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.

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 (GDM) is associated with an overall lifetime increased risk of cardiometabolic disease, even among those without intercurrent type 2 diabetes. However, the association between GDM and short-term risk of cardiovascular disease (CVD) is unclear. Establishing short-term risks of CVD for patients with GDM has significant potential to inform early screening and targeted intervention strategies to reduce premature cardiovascular morbidity among women. OBJECTIVE: We aimed to estimate the risk of cardiovascular disease diagnoses in the first 24 months postpartum among patients with GDM compared with patients without GDM. STUDY DESIGN: Our longitudinal population-based study included pregnant individuals with deliveries during 2007-2019 in the Maine Health Data Organization's All Payer Claims Data. We excluded records with gestational age <20 weeks and deliveries with non-Maine residence, multifetal gestation, those without insurance in the month of delivery or the 3 months before pregnancy, those with implausible time to next pregnancy (<60 days), pre-gestational diabetes mellitus, and any pre-pregnancy diagnosis of the cardiovascular conditions being examined postpartum. GDM and CVD (heart failure, ischemic heart disease, arrhythmia/cardiac arrest, cardiomyopathy, cerebrovascular disease/stroke, and new chronic hypertension) were identified by ICD 9/10 diagnosis codes. Cox proportional hazards models were used to estimate hazard ratios (HR), adjusting for potential confounding factors. We assessed whether the association between GDM and chronic hypertension was mediated by intercurrent diabetes mellitus. RESULTS: Of the 84,746 pregnancies examined, the cumulative risk of CVD within 24 months postpartum for those with GDM vs. without GDM 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 GDM have an increased risk of new chronic hypertension (adjusted hazard ratio (aHR) 1.56 (95% CI 1.32-1.86)) within the first 24 months postpartum as compared to those without GDM. There was no association between GDM and ischemic heart disease (aHR 0.75 (95% CI 0.34-1.65)), cerebrovascular disease/stroke (aHR 1.13 (95% CI 0.78-1.66)), arrhythmia/cardiac arrest (aHR 1.16 (95% CI 0.59-2.29)), or cardiomyopathy (aHR 0.75 (95% CI 0.40-1.41)) within the first 24 months postpartum. Those with GDM appeared to have a decreased risk of heart failure within 24 months postpartum, aHR 0.45 (95% CI (0.21-0.98)). Our mediation analyses estimated that 28% of the effect of GDM on new chronic hypertension was mediated through intercurrent diabetes mellitus. CONCLUSION: Patients with GDM have a significantly increased risk of new chronic hypertension as early as 24 months postpartum. The majority of this effect was not due to the development of diabetes mellitus. Our findings suggest that all women with GDM need careful monitoring and screening for new chronic hypertension in the first 2 years postpartum.

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.

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.

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.

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.

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.

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.

Severe Maternal Morbidity Review and Preventability Assessment in a Large Academic Center.

With the goal of identifying factors contributing to severe maternal morbidity (SMM) at our institution, we established a formal SMM review process. We performed a retrospective cohort study including all SMM cases as defined by American College of Obstetricians and Gynecologists and Society for Maternal-Fetal Medicine consensus criteria that were managed at Yale-New Haven Hospital over a 4-year period. Overall, 156 cases were reviewed. The SMM rate was 0.49% (95% CI 0.40-0.58). The leading causes of SMM were hemorrhage (44.9%) and nonintrauterine infection (14.1%). Two thirds of the cases were deemed to be preventable. Preventability was mostly associated with health care professional-level (79.4%) and system-level (58.8%) factors that could coexist. Detailed case review allowed for identification of preventable causes of SMM, revealed gaps in care, and allowed for implementation of practice changes targeting health care professional-level and system-level factors.

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.

Rural-urban residence and sequelae of hypertensive disorders of pregnancy in the first year postpartum, 2007 - 2019.

OBJECTIVES: To estimate the association between rural residence and sequelae of hypertensive disorders of pregnancy (HDP) in the first year postpartum. STUDY DESIGN: We used the Maine Health Data Organization's All Payer Claims Data to identify women with HDP who delivered during 2007-2019 and did not have chronic hypertension or pre-pregnancy cardiac conditions (n = 8882). We used Cox proportional hazards modeling to estimate rural-urban hazard ratios (HR) and 95% confidence intervals (CI), adjusting for HDP subtype, age, insurance, nulliparity, and co-morbidities. Results were stratified by HDP subtype and timing of acute care visits. MAIN OUTCOME MEASURES: Risk of at least one emergency room or inpatient visit related to hypertension or cardiovascular conditions in the first year postpartum and receipt of outpatient antihypertensive medications from 4 days to 1 year postpartum, separately. RESULTS: Overall, risk of at least one acute care visit in the first year postpartum was not different between rural vs urban women (4.2% vs 4.2%; adjusted HR 0.98; 95% CI 0.79,1.21), and outpatient receipt of antihypertensive medication was not different (12.9% vs 12.8%; adjusted HR 0.99; 95% CI 0.87, 1.12). However, stratified analyses suggested some differences (e.g. preeclampsia with severe features: acute care visit adjusted HR 1.54; 95% CI 0.95, 2.49). CONCLUSIONS: Rural and urban women do not differ in the risks of these common HDP sequelae, though rural women may have increased risk by HDP subtype or timing of acute care visit. Future research should investigate postpartum interventions for reducing HDP sequelae in rural and urban women.

Use of family history of cardiovascular disease or chronic hypertension to better identify who needs postpartum cardiovascular risk screening.

BACKGROUND: Individuals with pregnancies complicated by hypertensive disorders of pregnancy are at increased risk of cardiovascular disease. However, not all who have hypertensive disorders of pregnancy are at risk, and not all who have uncomplicated pregnancies are without risk. OBJECTIVE: This study aimed to determine if use of first-degree family history of cardiovascular disease or chronic hypertension better identifies individuals who need postpartum cardiovascular risk screening. STUDY DESIGN: Participants were included if they had pregnancies complicated by hypertensive disorders of pregnancy or uncomplicated, term pregnancies. Individuals with a first-degree relative with chronic hypertension, myocardial infarction, or stroke were deemed to have a positive family history and were thus included. RESULTS: Four groups were considered: 302 individuals with hypertensive disorders of pregnancy who had a positive family history, 218 individuals with hypertensive disorders of pregnancy with no family history, 39 control individuals with a positive family history, and 63 control individuals with no family history. Among individuals with hypertensive disorders of pregnancy, those with a positive family history were more likely to be diagnosed with chronic hypertension, and to have elevated 30-year lipid, 30-year body mass index, and lifetime cardiovascular disease risk score (all P<.05). Among individuals with uncomplicated pregnancies, those with a positive family history were more likely to be diagnosed with chronic hypertension (P<.05) and meet criteria for metabolic syndrome (P<.05). CONCLUSION: First-degree family history of cardiovascular disease and/or chronic hypertension can be used to reliably identify individuals without pregnancy complications who should have postpartum cardiovascular risk screening, and may better determine which individuals who have a pregnancy complicated by hypertensive disorders of pregnancy would most benefit from postpartum cardiovascular risk screening.

High-sensitivity C-reactive protein use in cardiovascular risk screening at 6 to 12 months postpartum following hypertensive disorders of pregnancy.

BACKGROUND: Patients with a hypertensive disorder of pregnancy are more likely to have underlying cardiovascular risk factors and are at increased risk of future cardiovascular disease. These patients are more likely to be diagnosed with new-onset chronic hypertension and meet the criteria for metabolic syndrome postpartum. High-sensitivity C-reactive protein is a marker of general inflammation and may be used to identify increased risk for cardiovascular disease. OBJECTIVE: This collaborative data-sharing study between Yale University, United States (Yale Hearts Moms study) and Queen's University, Canada (Maternal Health Clinic) aimed to study the utility of high-sensitivity C-reactive protein in postpartum cardiovascular risk screening, as determined by 30-year risk (Framingham) and metabolic syndrome 6 to 12 months postpartum. STUDY DESIGN: Patients with a hypertensive disorder of pregnancy (n=478) or an uncomplicated, term pregnancy (n=90) had cardiovascular risk screening and risk scoring performed at 6 to 12 months postpartum. Patients were excluded if they had a multiple gestation or chronic hypertension, diabetes mellitus, or cardiovascular disease diagnosed before pregnancy. Patients were categorized according to high-sensitivity C-reactive protein (mg/L) into Normal (<3.0), High (3.1 to <10.0), and Acute (≥10.0) groups. The primary outcome of the study was risk for future cardiovascular events, calculated through surrogate measures such as hypertension and cholesterol. Kruskal-Wallis and chi-square tests were used to compare groups, with post hoc tests corrected using the Bonferroni method. Multivariable logistic regression was used to assess the association between high-sensitivity C-reactive protein and cardiovascular risk, adjusting for relevant medical and sociodemographic variables. Analysis was completed with IBM SPSS Statistics, version 27. RESULTS: Patients in the High and Acute high-sensitivity C-reactive protein groups were more likely to have a body mass index ≥30, to have experienced a hypertensive disorder of pregnancy, to have a lower household income, and to have not breastfed or to have breastfed for <6 months, when compared with the Normal high-sensitivity C-reactive protein group (all P<.05). Patients in the High and Acute high-sensitivity C-reactive protein groups had higher 30-year cardiovascular risk scores and were more likely to have metabolic syndrome when compared with the Normal high-sensitivity C-reactive protein group (all P<.05). Patients with High high-sensitivity C-reactive protein had 2-fold odds of metabolic syndrome 6 to 12 months after delivery, compared with those in the Normal high-sensitivity C-reactive protein group (adjusted odds ratio, 2.85 [95% confidence interval, 1.66-4.91]), adjusting for hypertensive disorder of pregnancy, body mass index, clinic site, breastfeeding, income, and family history of cardiovascular disease. Those with Acute high-sensitivity C-reactive protein also seemed to have elevated odds of metabolic syndrome compared with the Normal high-sensitivity C-reactive protein group (adjusted odds ratio, 2.52 [95% confidence interval, 1.24-5.12]). The odds of chronic hypertension were significantly higher (P<.05) in the High high-sensitivity C-reactive protein group (adjusted odds ratio, 1.72 [95% confidence interval, 1.12-2.65]) compared with the Normal group. CONCLUSION: Individuals with elevated postpartum high-sensitivity C-reactive protein are at increased risk of cardiovascular disease 6 to 12 months postpartum after a pregnancy complicated by a hypertensive disorder of pregnancy. Future research is critical to determine the most comprehensive and accurate method and timing of postpartum cardiovascular risk screening to decrease the incidence of preventable cardiovascular mortality among women.

Acute pain pathways: protocol for a prospective cohort study.

INTRODUCTION: Opioid analgesics are often used to treat moderate-to-severe acute non-cancer pain; however, there is little high-quality evidence to guide clinician prescribing. An essential element to developing evidence-based guidelines is a better understanding of pain management and pain control among individuals experiencing acute pain for various common diagnoses. METHODS AND ANALYSIS: This multicentre prospective observational study will recruit 1550 opioid-naïve participants with acute pain seen in diverse clinical settings including primary/urgent care, emergency departments and dental clinics. Participants will be followed for 6 months with the aid of a patient-centred health data aggregating platform that consolidates data from study questionnaires, electronic health record data on healthcare services received, prescription fill data from pharmacies, and activity and sleep data from a Fitbit activity tracker. Participants will be enrolled to represent diverse races and ethnicities and pain conditions, as well as geographical diversity. Data analysis will focus on assessing patients' patterns of pain and opioid analgesic use, along with other pain treatments; associations between patient and condition characteristics and patient-centred outcomes including resolution of pain, satisfaction with care and long-term use of opioid analgesics; and descriptive analyses of patient management of leftover opioids. ETHICS AND DISSEMINATION: This study has received approval from IRBs at each site. Results will be made available to participants, funders, the research community and the public. TRIAL REGISTRATION NUMBER: NCT04509115.