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.

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.

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.

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.

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.

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.

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.

"I know my body better than you:" patient focus groups to inform a decision aid on oral corticosteroid use during pregnancy.

PURPOSE: There is unmet need for decision support regarding medication use during pregnancy. We aimed to inform the development of a decision aid on oral corticosteroid (OCS) use during pregnancy through focus groups. METHODS: We invited patients from one health system who had a recent live birth and a condition for which OCSs may be prescribed (ie, asthma or other autoimmune disease) to participate in focus groups. We conducted conventional qualitative content analysis of verbatim transcripts of the focus groups using inductive coding. RESULTS: There were 30 participants across five focus groups from May to June 2019. Women endorsed the need for patient-provider discussions about OCS use during pregnancy in which the provider shares risks and benefits and the patient makes her decision. Furthermore, women generally expressed support for patient-centered handouts about OCS use during pregnancy that the provider discusses with the patient. When considering whether to take OCSs in pregnancy, women had concerns about: the medication's impact on their baby (eg, miscarriage, birth defects, long-term effects), themselves (eg, effects on mood, sleep, weight gain), pregnancy complications (eg, preterm birth, increased blood pressure), and lactation. Women wanted information on OCSs (eg, indications, length of treatment, and cost), alternative treatments, and risks of not taking OCSs. CONCLUSIONS: We established patient need for a decision aid on OCS use during pregnancy that providers can discuss with patients. To address patient concerns, the aid should at a minimum describe the medication's impact on baby, including long-term effects, maternal health, pregnancy complications, and lactation.

Oral corticosteroid use during pregnancy and risk of preterm birth.

OBJECTIVE: To evaluate the associations between oral corticosteroid (OCS) dose early and late in pregnancy and preterm birth (PTB) among women with RA. METHODS: Pregnant women in the MotherToBaby Pregnancy Studies (2003-2014) with RA (n = 528) were included in the primary analysis. Information was collected by phone interview and from medical records. We estimated risk ratios (RR) for OCS dose trajectories and other disease-related medications before gestational day 140 and hazard ratios (HR) for time-varying exposures after gestational day 139. RESULTS: PTB risk was 15.5% overall. Compared with no OCS, PTB risk was increased in high (adjusted (a)RR: 4.77 (95% CI: 2.76, 8.26)) and medium (aRR: 1.81 (95% CI: 1.10, 2.97)) cumulative OCS dose trajectories during the first 139 gestational days. The low cumulative trajectory group was associated with an increased risk of PTB that was not statistically significant (aRR: 1.38 (95% CI: 0.79, 2.38)), and DMARDs were not associated with PTB (biologic DMARDs aHR: 1.08 (95% CI: 0.70, 1.66); non-biologic DMARDs aHR: 0.87 (95% CI: 0.55, 1.38)). OCS exposure to ⩾10 mg of prednisone equivalent daily dose after gestational day 139 vs none was associated with increased PTB rate (aHR: 2.45 (95% CI: 1.32, 4.56)), whereas <10 mg was associated with a modestly increased rate of PTB that was not statistically significant (aHR: 1.18 (95% CI: 0.60, 2.30)). CONCLUSION: Higher OCS doses vs no OCS use, both earlier and later in pregnancy, were associated with an increase in PTB among women with RA.

Acetaminophen use in pregnancy: Examining prevalence, timing, and indication of use in a prospective birth cohort.

BACKGROUND: Previous studies of prenatal acetaminophen use have not addressed what indications and maternal co-factors describe acetaminophen use. OBJECTIVE: The objective of this study was to describe these parameters in a well-characterised, prospective birth cohort. METHODS: Data were drawn from the MotherToBaby study of pregnant women enrolled from 2004 to 2018. Daily acetaminophen diaries were calculated for all exposed women with complete dose and duration information. Descriptive statistics were used to assess maternal characteristics associated with acetaminophen use. Prevalence by 2-year interval was described, and linear regression was used to test for trend. Indication of use and dose per indication were summarised. RESULTS: Of 2441 subjects, 1515 (62%) reported use of acetaminophen. Over the 15-year period, there was a decline in use of 2.5% for each 2-year period (test for trend = 0.001) with 58% reporting acetaminophen use in 2017-2018. Among women with acetaminophen use in pregnancy (n = 1515), 58% reported <10 days of use, 13% reported 10-19 days of use, 9% reported 20-44 days of use, and 9% reported 45 or more days of use. Twelve per cent had undefined duration of use. Increasing duration of exposure was associated with tobacco use, obesity, self-reported depression or anxiety, and antidepressant use. The most frequently reported indication was headache, however, indication varied by duration of use, with more women reporting use for sleep or pain/injury in the categories with the longest duration of use. Median dose per exposed day was highest among those reporting use for sleep, and higher doses were more frequently reported for arthritis, injury, and pain. CONCLUSION: Acetaminophen is used by the majority of pregnant women, and some continue to use for many weeks in pregnancy. Given the heterogeneity in duration of use, indication, and dose, studies that estimate the risk of adverse outcomes associated with acetaminophen must carefully consider these factors.

Patterns of prenatal antidepressant exposure and risk of preeclampsia and postpartum haemorrhage.

BACKGROUND: Antidepressant use later in pregnancy has been associated with preeclampsia and postpartum haemorrhage (PPH) in some studies. OBJECTIVES: To evaluate the association between patterns of prenatal antidepressant dose across gestationand risk of precclampsia and PPH. METHODS: We utilised OptumLabs® Data Warehouse (2012-2016) administrative health care claims, identifying 226 932 singleton liveborn deliveries for this retrospective cohort study. Antidepressant dispensing doses were converted to fluoxetine equivalents. Using k-means longitudinal, we identified women with similar patterns of antidepressant exposure, that is, trajectory groups, during the first 20 and 35 gestational weeks. We estimated risk ratios (RR) and 95% confidence intervals (CI) for the association between trajectory groups and preeclampisa (20-week groups) and PPH (35-week groups), adjusting for demographics, co-morbidities, and other psychotropic medications. Linear trend tests assessing increasing risk of the outcomes across groups were performed. RESULTS: Among 15 041 (6.6%) pregnancies exposed to an antidepressant, the following trajectory groups were identified: A-low exposure, starting pregnancy at ~10 mg/d, with 1st trimester reduction/discontinuation, B-low sustained exposure of ~20 mg/d, C-moderate exposure (~40 mg/d) with 1st trimester reduction/discontinuation, D-moderate sustained exposure of ~40 mg/d, and E-high sustained exposure of ~75 mg/d. In the low exposure with reduction/discontinuation trajectory, risks were 8.2% for preeclampsia and 2.7% for PPH. Compared with this group, low, moderate, and high sustained trajectories were associated with preeclampsia (adjusted RR 1.17, 95% CI 1.01, 1.34; RR 1.31, 95% CI 1.12, 1.54; and RR 1.41, 95% CI 1.05, 1.90, respectively) and PPH (RR 1.32, 95% CI 1.05, 1.66; RR 1.35, 95% CI 1.03, 1.78; RR 2.51, 95% CI 1.69, 3.71, respectively); P < .01 for linear trend tests for both outcomes. There was no increased risk for either outcome for moderate exposure with reduction/discontinuation (trajectory C). CONCLUSIONS: Women with sustained antidepressant exposure, especially at higher doses, were at increased risk for preeclampsia and PPH, but underlying depression and anxiety may contribute to the increased risk.

Asthma prevalence among women aged 18 to 44 in the United States: National health and nutrition examination survey 2001-2016.

Objective: To provide updated prevalence estimates of asthma and asthma medication use for women of childbearing age in the United States.Methods: Using data from 11,383 women aged 18-44, including a subset of 1,245 pregnant women, enrolled in the National Health and Nutrition Examination Survey (2001-2016), we assessed the age-adjusted prevalence of self-reported diagnosed asthma. For women aged 18-44, we stratified by year, demographics, and other characteristics. Furthermore, we assessed asthma medication use among women aged 18-44 with asthma.Results: After age-adjustment, 9.9% (95% confidence interval (CI) 9.2%, 10.7%) of women aged 18-44 and 10.9% (95% CI 7.2%, 14.6%) of pregnant women reported having asthma. Asthma prevalence was highest in 2015-2016 (12.0% 95% CI 9.8%, 14.3%) and lowest in 2003-2004 (8.6% 95% CI 6.4%, 10.8%). Women aged 18-44 with Medicaid or State Children's Health Insurance Program insurance coverage (16.8% 95% CI 14.5%, 19.2%), obesity (14.4% 95% CI 12.9%, 15.8%), diabetes (18.7% 95% CI 12.1%, 25.2%), hypertension (16.6% 95% CI 14.2%, 19.0%), and current smokers (12.8% 95% CI 11.4%, 14.2%) had the highest asthma prevalence. Of women with asthma, 38.3% (95% CI 34.5%, 42.1%) reported using asthma medications in the past 30 days.Conclusions: Among women of childbearing ages, asthma burden varies across demographic and clinical characteristics and has increased in recent years.

Using nationally representative survey data for external adjustment of unmeasured confounders: An example using the NHANES data.

PURPOSE: To evaluate the use of data from population-based surveys such as the National Health and Nutrition Examination Survey (NHANES) for external adjustment for confounders imperfectly measured in health care databases in the United States. METHODS: Our example study used Medicaid Analytic eXtract (MAX) data to estimate the relative risk (RR) for prenatal serotonin-norepinephrine reuptake inhibitors (SNRIs) exposure and cardiac defects. Smoking and obesity are known confounders poorly captured in databases. NHANES collects information on lifestyle factors, depression, and prescription medications. External adjustment requires information on the prevalence of confounders and their association with SNRI use; which was obtained from the NHANES. It also requires estimates of their association with the outcome, which were based on the literature and allowed us to correct the RR using sensitivity analyses. RESULTS: In MAX, the RR for the association between prenatal SNRI exposure and cardiac defects was 1.51 unadjusted and 1.20 adjusted for measured confounders and restricted to women with depression. In NHANES, among women of childbearing age with depression, the prevalence of smoking was 60.2% (95% Confidence Interval 43.2, 74.3) for SNRI users and 44.1% (39.6, 48.8) for nonusers of antidepressants. The corresponding estimates for obesity were 59.2% (43.2, 74.3) and 40.5% (35.9, 45.0), respectively. If the associations between smoking and obesity with cardiac defects are independent from each other and from other measured confounders, additional adjustment for smoking and obesity would move the RR from 1.20 to around 1.10. CONCLUSION: National surveys like NHANES are readily available sources of information on potential confounders and they can be used to assess and improve the validity of RR estimates from observational studies missing data on known risk factors.

Validation of mother-infant linkage using Medicaid Case ID variable within the Medicaid Analytic eXtract (MAX) database.

PURPOSE: The state-assigned Case ID number in the Medicaid Analytic eXtract (MAX) allows for potential linkage of mothers to infants. No validation of respective linkage algorithms is available. We established and validated an algorithm within MAX that links mothers to infants and to identify factors influencing successful mother-infant linkage. METHODS: We identified all mother-infant pairs in FL and TX birth certificates records (BCR) that could be linked individually to MAX records (1999-2005 for FL and 1999-2010 for TX) based on Social Security Number (gold standard pairs). Case ID linkage performance was evaluated as the proportion of gold standard mother-infant pairs that were identified by the algorithm (sensitivity) and the proportion of algorithm defined mother-infant pairs that were correctly linked. Generalized estimating equations were used to calculate the probability for successful Case ID algorithm linkage versus non-linkage using maternal and infant characteristics. RESULTS: We identified 323,160 gold standard pairs in FL BCR and MAX and 1,025,350 in TX BCR and MAX. Depending on Medicaid enrollment the algorithm sensitivity ranged from 85.51% to 87.96% in FL and 19.60% to 35.75% in TX. In both states, positive predictive value exceeded 99%, regardless of enrollment periods. Determinants for successful linkage varied across states, but suggested better results for younger mothers, minority women, and those with lower educational achievement. CONCLUSIONS: Our algorithm can correctly link liveborn infants to their mothers. The algorithm's sensitivity in identifying pairs varied across states, but PPV was consistently high. Linkage performance was associated with certain characteristics that may affect representativeness of successfully linked pairs.

Agreement Between Maternal Report and Medical Records During Pregnancy: Medications for Rheumatoid Arthritis and Asthma.

BACKGROUND: There are limited data regarding the comparability of medication exposure information during pregnancy from maternal report and medical records, including for rheumatoid arthritis and asthma-related medications. METHODS: This study included pregnant women with rheumatoid arthritis (n = 216) and asthma (n = 172) enrolled in the MothertoBaby Pregnancy Studies (2009-2014). Women reported types and dates of medications used through semi-structured telephone interviews up to three times during pregnancy and once after delivery, and medical records were obtained. We calculated Cohen's kappa coefficients and 95% confidence intervals (CIs) and per cent agreement for agreement between report and records. RESULTS: For rheumatoid arthritis, prednisone was reported most frequently (53%). During pregnancy, kappa coefficients for rheumatoid arthritis medications ranged from 0.32 (95% CI 0.15, 0.50) for ibuprofen, with 84.3% agreement, to 0.90 (95% CI 0.84, 0.96) for etanercept with 95.4% agreement, and was 0.44 (95% CI 0.33, 0.55) for prednisone, with 71.3% agreement. For asthma, albuterol was reported most frequently (77.9%). During pregnancy, kappa coefficients for asthma medications ranged from 0.21 (95% CI 0.08, 0.35), with 64.5% agreement for albuterol to 0.84 (95% CI 0.71, 0.96) for budesonide/formoterol, with 96.5% agreement. Where kappas for any use during pregnancy were less than excellent (i.e. ≤0.80), medication use was more frequently captured by report than record. CONCLUSIONS: Agreement was higher for medications typically used continuously than sporadically. Information on medication use from medical records alone may not be adequate when studying the impact of intermittently used medications during pregnancy on perinatal outcomes.

Revisiting the Table 2 fallacy: A motivating example examining preeclampsia and preterm birth.

BACKGROUND: A "Table Fallacy," as coined by Westreich and Greenland, reports multiple adjusted effect estimates from a single model. This practice, which remains common in published literature, can be problematic when different types of effect estimates are presented together in a single table. The purpose of this paper is to quantitatively illustrate this potential for misinterpretation with an example estimating the effects of preeclampsia on preterm birth. METHODS: We analysed a retrospective population-based cohort of 2 963 888 singleton births in California between 2007 and 2012. We performed a modified Poisson regression to calculate the total effect of preeclampsia on the risk of PTB, adjusting for previous preterm birth. pregnancy alcohol abuse, maternal education, and maternal socio-demographic factors (Model 1). In subsequent models, we report the total effects of previous preterm birth, alcohol abuse, and education on the risk of PTB, comparing and contrasting the controlled direct effects, total effects, and confounded effect estimates, resulting from Model 1. RESULTS: The effect estimate for previous preterm birth (a controlled direct effect in Model 1) increased 10% when estimated as a total effect. The risk ratio for alcohol abuse, biased due to an uncontrolled confounder in Model 1, was reduced by 23% when adjusted for drug abuse. The risk ratio for maternal education, solely a predictor of the outcome, was essentially unchanged. CONCLUSIONS: Reporting multiple effect estimates from a single model may lead to misinterpretation and lack of reproducibility. This example highlights the need for careful consideration of the types of effects estimated in statistical models.

Patterns of prednisone use during pregnancy in women with rheumatoid arthritis: Daily and cumulative dose.

PURPOSE: To characterize prednisone use in pregnant women with rheumatoid arthritis using individual-level heat-maps and clustering individual trajectories of prednisone dose, and to evaluate the association between prednisone dose trajectory groups and gestational length. METHODS: This study included pregnant women with rheumatoid arthritis who enrolled in the MotherToBaby Autoimmune Diseases in Pregnancy Study (2003-2014) before gestational week 20 and reported prednisone use without another oral glucocorticoid during pregnancy (n = 254). Information on medication use and pregnancy outcomes was collected by telephone interview plus by medical record review. Prednisone daily dose and cumulative dose were plotted by gestational day using a heat map for each individual. K-means clustering was used to cluster individual trajectories of prednisone dose into groups. The associations between trajectory group and demographics, disease severity measured by the Health Assessment Questionnaire at enrollment, and gestational length were evaluated. RESULTS: Women used prednisone 3 to 292 days during pregnancy, with daily doses ranging from <1 to 60 mg. Total cumulative dose ranged from 8 to 6225 mg. Disease severity, non-biologic disease modifying anti-rheumatic drug use, and gestational length varied significantly by trajectory group. After adjusting for disease severity, non-biologic disease modifying anti-rheumatic drug use, and other covariates, the highest vs lowest daily dose trajectory group was associated with reduced gestational age at delivery (ß: -2.3 weeks (95%: -3.4, -1.3)), as was the highest vs lowest cumulative dose trajectory group (ß: -2.6 weeks (95%: -3.6, -1.5)). CONCLUSIONS: In pregnant women with rheumatoid arthritis, patterns of higher prednisone dose were associated with shorter gestational length compared with lower dose.

Longitudinal trajectories of antidepressant use in pregnancy and the postnatal period.

Studies of antidepressant safety in pregnancy typically do not address complex patterns of use throughout pregnancy. We performed longitudinal trajectory modeling to describe patterns of antidepressant use in the first 32 weeks of pregnancy, and test whether these trajectories are associated with a reduction in birth weight or gestational age at delivery. Our study included 166 pregnant women with deliveries between 2011 and 2015 who were prescribed an antidepressant between 91 days prior to last menstrual period and 32 weeks of gestation. From electronic medical records, we estimated average daily dose and cumulative dose per week for the first 32 weeks of gestation and for the first 13 weeks postnatal. We clustered women with similar utilization patterns using k-means longitudinal modeling and assessed the associations between trajectory group and birth weight and gestational age at delivery. We identified four cumulative dose trajectory groups and three average daily dose trajectory groups in each period. Relative to the lowest trajectory group, the highest trajectory group during pregnancy was associated with reduced birth weight in multivariable analysis (average daily highest trajectory vs. lowest trajectory ß - 314.1 g, 95% CI - 613.7, - 15.5) adjusted for depression severity score, maternal age, race, and pregnancy smoking. Trajectory groups were not associated with gestational age at delivery. The highest trajectory group of antidepressant use in pregnancy was associated with a modest reduction in birth weight but not with gestational age at delivery. Longitudinal trajectories allow for a dynamic visualization and quantification of medication use among pregnant women.

Antidepressant use in pregnancy and the risk of cardiac defects.

BACKGROUND: Whether the use of selective serotonin-reuptake inhibitors (SSRIs) and other antidepressants during pregnancy is associated with an increased risk of congenital cardiac defects is uncertain. In particular, there are concerns about a possible association between paroxetine use and right ventricular outflow tract obstruction and between sertraline use and ventricular septal defects. METHODS: We performed a cohort study nested in the nationwide Medicaid Analytic eXtract for the period 2000 through 2007. The study included 949,504 pregnant women who were enrolled in Medicaid during the period from 3 months before the last menstrual period through 1 month after delivery and their liveborn infants. We compared the risk of major cardiac defects among infants born to women who took antidepressants during the first trimester with the risk among infants born to women who did not use antidepressants, with an unadjusted analysis and analyses that restricted the cohort to women with depression and that used propensity-score adjustment to control for depression severity and other potential confounders. RESULTS: A total of 64,389 women (6.8%) used antidepressants during the first trimester. Overall, 6403 infants who were not exposed to antidepressants were born with a cardiac defect (72.3 infants with a cardiac defect per 10,000 infants), as compared with 580 infants with exposure (90.1 per 10,000 infants). Associations between antidepressant use and cardiac defects were attenuated with increasing levels of adjustment for confounding. The relative risks of any cardiac defect with the use of SSRIs were 1.25 (95% confidence interval [CI], 1.13 to 1.38) in the unadjusted analysis, 1.12 (95% CI, 1.00 to 1.26) in the analysis restricted to women with depression, and 1.06 (95% CI, 0.93 to 1.22) in the fully adjusted analysis restricted to women with depression. We found no significant association between the use of paroxetine and right ventricular outflow tract obstruction (relative risk, 1.07; 95% CI, 0.59 to 1.93) or between the use of sertraline and ventricular septal defects (relative risk, 1.04; 95% CI, 0.76 to 1.41). CONCLUSIONS: The results of this large, population-based cohort study suggested no substantial increase in the risk of cardiac malformations attributable to antidepressant use during the first trimester. (Funded by the Agency for Healthcare Research and Quality and the National Institutes of Health.).