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.

Characterisation and validation of lactation information from structured electronic health records for use in pharmacoepidemiological studies.

BACKGROUND: Breastfeeding information stored within electronic health records (EHR) has recently been used for pharmacoepidemiological research, however the data are primarily collected for clinical care. OBJECTIVES: To characterise breastfeeding information recorded in structured fields in EHR during infant and postpartum health care visits, and to assess the validity of lactation status based on EHR data versus maternal report at research study visits. METHODS: We assessed breastfeeding information recorded in structured fields in EHR from one health system for a subset of 211 patients who were also enrolled in a study on breast milk composition between 2014 and 2017 that required participants to exclusively breastfeed their infants until at least 1 month of age. We assessed the frequency of breastfeeding information in EHR during the first 12 months of age and compared lactation status based on EHR with maternal report at 1 and 6-month study visits (reference standard). RESULTS: The median number of breastfeeding records in the EHR per infant was six (interquartile range 3) with most observations clustering in the first few weeks of life and around well-infant visits. At the 6-month study visit, 93.8% of participants were breastfeeding and 80.1% were exclusively breastfeeding according to maternal report. Sensitivity of EHR data for identifying ever breastfeeding was at or near 100%, and sensitivity for identifying ever exclusive breastfeeding was 98.0% (95% CI: 95.0%, 99.2%). Sensitivities were 97.3% (95% CI: 93.9%, 98.9%) for identifying any breastfeeding and 94.4% (95% CI: 89.7%, 97.0%) for exclusive breastfeeding, and positive predictive values were 99.5% (95% CI: 97.0%, 99.9%) for any breastfeeding and 95.0% (95% CI: 90.4%, 97.4%) for exclusive breastfeeding. CONCLUSIONS: Breastfeeding information in structured EHR fields have the potential to accurately classify lactation status. The validity of these data should be assessed in populations with a lower breastfeeding prevalence.

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.

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.

The most common medications dispensed to lactating persons: An electronic health record-based approach.

PURPOSE: Using a novel, electronic health record (EHR)-based approach, to estimate the prevalence of prescription medication use at 2, 4, and 6 months postpartum among lactating individuals. METHODS: We utilized automated EHR data from a US health system that records infant feeding information at well-child visits. We linked mothers who received prenatal care to their infants born May 2018-June 2019, and we required infants to have ≥1 well-child visit between 31 and 90 days of life (i.e., 2-month well-child visit with a ±1 month window). Mothers were classified as lactating at the 2-month well-child visit if their infant received breast milk at the 2-month well-child visit. For subsequent well-child visits at 4 and 6 months, mothers were considered lactating if their infant was still receiving breast milk. RESULTS: We identified 6013 mothers meeting inclusion criteria, and 4158 (69.2%) were classified as lactating at the 2-month well-child visit. Among those classified as lactating, the most common medication classes dispensed around the 2-month well-child visit were oral progestin contraceptives (19.1%), selective serotonin reuptake inhibitors (8.8%), first generation cephalosporins (4.3%), thyroid hormones (3.5%), nonsteroidal anti-inflammatory agents (3.4%), penicillinase-resistant penicillins (3.1%), topical corticosteroids (2.9%), and oral imidazole-related antifungals (2.0%). The most common medication classes were similar around the 4 and 6-month well-child visits although prevalence estimates were often lower. CONCLUSIONS: Progestin-only contraceptives, antidepressants, and antibiotics were the most dispensed medications among lactating mothers. With routine collection of breastfeeding information, mother-infant linked EHR data may overcome limitations in previous studies of medication utilization during lactation. These data should be considered for studies of medication safety during lactation given the need for human safety data.

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.

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.

Influenza vaccination during pregnancy and risk of selected major structural congenital heart defects, National Birth Defects Prevention Study 2006-2011.

BACKGROUND: Although results from studies of first-trimester influenza vaccination and congenital heart defects (CHDs) have been reassuring, data are limited for specific CHDs. METHODS: We assessed associations between reported maternal influenza vaccination, 1 month before pregnancy (B1) through end of third pregnancy month (P3), and specific CHDs using data from a multisite, population-based case-control study. Analysis included 2,982 case children diagnosed with a simple CHD (no other cardiac involvement with or without extracardiac defects) and 4,937 control children without a birth defect with estimated delivery dates during 2006-2011. For defects with ≥5 exposed case children, we used logistic regression to estimate propensity score-adjusted odds ratios (aORs) and 95% confidence intervals (CIs), adjusting for estimated delivery year and season; plurality; and maternal age at delivery, race/ethnicity, low folate intake, and smoking and alcohol use during B1P3. RESULTS: Overall, 124 (4.2%) simple CHD case mothers and 197 (4.0%) control mothers reported influenza vaccination from 1 month before through the third pregnancy month. The aOR for any simple CHD was 0.97 (95% CI: 0.76-1.23). Adjusted ORs for specific simple CHDs ranged from 0.62 for hypoplastic left heart syndrome to 2.34 for total anomalous pulmonary venous return (TAPVR). All adjusted CIs included the null except for TAPVR. CONCLUSIONS: Although we cannot fully exclude that exposure misclassification may have masked risks for some CHDs, findings add to existing evidence supporting the safety of inactivated influenza vaccination during pregnancy. The TAPVR result may be due to chance, but it may help inform future studies.

Patterns in Prescription Opioids, Benzodiazepines, and Stimulants Filled by Pregnant Medicaid Beneficiaries.

This study analyzes patterns in prescriptions filled by pregnant Medicaid beneficiaries for opioids, benzodiazepines, and stimulants.

Maternal hepatitis C prevalence and trends by county, US: 2016-2020.

BACKGROUND: Trends in the prevalence of hepatitis C virus (HCV) infection among women delivering live births may differ in rural vs. urban areas of the United States, but estimation of trends based on observed counts may lead to unstable estimates in rural counties due to small numbers. OBJECTIVES: The objective of the study was to use small area estimation methods to provide updated county-level prevalence estimates and, for the first time, trends in maternal HCV infection among live births by county-level rurality. METHODS: Cross-sectional natality data from 2016 to 2020 were used to estimate maternal hepatitis C prevalence using hierarchical Bayesian models with spatiotemporal random effects to produce annual county-level estimates of maternal HCV infection and trends over time. Models included a 6-level rural-urban county classification, year, maternal characteristics and county-specific covariates. Data were analysed in 2022. RESULTS: There were 90,764/18,905,314 live births (4.8 per 1000) with HCV infection reported on the birth certificate. Hepatitis C prevalence was higher among rural counties as compared to urban counties. Rural counties had the largest annual increases in maternal hepatitis C prevalence (per 1000 births) from 2016 to 2020 (micropolitan: 0.39; noncore: 0.40), with smaller increases among less densely populated urban counties (medium metro: 0.28; small metro: 0.28) and urban counties (large central metro:0.11; large fringe metro: 0.14). CONCLUSIONS: The prevalence of maternal HCV infection was the highest in rural counties, and rural counties saw the greatest average prevalence increase during 2016-2020. County-level data can help in monitoring rural-urban trends in maternal HCV infection to reduce geographic disparities.

Antidepressant Fill and Dose Trajectories in Pregnant Women with Depression and/or Anxiety: A Norwegian Registry Linkage Study.

Background: Few studies investigated longitudinal antidepressant exposure during pregnancy and included dosage in the assessment. Methods: We conducted a nationwide, registry-linkage study in Norway using data on antidepressant prescription fills in pregnancies lasting ≥32 weeks in women with a delivery between 2009 and 2018 who had a depression/anxiety diagnosis and antidepressant fills prior to pregnancy. Information on antidepressant exposure by week (measured by filled prescriptions) and prescribed average daily dose was used in longitudinal k-means trajectory modelling for a 108-week time window from six months prior to pregnancy to one year after delivery. Factors associated with trajectory group membership were examined using multinomial logistic regression models. Results: We included 8,460 pregnancies in 8,092 women. Four antidepressant fill trajectories were identified based on filled antidepressant prescriptions: two distinct discontinuing patterns, one at around the start of pregnancy (30.4%) and one around the end of pregnancy (33.8%); one continuing pattern (20.6%); and one interrupting pattern (15.2%). Using average usual daily dose, we identified low dose discontinuing (60.3%), medium dose reducing (20.6%) and high dose continuing (15.2%) patterns. The multinomial logistic regressions showed that the fill trajectory group membership was strongly associated with: antidepressant type and dose prior to pregnancy and co-medication prior to pregnancy, maternal age, marital status, parity, previous pregnancy loss, and pregnancy planning. Conclusion: Longitudinal trajectory modelling revealed distinct antidepressant fill and dosage patterns in the period around pregnancy. Knowledge about factors associated with utilization trajectories might be useful for health-care personnel counselling women about antidepressant use in pregnancy.

Influenza vaccination during pregnancy and risk of selected major structural noncardiac birth defects, National Birth Defects Prevention Study 2006-2011.

PURPOSE: To assess associations between influenza vaccination during etiologically-relevant windows and selected major structural non-cardiac birth defects. STUDY DESIGN: We analyzed data from the National Birth Defects Prevention Study, a multisite, population-based case-control study, for 8233 case children diagnosed with a birth defect and 4937 control children without a birth defect with delivery dates during 2006-2011. For all analyses except for neural tube defects (NTDs), we classified mothers who reported influenza vaccination 1 month before through the third pregnancy month as exposed; the exposure window for NTDs was 1 month before through the first pregnancy month. For defects with five or more exposed case children, we used logistic regression to estimate propensity score-adjusted odds ratios (aORs) and 95% confidence intervals (CIs), adjusting for estimated delivery year and season; plurality; maternal age, race/ethnicity, smoking and alcohol use, low folate intake; and, for NTDs, folate antagonist medications. RESULTS: There were 334 (4.1%) case and 197 (4.0%) control mothers who reported influenza vaccination from 1 month before through the third pregnancy month. Adjusted ORs ranged from 0.53 for omphalocele to 1.74 for duodenal atresia/stenosis. Most aORs (11 of 19) were ≤1 and all adjusted CIs included the null. The unadjusted CIs for two defects, hypospadias and craniosynostosis, excluded the null. These estimates were attenuated upon covariate adjustment (hypospadias aOR: 1.25 (95% CI 0.89, 1.76); craniosynostosis aOR: 1.23 (95% CI: 0.88, 1.74)). CONCLUSIONS: Results for several non-cardiac major birth defects add to the existing evidence supporting the safety of inactivated influenza vaccination during pregnancy. Under-reporting of vaccination may have biased estimates downward.

Differences in the Association Between Oral Glucocorticoids and Risk of Preterm Birth by Data Source: Reconciling the Results.

OBJECTIVE: To investigate causes of discrepancies in the association between early pregnancy oral glucocorticoid (OGC) use and preterm birth risk among women with rheumatoid arthritis (RA) in health care utilization data from California Medicaid (Medi-Cal) and the prospective cohort MotherToBaby Pregnancy Studies. METHODS: Separately, we estimated risk ratios (RRs) between OGC exposure before gestational day 140 and preterm birth risk in data from Medi-Cal (2007-2013; n = 844) and MotherToBaby (2003-2014; n = 528). We explored differences in socioeconomic status, OGC dose distribution, exposure misclassification, and confounding by RA severity across the data sources. RESULTS: Preterm birth risk in women without OGC was 17.3% in Medi-Cal and was 9.7% in MotherToBaby. There was no association between OGC and preterm birth in Medi-Cal (adjusted RR 1.00 [95% confidence interval (95% CI) 0.71, 1.42]), and a 1.85-fold (95% CI 1.20, 2.84) increased preterm birth risk in MotherToBaby. When restricting each sample to women with a high-school diploma or less, preterm birth risk following no OGC exposure was 15.9% in Medi-Cal and 16.7% in MotherToBaby; adjusted RRs were 1.16 (95% CI 0.74, 1.80) in Medi-Cal and 0.81 (95% CI 0.25, 2.64) in MotherToBaby. Cumulative OGC dose was higher in MotherToBaby (median 684 mg) than in Medi-Cal (median 300 mg). An OGC dose of ≤300 mg was not associated with increased preterm birth risk. Exposure misclassification and confounding by RA severity were unlikely explanations of differences. CONCLUSION: Higher baseline preterm birth risk and lower OGC dose distribution in Medi-Cal may explain the discrepancies. Studies are needed to understand the effects of autoimmune disease severity and undertreatment on preterm birth risk in low-income populations.

Longitudinal Methods for Modeling Exposures in Pharmacoepidemiologic Studies in Pregnancy.

In many perinatal pharmacoepidemiologic studies, exposure to a medication is classified as "ever exposed" versus "never exposed" within each trimester or even over the entire pregnancy. This approach is often far from real-world exposure patterns, may lead to exposure misclassification, and does not to incorporate important aspects such as dosage, timing of exposure, and treatment duration. Alternative exposure modeling methods can better summarize complex, individual-level medication use trajectories or time-varying exposures from information on medication dosage, gestational timing of use, and frequency of use. We provide an overview of commonly used methods for more refined definitions of real-world exposure to medication use during pregnancy, focusing on the major strengths and limitations of the techniques, including the potential for method-specific biases. Unsupervised clustering methods, including k-means clustering, group-based trajectory models, and hierarchical cluster analysis, are of interest because they enable visual examination of medication use trajectories over time in pregnancy and complex individual-level exposures, as well as providing insight into comedication and drug-switching patterns. Analytical techniques for time-varying exposure methods, such as extended Cox models and Robins' generalized methods, are useful tools when medication exposure is not static during pregnancy. We propose that where appropriate, combining unsupervised clustering techniques with causal modeling approaches may be a powerful approach to understanding medication safety in pregnancy, and this framework can also be applied in other areas of epidemiology.

Evidence of under-reporting of early-onset preeclampsia using register data.

BACKGROUND: Early-onset preeclampsia, traditionally defined as presenting before 34 gestational weeks, is associated with even higher risks of perinatal death, placental abruption, and stroke, than late-onset preeclampsia. OBJECTIVE: We estimated the degree of misclassification in a high-risk population of lupus pregnancies and a general population comparator when gestational age at delivery defined preeclampsia phenotype compared to first preeclampsia diagnosis. METHODS: Patients with lupus and general population comparators from Sweden with ≥1 singleton pregnancy in the Medical Birth Register with a documented ICD code for preeclampsia were included (2002-2016). We used gestational age at delivery (<34 versus ≥34 weeks) to phenotype preeclampsia early- versus late-onset and then reclassified based on first preeclampsia diagnosis date in the Patient Register. We cross-tabulated the two definitions and calculated sensitivity using the visit-based definition as the reference standard for general population and lupus pregnancies, overall and among nulliparous women. RESULTS: 331 pregnancies were diagnosed with preeclampsia, of which 322 were in both registers. Of those, 58 were early-onset based on gestational age at delivery (n = 29 in lupus pregnancies). Overall, 9% of early-onset preeclampsia in lupus (sensitivity 91%, 95% confidence interval [CI] 75, 98) was misclassified as late-onset compared to 19% in the general population (sensitivity 81%, 95% CI 64, 92). We noted similar misclassification (4% vs 22%) among nulliparous women. CONCLUSIONS: In the general population, early-onset preeclampsia was more likely misclassified as late-onset than in the high-risk lupus population. Relying on gestational age at delivery to phenotype preeclampsia, this way underestimates the occurrence of early-onset preeclampsia. This also suggests that the burden of early-onset preeclampsia as a public health concern may be under-reported, although this may be more applicable to milder preeclampsia where expectant management is employed. Research of biological and maternal predictors of early-onset preeclampsia may be dealing with differentially misclassified outcomes or samples.