Nonadjuvanted Bivalent Respiratory Syncytial Virus Vaccination and Perinatal Outcomes.

Importance: A nonadjuvanted bivalent respiratory syncytial virus (RSV) prefusion F (RSVpreF [Pfizer]) protein subunit vaccine was newly approved and recommended for pregnant individuals at 32 0/7 to 36 6/7 weeks' gestation during the 2023 to 2024 RSV season; however, clinical vaccine data are lacking. Objective: To evaluate the association between prenatal RSV vaccination status and perinatal outcomes among patients who delivered during the vaccination season. Design, Setting, and Participants: This retrospective observational cohort study was conducted at 2 New York City hospitals within 1 health care system among patients who gave birth to singleton gestations at 32 weeks' gestation or later from September 22, 2023, to January 31, 2024. Exposure: Prenatal RSV vaccination with the RSVpreF vaccine captured from the health system's electronic health records. Main Outcome and Measures: The primary outcome is preterm birth (PTB), defined as less than 37 weeks' gestation. Secondary outcomes included hypertensive disorders of pregnancy (HDP), stillbirth, small-for-gestational age birth weight, neonatal intensive care unit (NICU) admission, neonatal respiratory distress with NICU admission, neonatal jaundice or hyperbilirubinemia, neonatal hypoglycemia, and neonatal sepsis. Logistic regression models were used to estimate odds ratios (ORs), and multivariable logistic regression models and time-dependent covariate Cox regression models were performed. Results: Of 2973 pregnant individuals (median [IQR] age, 34.9 [32.4-37.7] years), 1026 (34.5%) received prenatal RSVpreF vaccination. Fifteen patients inappropriately received the vaccine at 37 weeks' gestation or later and were included in the nonvaccinated group. During the study period, 60 patients who had evidence of prenatal vaccination (5.9%) experienced PTB vs 131 of those who did not (6.7%). Prenatal vaccination was not associated with an increased risk for PTB after adjusting for potential confounders (adjusted OR, 0.87; 95% CI, 0.62-1.20) and addressing immortal time bias (hazard ratio [HR], 0.93; 95% CI, 0.64-1.34). There were no significant differences in pregnancy and neonatal outcomes based on vaccination status in the logistic regression models, but an increased risk of HDP in the time-dependent model was seen (HR, 1.43; 95% CI, 1.16-1.77). Conclusions and Relevance: In this cohort study of pregnant individuals who delivered at 32 weeks' gestation or later, the RSVpreF vaccine was not associated with an increased risk of PTB and perinatal outcomes. These data support the safety of prenatal RSVpreF vaccination, but further investigation into the risk of HDP is warranted.

COVID-19 Vaccination in the First Trimester and Major Structural Birth Defects Among Live Births.

Importance: COVID-19 vaccination is recommended throughout pregnancy to prevent pregnancy complications and adverse birth outcomes associated with COVID-19 disease. To date, data on birth defects after first-trimester vaccination are limited. Objective: To evaluate the associated risks for selected major structural birth defects among live-born infants after first-trimester receipt of a messenger RNA (mRNA) COVID-19 vaccine. Design, Setting, and Participants: This was a retrospective cohort study of singleton pregnancies with estimated last menstrual period (LMP) between September 13, 2020, and April 3, 2021, and ending in live birth from March 5, 2021, to January 25, 2022. Included were data from 8 health systems in California, Oregon, Washington, Colorado, Minnesota, and Wisconsin in the Vaccine Safety Datalink. Exposures: Receipt of 1 or 2 mRNA COVID-19 vaccine doses in the first trimester, as part of the primary series. Main Outcomes and Measures: Selected major structural birth defects among live-born infants, identified from electronic health data using validated algorithms, with neural tube defects confirmed via medical record review. Results: Among 42 156 eligible pregnancies (mean [SD] maternal age, 30.9 [5.0] years) 7632 (18.1%) received an mRNA COVID-19 vaccine in the first trimester. Of 34 524 pregnancies without a first-trimester COVID-19 vaccination, 2045 (5.9%) were vaccinated before pregnancy, 13 494 (39.1%) during the second or third trimester, and 18 985 (55.0%) were unvaccinated before or during pregnancy. Compared with pregnant people unvaccinated in the first trimester, those vaccinated in the first trimester were older (mean [SD] age, 32.3 [4.5] years vs 30.6 [5.1] years) and differed by LMP date. After applying stabilized inverse probability weighting, differences in baseline characteristics between vaccinated and unvaccinated pregnant persons in the first trimester were negligible (standardized mean difference <0.20). Selected major structural birth defects occurred in 113 infants (1.48%) after first-trimester mRNA COVID-19 vaccination and in 488 infants (1.41%) without first-trimester vaccine exposure; the adjusted prevalence ratio was 1.02 (95% CI, 0.78-1.33). In secondary analyses, with major structural birth defect outcomes grouped by organ system, no significant differences between infants vaccinated or unvaccinated in the first trimester were identified. Conclusions and Relevance: In this multisite cohort study, among live-born infants, first-trimester mRNA COVID-19 vaccine exposure was not associated with an increased risk for selected major structural birth defects.

Coronavirus Disease 2019 (COVID-19) Vaccination and Stillbirth in the Vaccine Safety Datalink.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) vaccination is recommended in pregnancy to reduce the risk of severe morbidity from COVID-19. However, vaccine hesitancy persists among pregnant people, with risk of stillbirth being a primary concern. Our objective was to examine the association between COVID-19 vaccination and stillbirth. METHODS: We performed a matched case-control study in the Vaccine Safety Datalink (VSD). Stillbirths and live births were selected from singleton pregnancies among persons aged 16-49 years with at least one prenatal, delivery, or postpartum visit at eight participating VSD sites. Stillbirths identified through diagnostic codes were adjudicated to confirm the outcome, date, and gestational age at fetal death. Confirmed antepartum stillbirths that occurred between February 14, 2021, and February 27, 2022, then were matched 1:3 to live births by pregnancy start date, VSD site, and maternal age at delivery. Associations among antepartum stillbirth and COVID-19 vaccination in pregnancy, vaccine manufacturer, number of vaccine doses received, and vaccination within 6 weeks before stillbirth (or index date in live births) were evaluated using conditional logistic regression. RESULTS: In the matched analysis of 276 confirmed antepartum stillbirths and 822 live births, we found no association between COVID-19 vaccination during pregnancy and stillbirth (38.4% stillbirths vs 39.3% live births in vaccinated individuals, adjusted odds ratio [aOR] 1.02, 95% CI, 0.76-1.37). Furthermore, no association between COVID-19 vaccination and stillbirth was detected by vaccine manufacturer (Moderna: aOR 1.00, 95% CI, 0.62-1.62; Pfizer-BioNTech: aOR 1.00, 95% CI, 0.69-1.43), number of vaccine doses received during pregnancy (1 vs 0: aOR 1.17, 95% CI, 0.75-1.83; 2 vs 0: aOR 0.98, 95% CI, 0.81-1.17), or COVID-19 vaccination within the 6 weeks before stillbirth or index date compared with no vaccination (aOR 1.16, 95% CI, 0.74-1.83). CONCLUSION: No association was found between COVID-19 vaccination and stillbirth. These findings further support recommendations for COVID-19 vaccination in pregnancy.

Does reversible postpartum contraception reduce the risk of pregnancy condition recurrence? A longitudinal claims-based study from Maine.

PURPOSE: To estimate the effect of reversible postpartum contraception use on the risk of recurrent pregnancy condition in the subsequent pregnancy and if this effect was mediated through lengthening the interpregnancy interval (IPI). METHODS: We used data from the Maine Health Data Organization's Maine All Payer Claims dataset. Our study population was Maine women with a livebirth index pregnancy between 2007 and 2019 that was followed by a subsequent pregnancy starting within 60 months of index pregnancy delivery. We examined recurrence of three pregnancy conditions, separately, in groups that were not mutually exclusive: prenatal depression, hypertensive disorders of pregnancy (HDP), and gestational diabetes (GDM). Effective reversible postpartum contraception use was defined as any intrauterine device, implant, or moderately effective method (pills, patch, ring, injectable) initiated within 60 days of delivery. Short IPI was defined as ≤ 12 months. We used log-binomial regression models to estimate risk ratios and 95 % confidence intervals, adjusting for potential confounders. RESULTS: Approximately 41 % (11,448/28,056) of women initiated reversible contraception within 60 days of delivery, the prevalence of short IPI was 26 %, and the risk of pregnancy condition recurrence ranged from 38 % for HDP to 55 % for prenatal depression. Reversible contraception initiation within 60 days of delivery was not associated with recurrence of the pregnancy condition in the subsequent pregnancy (aRR ranged from 0.97 to 1.00); however, it was associated with lower risk of short IPI (aRR ranged from 0.67 to 0.74). CONCLUSION(S): Although initiation of postpartum reversible contraception within 60 days of delivery lengthens the IPI, our findings suggest that it does not reduce the risk of prenatal depression, HDP, or GDM recurrence. This indicates a missed opportunity for providing evidence-based healthcare and health interventions in the intrapartum period to reduce the risk of recurrence.

Reporting Perinatal Substance Use to Child Protective Services: Obstetric Provider Perspectives on the Impact on Care.

Objective: To understand obstetric provider perspectives on child protective services (CPS)-mandated reporting requirements and how they affect care for pregnant and postpartum patients with opioid use disorder (OUD). Methods: Key informant interviews were conducted virtually with obstetricians, nurse practitioners, and social workers caring for obstetric patients (n = 12). Providers were asked about their experience as mandated reporters working with patients with OUD. Transcripts were independently coded by two staff, and content analysis was used to identify themes. Results: Our analysis resulted in six thematic areas, including CPS-mandated strengths, concerns related to CPS reporting requirements, implementation of mandates, supporting patients after CPS report, communication between stakeholders, and the impact on care. Providers noted that the fear of CPS involvement causes some patients to delay or not engage in care. Other patients are hesitant to accept medications for OUD for fear of CPS involvement. The inconsistencies in how reporting mandates are applied and how CPS handles cases make communication about the policies challenging for providers and create anxiety for patients. Conclusions: The results of this study indicate that mandated reporting requirements and the potential for CPS involvement are perceived to have minimal positive effects on perinatal individuals with OUD and may negatively affect patients and their care. Clinicaltrials.gov number: NCT04240392.

Association between gestational diabetes and cardiovascular disease within 24 months postpartum.

BACKGROUND: Cardiovascular disease is the leading cause of death among women in the United States. It is well established that gestational diabetes mellitus is associated with an overall lifetime increased risk of cardiometabolic disease, even among those without intercurrent type 2 diabetes. However, the association between gestational diabetes mellitus and short-term risk of cardiovascular disease is unclear. Establishing short-term risks of cardiovascular disease for patients with gestational diabetes mellitus has significant potential to inform early screening and targeted intervention strategies to reduce premature cardiovascular morbidity among women. OBJECTIVE: This study aimed to compare the risk of cardiovascular disease diagnosis in the first 24 months postpartum between patients with and without gestational diabetes mellitus. STUDY DESIGN: Our longitudinal population-based study included pregnant individuals with deliveries from 2007 to 2019 in the Maine Health Data Organization's All Payer Claims Database. We excluded records with gestational age <20 weeks, non-Maine residence, multifetal gestation, no insurance in the month of delivery or the 3 months before pregnancy, an implausibly short interval until next pregnancy (<60 days), pregestational diabetes mellitus, and any prepregnancy diagnosis of the cardiovascular conditions being examined postpartum. Gestational diabetes mellitus and cardiovascular disease (heart failure, ischemic heart disease, arrhythmia/cardiac arrest, cardiomyopathy, cerebrovascular disease/stroke, and new chronic hypertension) were identified by International Classification of Diseases 9/10 diagnosis codes. Cox proportional hazards models were used to estimate hazard ratios, adjusting for potential confounding factors. We assessed whether the association between gestational diabetes mellitus and chronic hypertension was mediated by intercurrent diabetes mellitus. RESULTS: Among the 84,746 pregnancies examined, the cumulative risk of cardiovascular disease within 24 months postpartum for those with vs without gestational diabetes mellitus was 0.13% vs 0.20% for heart failure, 0.16% vs 0.14% for ischemic heart disease, 0.60% vs 0.44% for cerebrovascular disease/stroke, 0.22% vs 0.16% for arrhythmia/cardiac arrest, 0.20% vs 0.20% for cardiomyopathy, and 4.19% vs 1.83% for new chronic hypertension. After adjusting for potential confounders, those with gestational diabetes had an increased risk of new chronic hypertension (adjusted hazard ratio, 1.56; 95% confidence interval, 1.32-1.86) within the first 24 months postpartum compared with those without gestational diabetes. There was no association between gestational diabetes and ischemic heart disease (adjusted hazard ratio, 0.75; 95% confidence interval, 0.34-1.65), cerebrovascular disease/stroke (adjusted hazard ratio, 1.13; 95% confidence interval, 0.78-1.66), arrhythmia/cardiac arrest (adjusted hazard ratio, 1.16; 95% confidence interval, 0.59-2.29), or cardiomyopathy (adjusted hazard ratio, 0.75; 95% confidence interval, 0.40-1.41) within the first 24 months postpartum. Those with gestational diabetes appeared to have a decreased risk of heart failure within 24 months postpartum (adjusted hazard ratio, 0.45; 95% confidence interval, 0.21-0.98). Our mediation analyses estimated that 28% of the effect of gestational diabetes on new chronic hypertension was mediated through intercurrent diabetes mellitus. CONCLUSION: Patients with gestational diabetes mellitus have a significantly increased risk of new chronic hypertension as early as 24 months postpartum. Most of this effect was not due to the development of diabetes mellitus. Our findings suggest that all women with gestational diabetes need careful monitoring and screening for new chronic hypertension in the first 2 years postpartum.

Obstetric Complications and Birth Outcomes After Antenatal Coronavirus Disease 2019 (COVID-19) Vaccination.

OBJECTIVE: To evaluate the association between antenatal messenger RNA (mRNA) coronavirus disease 2019 (COVID-19) vaccination and risk of adverse pregnancy outcomes. METHODS: This was a retrospective cohort study of individuals with singleton pregnancies with live deliveries between June 1, 2021, and January 31, 2022, with data available from eight integrated health care systems in the Vaccine Safety Datalink. Vaccine exposure was defined as receipt of one or two mRNA COVID-19 vaccine doses (primary series) during pregnancy. Outcomes were preterm birth (PTB) before 37 weeks of gestation, small-for-gestational age (SGA) neonates, gestational diabetes mellitus (GDM), gestational hypertension, and preeclampsia-eclampsia-HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome. Outcomes in individuals vaccinated were compared with those in propensity-matched individuals with unexposed pregnancies. Adjusted hazard ratios (aHRs) and 95% CIs were estimated for PTB and SGA using a time-dependent covariate Cox model, and adjusted relative risks (aRRs) were estimated for GDM, gestational hypertension, and preeclampsia-eclampsia-HELLP syndrome using Poisson regression with robust variance. RESULTS: Among 55,591 individuals eligible for inclusion, 23,517 (42.3%) received one or two mRNA COVID-19 vaccine doses during pregnancy. Receipt of mRNA COVID-19 vaccination varied by maternal age, race, Hispanic ethnicity, and history of COVID-19. Compared with no vaccination, mRNA COVID-19 vaccination was associated with a decreased risk of PTB (rate: 6.4 [vaccinated] vs 7.7 [unvaccinated] per 100, aHR 0.89; 95% CI, 0.83-0.94). Messenger RNA COVID-19 vaccination was not associated with SGA (8.3 vs 7.4 per 100; aHR 1.06, 95% CI, 0.99-1.13), GDM (11.9 vs 10.6 per 100; aRR 1.00, 95% CI, 0.90-1.10), gestational hypertension (10.8 vs 9.9 per 100; aRR 1.08, 95% CI, 0.96-1.22), or preeclampsia-eclampsia-HELLP syndrome (8.9 vs 8.4 per 100; aRR 1.10, 95% CI, 0.97-1.24). CONCLUSION: Receipt of an mRNA COVID-19 vaccine during pregnancy was not associated with an increased risk of adverse pregnancy outcomes; this information will be helpful for patients and clinicians when considering COVID-19 vaccination in pregnancy.

Acute health care utilization in the first 24 months postpartum by rurality and pregnancy complications: A prospective cohort study.

OBJECTIVE: To estimate the rate of acute health care use (hospitalizations and emergency department [ED] visits) among postpartum persons by rurality of residence and pregnancy complications. DATA SOURCES AND STUDY SETTING: 2006-2021 data from the Maine Health Data Organization's All Payer Claims Data. STUDY DESIGN: We estimated the rates of hospitalizations and ED visits during the first 24 months postpartum, separately, overall and by four-level rurality of residence (urban, large rural, small rural, and isolated rural) and by pregnancy complications (prenatal depression, hypertensive disorders of pregnancy [HDP], and gestational diabetes mellitus [GDM]). We used Poisson regression models, adjusting for potential confounders. Data were weighted to account for censoring before 24 months postpartum. DATA EXTRACTION METHODS: Deliveries during 2007-2019 (n = 122,412). PRINCIPAL FINDINGS: Approximately 4% of persons had at least one hospitalization within 24 months postpartum (mean monthly rate per 100 deliveries = 0.35). Adjusted rates were not different by rurality. Persons with prenatal depression (adjusted rate ratio [aRR] = 1.9; 95% confidence interval [CI] 1.5-2.5), HDP (aRR = 1.4; 1.0-2.0), and GDM (aRR = 1.4; 0.9-2.0) had higher hospitalization rates than those without these conditions. Approximately 44% of persons had at least one ED visit within 24 months postpartum (mean monthly rate per 100 deliveries = 5.4). Adjusted ED rates were higher for persons living in small rural areas as compared with urban areas (aRR = 1.3; 1.2-1.4). Persons with prenatal depression (aRR = 1.8; 1.7-1.9), HDP (aRR = 1.1; 1.0-1.2), and GDM (aRR = 1.3; 1.2-1.4) had higher ED rates than those without these conditions; ED rates were highest among those living in small rural areas. CONCLUSION: New policies and care practices may be needed to prevent acute health care encounters in the first 24 months after delivery for persons with common pregnancy conditions. Efforts to identify why postpartum people living in small rural areas have higher rates of ED visits are warranted.

Continuous non-invasive hemodynamic monitoring in early onset severe preeclampsia.

OBJECTIVES: Continuous hemodynamic monitoring offers the opportunity to individualize management in severe preeclampsia (PEC). We compared cardiac output (CO) and total peripheral resistance (TPR) measured by bioreactance (NICOM), Clearsite™ Fingercuff [CS), and 3D-echocardiography (3DE). STUDY DESIGN: This prospective observational study included 12 pregnant patients with early PEC. CO and TPR were measured simultaneously by NICOM, CS, and 3DE antepartum and 1-2 days postpartum. Using 3DE as the standard, CS and NICOM interchangeability, precision, accuracy, and correlation were assessed. RESULTS: Compared to 3DE-CO, CS-CO was highly correlated (R2 = 0.70, p = <0.0001) with low percentage error (PE 29%) which met criteria for interchangeablity. CS-TPR had strong correlation (R2 = 0.81, p = <0.0001) and low PE (29%). While CS tended to slightly overestimate CO (bias + 2.05 ±1.18 L/min, limit of agreement (LOA) -0.20 to 4.31) and underestimate TPR (bias -279 ±156 dyes/sec/cm5; LOA -580 to 18.4) these differences were unlikely to be clinically significant. Thus CS could be interchangeable with 3DE for CO and TPR. NICOM-CO had only moderate correlation with 3DE-CO (R2 = 0.29, p = 0.01) with high PE (52%) above threshold for interchangeability. NICOM-CO had low mean bias (-1.2 ±1.68 L/min) but wide 95% LOA (-4.41 to 2.14) suggesting adequate accuracy but low precision in relation to 3DE-CO. NICOM-TPR had poor correlation with 3DE-TPR (R2 = 0.32, p = 0.001) with high PE (67%), relatively low mean bias (238 ±256), and wide 95% LOA (-655 to 1131). NICOM did not meet the criteria for interchangeable with 3DE for CO and TPR. CONCLUSIONS: Clearsite Fingercuff, but not NICOM, has potential to be clinically useful for CO and TPR monitoring in severe preeclampsia.

Using a Patient Educational Video to Improve Knowledge of Maternal Mortality Warning Signs: A Randomized Controlled Trial.

OBJECTIVE: To determine whether a community-informed, language-concordant postpartum video education campaign, developed with community input, improves patients' knowledge of warning signs for postpartum maternal mortality (infection, hemorrhage, hypertensive disorders, and postpartum depression) compared with routine discharge procedures. METHODS: A single-center, investigator-blinded, parallel-group randomized controlled trial of postpartum individuals who delivered at a large, urban, tertiary care hospital. Eligible participants were enrolled and completed a baseline knowledge questionnaire. After delivery, they were randomized to routine discharge education (control) or routine education plus video education (intervention). After discharge education, patient knowledge was again assessed in both groups before participants left the hospital. The primary outcome was the percentage of participants who showed improvement in their knowledge, measured by the number of correct questionnaire responses after education compared with their baseline, assessed as a binary outcome. A sample size of 150 (75 per group) was planned to detect a 25% absolute increase in the frequency of the primary outcome. RESULTS: From July to August 2022, 296 participants were screened and 200 were randomized (100 per group). Eighty-two percent of participants had college or graduate education, and 71.5% had commercial insurance. There was no significant difference in baseline characteristics. There was no statistically significant difference in the percentage of participants who improved their scores between the baseline and posteducation questionnaires (64.5% vs 50.0%, P =.09). However, the median posteducation questionnaire total score was significantly higher in the video education group (14 [interquartile range 12-15] vs 13 [interquartile range 12-14], P =.003). In addition, they more frequently reported that video education was "very helpful" (83.9% vs 72.5%, P =.23) and that they were "very satisfied" with their education (86.1% vs 75.5%, P =.29). CONCLUSION: Enhanced postpartum education through a novel video did not result in a statistically significant difference in frequency of improved score on the posteducation questionnaires but was associated with increased satisfaction with care. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT05159726.

Medically Attended Acute Adverse Events in Pregnant People After Coronavirus Disease 2019 (COVID-19) Booster Vaccination.

In this multisite, observational, matched cohort study of more than 80,000 pregnant people, receipt of an mRNA monovalent coronavirus disease 2019 (COVID-19) booster vaccination in pregnancy was not associated with increased risk for thrombocytopenia, myocarditis, venous thromboembolism, ischemic stroke, or other serious adverse events within 21 or 42 days after booster vaccination. The mRNA monovalent COVID-19 booster in pregnancy was associated with an increased risk for medically attended malaise or fatigue within 7 days of vaccination (adjusted rate ratio [aRR] 3.64, 95% CI 2.42-5.48) and lymphadenopathy or lymphadenitis within 21 days (aRR 3.25, 95% CI 1.67-6.30) or 42 days (aRR 2.18, 95% CI 1.33-3.58) of vaccination. Our findings are consistent with prior evaluations of the primary COVID-19 vaccine series and are reassuring with respect to COVID-19 booster vaccination in pregnancy.

COVID-19 Booster Vaccination in Early Pregnancy and Surveillance for Spontaneous Abortion.

Importance: Adherence to COVID-19 booster vaccine recommendations has lagged in pregnant and nonpregnant adult populations. One barrier to booster vaccination is uncertainty regarding the safety of booster doses among pregnant people. Objective: To evaluate whether there is an association between COVID-19 booster vaccination during pregnancy and spontaneous abortion. Design, Setting, and Participants: This observational, case-control, surveillance study evaluated people aged 16 to 49 years with pregnancies at 6 to 19 weeks' gestation at 8 health systems in the Vaccine Safety Datalink from November 1, 2021, to June 12, 2022. Spontaneous abortion cases and ongoing pregnancy controls were evaluated during consecutive surveillance periods, defined by calendar time. Exposure: Primary exposure was receipt of a third messenger RNA (mRNA) COVID-19 vaccine dose within 28 days before spontaneous abortion or index date (midpoint of surveillance period in ongoing pregnancy controls). Secondary exposures were third mRNA vaccine doses in a 42-day window or any COVID-19 booster in 28- and 42-day windows. Main Outcomes and Measures: Spontaneous abortion cases and ongoing pregnancy controls were identified from electronic health data using a validated algorithm. Cases were assigned to a single surveillance period based on pregnancy outcome date. Eligible ongoing pregnancy time was assigned to 1 or more surveillance periods as an ongoing pregnancy-period control. Generalized estimating equations were used to estimate adjusted odds ratios (AOR) with gestational age, maternal age, antenatal visits, race and ethnicity, site, and surveillance period as covariates and robust variance estimates to account for inclusion of multiple pregnancy periods per unique pregnancy. Results: Among 112 718 unique pregnancies included in the study, the mean (SD) maternal age was 30.6 (5.5) years. Pregnant individuals were Asian, non-Hispanic (15.1%); Black, non-Hispanic (7.5%); Hispanic (35.6%); White, non-Hispanic (31.2%); and of other or unknown (10.6%); and 100% were female. Across eight 28-day surveillance periods, among 270 853 ongoing pregnancy-period controls, 11 095 (4.1%) had received a third mRNA COVID-19 vaccine in a 28-day window; among 14 226 cases, 553 (3.9%) had received a third mRNA COVID-19 vaccine within 28 days of the spontaneous abortion. Receipt of a third mRNA COVID-19 vaccine was not associated with spontaneous abortion in a 28-day window (AOR, 0.94; 95% CI, 0.86-1.03). Results were consistent when using a 42-day window (AOR, 0.97; 95% CI, 0.90-1.05) and for any COVID-19 booster in a 28-day (AOR, 0.94; 95% CI, 0.86-1.02) or 42-day (AOR, 0.96; 95% CI, 0.89-1.04) exposure window. Conclusions and Relevance: In this case-control surveillance study, COVID-19 booster vaccination in pregnancy was not associated with spontaneous abortion. These findings support the safety of recommendations for COVID-19 booster vaccination, including in pregnant populations.

Mental Health Within 24 Months After Delivery Among Women with Common Pregnancy Conditions.

Objective: The aim of this study is to estimate the risk of a new mental health diagnosis within the first 24 months postpartum among women with common pregnancy conditions, overall and by rurality. Materials and Methods: This longitudinal population-based study used the Maine Health Data Organization's All-Payer Claims Data to estimate the cumulative risk of a new mental health disorder diagnosis in the first 24 months postpartum among women with deliveries during 2007-2019 and who did not have a mental health diagnosis before pregnancy. Cox models were used to estimate hazard ratios for common pregnancy conditions (prenatal depression, gestational diabetes [GDM], and hypertensive disorders of pregnancy [HDP]) on the new diagnosis of five mental health conditions, separately. Models were adjusted for maternal demographics and pregnancy characteristics. Results: Of the 123,125 deliveries, the cumulative risk of being diagnosed in the first 24 months postpartum with depression was 28%, anxiety 25%, bipolar disorder 3%, post-traumatic stress disorder 6%, and schizophrenia/psychotic disorder 1%. Women with prenatal depression were at higher risk of having a postpartum mental health diagnosis compared with women without prenatal depression (adjusted hazard ratios [aHRs] ranged from 2.5 [for anxiety] to 4.1 [for postpartum depression]). Risk of having postpartum depression was modestly higher among women with HDP, as was the risk of postpartum bipolar disorder among those with GDM. Findings were generally similar between women living in rural versus urban areas. Conclusions: Effective interventions to prevent, screen, and treat mental health conditions among women with pregnancy complications for an extended time postpartum are warranted.

Provision of Postpartum Contraception Before and After the Start of the COVID-19 Pandemic in Maine.

OBJECTIVE: Preliminary findings from selected health systems revealed interruptions in reproductive health care services due to the COVID-19 pandemic. We estimated changes in postpartum contraceptive provision associated with the start of the COVID-19 pandemic in Maine. METHODS: We used the Maine Health Data Organization's All Payer Claims Database for deliveries from October 2015 through March 2021 (n = 45 916). Using an interrupted time-series analysis design, we estimated changes in provision rates of long-acting reversible contraception (LARC), permanent contraception, and moderately effective contraception within 3 and 60 days of delivery after the start of the COVID-19 pandemic. We performed 6- and 12-month analyses (April 2020-September 2020, April 2020-March 2021) as compared with the reference period (October 2015-March 2020). We used Poisson regression models to calculate level-change rate ratios (RRs) and 95% CIs. RESULTS: The 6-month analysis found that provision of LARC (RR = 1.89; 95% CI, 1.76-2.02) and moderately effective contraception (RR = 1.51; 95% CI, 1.33-1.72) within 3 days of delivery increased at the start of the COVID-19 pandemic, while provision of LARC (RR = 0.95; 95% CI, 0.93-0.97) and moderately effective contraception (RR = 1.08; 95% CI, 1.05-1.11) within 60 days of delivery was stable. Rates of provision of permanent contraception within 3 days (RR = 0.70; 95% CI, 0.63-0.78) and 60 days (RR = 0.71; 95% CI, 0.63-0.80) decreased. RRs from the 12-month analysis were generally attenuated. CONCLUSION: Disruptions in postpartum provision of permanent contraception occurred at the beginning of the COVID-19 pandemic in Maine. Public health policies should include guidance for contraceptive provision during public health emergencies and consider designating permanent contraception as a nonelective procedure.

Tdap vaccination during pregnancy and risk of chorioamnionitis and related infant outcomes.

INTRODUCTION: An increased risk of chorioamnionitis in people receiving tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine during pregnancy has been reported. The importance of this association is unclear as additional study has not demonstrated increased adverse infant outcomes associated with Tdap vaccination in pregnancy. METHODS: We conducted a retrospective observational cohort study of pregnant people ages 15-49 years with singleton pregnancies ending in live birth who were members of 8 Vaccine Safety Datalink (VSD) sites during October 2016-September 2018. We used a time-dependent covariate Cox model with stabilized inverse probability weights applied to evaluate associations between Tdap vaccination during pregnancy and chorioamnionitis and preterm birth outcomes. We used Poisson regression with robust variance with stabilized inverse probability weights applied to evaluate the association of Tdap vaccination with adverse infant outcomes. We performed medical record reviews on a random sample of patients with ICD-10-CM-diagnosed chorioamnionitis to determine positive predictive values (PPV) of coded chorioamnionitisfor "probable clinical chorioamnionitis," "possible clinical chorioamnionitis," or "histologic chorioamnionitis." RESULTS: We included 118,211 pregnant people; 103,258 (87%) received Tdap vaccine during pregnancy; 8098 (7%) were diagnosed with chorioamnionitis. The adjusted hazard ratio for chorioamnionitis in the Tdap vaccine-exposed group compared to unexposed was 0.96 (95% CI 0.90-1.03). There was no association between Tdap vaccine and preterm birth or adverse infant outcomes associated with chorioamnionitis. Chart reviews were performed for 528 pregnant people with chorioamnionitis. The PPV for clinical (probable or possible clinical chorioamnionitis) was 48% and 59% for histologic chorioamnionitis. The PPV for the combined outcome of clinical or histologic chorioamnionitis was 81%. CONCLUSIONS AND RELEVANCE: Tdap vaccine exposure during pregnancy was not associated with chorioamnionitis, preterm birth, or adverse infant outcomes. ICD-10 codes for chorioamnionitis lack specificity for clinical chorioamnionitis and should be a recognized limitation when interpreting results.

Association between hypertensive disorders of pregnancy and cardiovascular diseases within 24 months after delivery.

BACKGROUND: Despite the well-known association between hypertensive disorders of pregnancy and cardiovascular diseases, there are limited data on which specific cardiovascular diagnoses have the greatest risk profiles during the first 24 months after delivery. Most existing data on hypertensive disorders of pregnancy and short-term cardiovascular disease risks are limited to the immediate postpartum period; however, it is crucial to determine cardiovascular disease risk up to 24 months after delivery to inform cardiovascular disease screening protocols during the extended postpartum period. OBJECTIVE: This study aimed to delineate the risk of cardiovascular diagnoses in the first 24 months after delivery among patients with hypertensive disorders of pregnancy compared with patients without hypertensive disorders of pregnancy. STUDY DESIGN: This longitudinal population-based study included pregnant individuals with deliveries during 2007 to 2019 in the Maine Health Data Organization's All Payer Claims Data. This study excluded patients with preexisting cardiovascular disease, with multifetal pregnancies, or without continuous insurance during pregnancy. Hypertensive disorders of pregnancy and cardiovascular diseases (categorized by specific conditions: heart failure, ischemic heart disease, arrhythmia or cardiac arrest, cardiomyopathy, cerebrovascular disease or stroke, and new chronic hypertension) were identified using International Classification of Diseases, Ninth Revision, and International Classification of Diseases, Tenth Revision, diagnosis codes. Cox proportional hazards models were used to estimate hazard ratios, adjusting for potential confounding factors. RESULTS: Of the 119,422 pregnancies examined, the cumulative risk of cardiovascular disease within 24 months after delivery for those with hypertensive disorders of pregnancy vs those without hypertensive disorders of pregnancy was 0.6% vs 0.2% for heart failure, 0.3% vs 0.1% for ischemic heart disease, 0.2% vs 0.2% for arrhythmia or cardiac arrest, 0.6% vs 0.2% for cardiomyopathy, 0.8% vs 0.4% for cerebrovascular disease or stroke, 1.6% vs 0.7% for severe cardiac disease (composite outcome of heart failure, cerebrovascular disease or stroke, or cardiomyopathy), and 9.7% vs 1.5% for new chronic hypertension. After adjustment for potential confounders, those with hypertensive disorders of pregnancy had an increased risk of heart failure, cerebrovascular disease, cardiomyopathy, and severe cardiac disease within the first 24 months after delivery (adjusted hazard ratio, 2.81 [95% confidence interval, 1.90-4.15], 1.43 [95% confidence interval, 1.07-1.91], 2.90 [95% confidence interval, 1.96-4.27], and 1.90 [95% confidence interval, 1.54-2.30], respectively) compared with those without hypertensive disorders of pregnancy. In addition, those with hypertensive disorders of pregnancy had an increased risk for new chronic hypertension diagnosed after 42 days after delivery (adjusted hazard ratio, 7.29; 95% confidence interval, 6.57-8.09). There was no association between hypertensive disorders of pregnancy and ischemic heart disease (adjusted hazard ratio, 0.92; 95% confidence interval, 0.55-1.54) or cardiac arrest or arrhythmia (adjusted hazard ratio, 0.90; 95% confidence interval, 0.52-1.57). In addition, among women with hypertensive disorders of pregnancy, the highest proportion of first cardiovascular disease diagnoses occurred during the first month after delivery for cardiomyopathy (44%), heart failure (39%), cerebrovascular disease or stroke (39%), and severe cardiac disease (41%). CONCLUSION: Patients with hypertensive disorders of pregnancy had an increased risk of developing new chronic hypertension, heart failure, cerebrovascular disease, and cardiomyopathy within 24 months after delivery. There was no association between hypertensive disorders of pregnancy and ischemic heart disease or cardiac arrest or arrhythmia. Patients with hypertensive disorders of pregnancy need targeted early postpartum interventions and increased monitoring in the first 24 months after delivery. This may preserve long-term health and improve maternal and neonatal outcomes in a subsequent pregnancy.

Association of Prenatal Depression With New Cardiovascular Disease Within 24 Months Postpartum.

Background Although depression is well established as an independent risk factor for cardiovascular disease (CVD) in the nonpregnant population, this association has largely not been investigated in pregnant populations. We aimed to estimate the cumulative risk of new CVD in the first 24 months postpartum among pregnant individuals diagnosed with prenatal depression compared with patients without depression diagnosed during pregnancy. Methods and Results Our longitudinal population-based study included pregnant individuals with deliveries during 2007 to 2019 in the Maine Health Data Organization's All Payer Claims Data. We excluded those with prepregnancy CVD, multifetal gestations, or no continuous health insurance during pregnancy. Prenatal depression and CVD (heart failure, ischemic heart disease, arrhythmia/cardiac arrest, cardiomyopathy, cerebrovascular disease, and chronic hypertension) were identified by International Classification of Diseases, Ninth Revision (ICD-9)/International Classification of Diseases, Tenth Revision (ICD-10) codes. Cox models were used to estimate hazard ratios (HRs), adjusting for potential confounding factors. Analyses were stratified by hypertensive disorder of pregnancy. A total of 119 422 pregnancies were examined. Pregnant individuals with prenatal depression had an increased risk of ischemic heart disease, arrhythmia/cardiac arrest, cardiomyopathy, and new hypertension (adjusted HR [aHR], 1.83 [95% CI, 1.20-2.80], aHR, 1.60 [95% CI, 1.10-2.31], aHR, 1.61 [95% CI, 1.15-2.24], and aHR, 1.32 [95% CI, 1.17-1.50], respectively). When the analyses were stratified by co-occurring hypertensive disorders of pregnancy, several of these associations persisted. Conclusions The cumulative risk of a new CVD diagnosis postpartum was elevated among individuals with prenatal depression and persists even in the absence of co-occurring hypertensive disorders of pregnancy. Further research to determine the causal pathway can inform postpartum CVD preventive measures.

Dyslipidemia and Risk of Preeclampsia: A Multiancestry Mendelian Randomization Study.

BACKGROUND: Preeclampsia is a leading cause of maternal morbidity, and dyslipidemia has been associated with preeclampsia in observational studies. We use Mendelian randomization analyses to estimate the association between lipid levels, their pharmacological targets, and the risk of preeclampsia in 4 ancestry groups. METHODS: We extracted uncorrelated (R2<0.001) single-nucleotide polymorphisms strongly associated (P<5×10-8) with LDL-C (low-density lipoprotein cholesterol), HDL-C (high-density lipoprotein cholesterol), and triglycerides from genome-wide association studies of European, admixed African, Latino, and East Asian ancestry participants. Genetic associations with risk of preeclampsia were extracted from studies of the same ancestry groups. Inverse-variance weighted analyses were performed separately for each ancestry group before they were meta-analyzed. Sensitivity analyses were conducted to evaluate bias due to genetic pleiotropy, demography, and indirect genetic effects. RESULTS: The meta-analysis across 4 ancestry groups included 1.5 million subjects with lipid measurements, 7425 subjects with preeclampsia, and 239 290 without preeclampsia. Increasing HDL-C was associated with reduced risk of preeclampsia (odds ratio, 0.84 [95% CI, 0.74-0.94]; P=0.004; per SD increase in HDL-C), which was consistent across sensitivity analyses. We also observed cholesteryl ester transfer protein inhibition-a drug target that increases HDL-C-may have a protective effect. We observed no consistent effect of LDL-C or triglycerides on the risk of preeclampsia. CONCLUSIONS: We observed a protective effect of elevated HDL-C on risk of preeclampsia. Our findings align with the lack of effect in trials of LDL-C modifying drugs but suggest that HDL-C may be a new target for screening and intervention.

COVID-19 Vaccine Safety Surveillance in Early Pregnancy in the United States: Design Factors Affecting the Association Between Vaccine and Spontaneous Abortion.

In the Vaccine Safety Datalink (VSD), we previously reported no association between coronavirus disease 2019 (COVID-19) vaccination in early pregnancy and spontaneous abortion (SAB). The present study aims to understand how time since vaccine rollout or other methodological factors could affect results. Using a case-control design and generalized estimating equations, we estimated the odds ratios (ORs) of COVID-19 vaccination in the 28 days before a SAB or last date of the surveillance period (index date) in ongoing pregnancies and occurrence of SAB, across cumulative 4-week periods from December 2020 through June 2021. Using data from a single site, we evaluated alternative methodological approaches: increasing the exposure window to 42 days, modifying the index date from the last day to the midpoint of the surveillance period, and constructing a cohort design with a time-dependent exposure model. A protective effect (OR = 0.78, 95% confidence interval: 0.69, 0.89), observed with 3-cumulative periods ending March 8, 2021, was attenuated when surveillance extended to June 28, 2021 (OR = 1.02, 95% confidence interval: 0.96, 1.08). We observed a lower OR for a 42-day window compared with a 28-day window. The time-dependent model showed no association. Timing of the surveillance appears to be an important factor affecting the observed vaccine-SAB association.