tetrahydrocannabinol [THC-COOH]) (2.5%, 95% CI 1.6-3.4%), amphetamines (0.9%, 95% CI 0.4-1.5), benzodiazepines (0.5%, 95% CI 0.1-0.9%), alcohol (0.4%, 95% CI 0.1-0.7%), and cocaine (0.1%, 95% CI 0-0.3%). Cord positivity was similar by rurality (urban=10.3%, 95% CI 8.3-12.3%, rural=7.1%, 95% CI 3.5-10.7%, frontier=9.2%, 95% CI 6.2-12.2%, P=.31) and did not differ by substance type. Compared with a previous study, prenatal exposure to any substance (6.8 vs 9.9%, P=.01), opioids (4.7 vs 7.0% vs 4.7%, P=.03), amphetamines (0.1 vs 0.9%, P=.01) and THC-COOH (0.5 vs 2.5%, P.001) increased.Prenatal substance exposure was detected in nearly 1 in 10 births statewide.

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

OBJECTIVE: Marijuana (MJ) use is associated with adverse effects on fetal growth. We aimed to investigate the timing of suboptimal fetal growth onset in MJ-exposed pregnancies. In addition, we aimed to explore the relationship between MJ-exposure and both abnormal uterine artery (UtA) Doppler parameters and small for gestational age (SGA). STUDY DESIGN: This was a secondary analysis of a prospective multicenter cohort that enrolled nulliparous individuals delivering non-anomalous fetuses beyond 20 weeks’ gestation. Marijuana exposure was ascertained by self-report or clinical urine toxicology testing. Ultrasound estimated fetal weights (EFWs) were assessed in participants at both 16w0d–21w6d and 22w0d–29w6d. EFWs and birth weight (BW) were converted to weight percentiles (wPCT). EFW and BW wPCTs were calculated using population-based standards. Additionally, a customized standard designed to be applicable to both EFWs and BWs within the same model was also used to allow for EFW to BW percentile trajectories. The primary outcome, longitudinal wPCT, was compared between individuals with and without MJ use in a linear mixed-effects regression model adjusting for tobacco. For modeling, wPCT was smoothed across gestational age; MJ was estimated as an intercept and linear difference in the slope of gestational age. UtA Doppler notching, resistance index (RI), and pulsatility index (PI) at 16w0d–21w6d were compared using t-test and χ(2). SGA at delivery was also compared. RESULTS: Nine thousand one hundred and sixty-three individuals met inclusion criteria; 136 (1.5%) used MJ during pregnancy. Individuals who used MJ were more likely to be younger, identify as non-Hispanic Black, and have had less education. Fetuses exposed to MJ had lower wPCT beginning at 28 weeks using population-based and customized standards, when compared to those without exposure. UtA notching, PI, and RI were similar between groups. SGA was more frequent in neonates exposed to MJ using both population-based (22 vs. 9%, p