Birth Outcomes Related to Prenatal Zika, Dengue, and Other Flavivirus Infections in the Zika en Embarazadas y Niños Prospective Cohort Study in Colombia.

Zika virus (ZIKV) infection in pregnancy is associated with severe abnormalities of the brain and eye and other adverse outcomes. Zika en Embarazadas y Niños was a prospective cohort study conducted in multiple Colombian cities that enrolled pregnant women in their first trimester. Specimens collected from pregnant women (n = 1,519) during February 2017-September 2018 and their infants (n = 1,080) during June 2017-March 2019 were tested for prenatal ZIKV infection by nucleic acid amplification tests or IgM antibody testing. Zika virus infection in pregnancy was present in 3.2% of pregnant women (incidence rate [IR] per 1,000 person-months = 5.9, 95% CI: 4.3-7.8). Presumptive ZIKV infection was present in 0.8% of infants (IR = 1.6, 95% CI: 0.7-2.9). Five percent of infants with prenatal ZIKV exposure or infection presented with Zika-associated abnormalities; 4.7% were small for gestational age. Understanding the risk of ZIKV infection during pregnancy and associated adverse outcomes can help inform counseling efforts.

Real World Data are Not Always Big Data: The Case for Primary Data Collection on Medication Use in Pregnancy in the Context of Birth Defects Research.

Many examples of the use of real-world data in the area of pharmacoepidemiology include "big data" such as insurance claims, medical records, or hospital discharge databases. However, "big" is not always better, particularly when studying outcomes with narrow windows of etiologic relevance. Birth defects are one such outcome, where specificity of exposure timing is critical. Studies with primary data collection can be designed to query details on the timing of medication use, as well as type, dose, frequency, duration, and indication, that can better characterize the "real world". Because birth defects are rare, etiologic studies are typically case-control in design, like the National Birth Defects Prevention Study, Birth Defects Study to Evaluate Pregnancy exposureS, and Slone Birth Defects Study. Recall bias can be a concern, but the ability to collect detailed information on both prescription and over-the-counter medication use and on other exposures such as diet, family history, and sociodemographic factors is a distinct advantage over claims and medical record data sources. Case-control studies with primary data collection are essential to advancing the pharmacoepidemiology of birth defects.

Maternal physical activity, sitting, and risk of non-cardiac birth defects.

BACKGROUND: The relationship between maternal physical activity (PA)/sitting and birth defects is largely unexplored. We examined whether pre-pregnancy PA/sitting were associated with having a pregnancy affected by a birth defect. METHODS: We used data from two United States population-based case-control studies: 2008-2011 deliveries from the National Birth Defects Prevention Study (NBDPS; 9 states) and 2014-2018 deliveries from the Birth Defects Study To Evaluate Pregnancy exposureS (BD-STEPS; 7 states). Cases with one of 12 non-cardiac birth defects (n = 3798) were identified through population-based registries. Controls (n = 2682) were live-born infants without major birth defects randomly sampled using vital/hospital records. Mothers self-reported pre-pregnancy PA/sitting. Unconditional logistic regression models estimated associations between PA/sitting categories and the 12 birth defects. RESULTS: Mothers engaging in pre-pregnancy PA was associated with a reduced odds of five (spina bifida, cleft palate, anorectal atresia, hypospadias, transverse limb deficiency) and a higher odds of two (anencephaly, gastroschisis) birth defects. Mothers spending less time sitting in pre-pregnancy was associated with a reduced odds of two (anorectal atresia, hypospadias) and a higher odds of one (cleft lip with or without cleft palate) birth defect. CONCLUSIONS: Reasonable next steps include replication of these findings, improved exposure assessment, and elucidation of biologic mechanisms. IMPACT: Using data from two population-based case-control studies, we found that mothers engaging in different types of physical activity in the 3 months before pregnancy had an infant with a reduced odds of five and a higher odds of two birth defects. Mothers spending less time sitting in the 3 months before pregnancy had an infant with a reduced odds of two and a higher odds of one birth defect. Clarification and confirmation from additional studies are needed using more precise exposure measures, distinguishing occupational from leisure-time physical activity, and elucidation of mechanisms supporting these associations.

Maternal exposure to zolpidem and risk of specific birth defects.

Zolpidem is a non-benzodiazepine agent indicated for treatment of insomnia. While zolpidem crosses the placenta, little is known about its safety in pregnancy. We assessed associations between self-reported zolpidem use 1 month before pregnancy through to the end of the third month ("early pregnancy") and specific birth defects using data from two multi-site case-control studies: National Birth Defects Prevention Study and Slone Epidemiology Center Birth Defects Study. Analysis included 39,711 birth defect cases and 23,035 controls without a birth defect. For defects with ≥ 5 exposed cases, we used logistic regression with Firth's penalised likelihood to estimate adjusted odds ratios and 95% confidence intervals, considering age at delivery, race/ethnicity, education, body mass index, parity, early-pregnancy antipsychotic, anxiolytic, antidepressant use, early-pregnancy opioid use, early-pregnancy smoking, and study as potential covariates. For defects with three-four exposed cases, we estimated crude odds ratios and 95% confidence intervals. Additionally, we explored differences in odds ratios using propensity score-adjustment and conducted a probabilistic bias analysis of exposure misclassification. Overall, 84 (0.2%) cases and 46 (0.2%) controls reported early-pregnancy zolpidem use. Seven defects had sufficient sample size to calculate adjusted odds ratios, which ranged from 0.76 for cleft lip to 2.18 for gastroschisis. Four defects had odds ratios > 1.8. All confidence intervals included the null. Zolpidem use was rare. We could not calculate adjusted odds ratios for most defects and estimates are imprecise. Results do not support a large increase in risk, but smaller increases in risk for certain defects cannot be ruled out.

Fever and antibiotic use in maternal urinary tract infections during pregnancy and risk of congenital heart defects: Findings from the National Birth Defects Prevention Study.

BACKGROUND: Previous studies report an association between prenatal maternal urinary tract infections (UTI) and specific congenital heart defects (CHDs); however, the role of fever and antibiotic use on this association is poorly understood. Using data from the National Birth Defects Prevention Study, we examined whether the relationship between maternal UTIs during the periconceptional period and occurrence of CHDs is modified by the presence of fever due to UTI and corresponding antibiotic use among 11,704 CHD case infants and 11,636 live-born control infants. METHODS: Information on UTIs, fever associated with UTI and antibiotic use (sulfonamides, nitrofurantoin, cephalosporins, penicillin, macrolides, and quinolones) during pregnancy were obtained using a computer-assisted telephone interview. Using unconditional multivariable logistic regression, we calculated adjusted odds ratios (ORs) to determine the association between maternal UTIs and subtypes of CHDs. Analyses were stratified by the presence of fever and medication use associated with UTI. RESULTS: The prevalence of UTIs during the periconceptional period was 7.6% in control mothers, and 8.7% in case mothers. In the absence of fever, UTI was associated with secundum atrial septal defects (ASD) (OR 1.3; 95% confidence interval [CI] 1.1-1.5) and in the absence of antibiotics, UTI was associated with conotruncal defects as a group and for four specific CHDs. When fever and UTI occurred concomitantly, no significantly elevated odds ratios were noticed for any subtypes of CHD. Among women with UTIs who used antibiotics, an elevated but statistically non-significant estimate was observed for secundum ASD (OR 1.4; 95% CI 1.0-2.0). CONCLUSION: Findings in the present study suggest that fever due to UTI and corresponding maternal antibiotic use do not substantially modify the association between maternal UTIs and specific CHDs in offspring. Further studies with larger sample sizes are warranted to guide clinical management of UTIs during the periconceptional period.

Bias analyses to investigate the impact of differential participation: Application to a birth defects case-control study.

BACKGROUND: Certain associations observed in the National Birth Defects Prevention Study (NBDPS) contrasted with other research or were from areas with mixed findings, including no decrease in odds of spina bifida with periconceptional folic acid supplementation, moderately increased cleft palate odds with ondansetron use and reduced hypospadias odds with maternal smoking. OBJECTIVES: To investigate the plausibility and extent of differential participation to produce effect estimates observed in NBDPS. METHODS: We searched the literature for factors related to these exposures and participation and conducted deterministic quantitative bias analyses. We estimated case-control participation and expected exposure prevalence based on internal and external reports, respectively. For the folic acid-spina bifida and ondansetron-cleft palate analyses, we hypothesized the true odds ratio (OR) based on prior studies and quantified the degree of exposure over- (or under-) representation to produce the crude OR (cOR) in NBDPS. For the smoking-hypospadias analysis, we estimated the extent of selection bias needed to nullify the association as well as the maximum potential harmful OR. RESULTS: Under our assumptions (participation, exposure prevalence, true OR), there was overrepresentation of folic acid use and underrepresentation of ondansetron use and smoking among participants. Folic acid-exposed spina bifida cases would need to have been ≥1.2× more likely to participate than exposed controls to yield the observed null cOR. Ondansetron-exposed cleft palate cases would need to have been 1.6× more likely to participate than exposed controls if the true OR is null. Smoking-exposed hypospadias cases would need to have been ≥1.2 times less likely to participate than exposed controls for the association to falsely appear protective (upper bound of selection bias adjusted smoking-hypospadias OR = 2.02). CONCLUSIONS: Differential participation could partly explain certain associations observed in NBDPS, but questions remain about why. Potential impacts of other systematic errors (e.g. exposure misclassification) could be informed by additional research.

Neighborhood Deprivation and Neural Tube Defects.

BACKGROUND: Individual measures of socioeconomic status (SES) have been associated with an increased risk of neural tube defects (NTDs); however, the association between neighborhood SES and NTD risk is unknown. Using data from the National Birth Defects Prevention Study (NBDPS) from 1997 to 2011, we investigated the association between measures of census tract SES and NTD risk. METHODS: The study population included 10,028 controls and 1829 NTD cases. We linked maternal addresses to census tract SES measures and used these measures to calculate the neighborhood deprivation index. We used generalized estimating equations to calculate adjusted odds ratios (aORs) and 95% confidence intervals (CIs) estimating the impact of quartiles of census tract deprivation on NTDs adjusting for maternal race-ethnicity, maternal education, and maternal age at delivery. RESULTS: Quartiles of higher neighborhood deprivation were associated with NTDs when compared with the least deprived quartile (Q2: aOR = 1.2; 95% CI = 1.0, 1.4; Q3: aOR = 1.3, 95% CI = 1.1, 1.5; Q4 (highest): aOR = 1.2; 95% CI = 1.0, 1.4). Results for spina bifida were similar; however, estimates for anencephaly and encephalocele were attenuated. Associations differed by maternal race-ethnicity. CONCLUSIONS: Our findings suggest that residing in a census tract with more socioeconomic deprivation is associated with an increased risk for NTDs, specifically spina bifida.

Maternal occupational exposure to selected organic and chlorinated solvents and delivery of small-for-gestational age or preterm infants.

BACKGROUND: Potential reproductive effects of organic solvent exposure during pregnancy remain unclear. We investigated the association between maternal occupational exposure during pregnancy to six chlorinated solvents, three aromatic solvents, and Stoddard solvent, and delivery of preterm infants or those born small-for-gestational age (SGA). METHODS: In this case-control study of SGA and preterm birth (PTB) nested within the National Birth Defects Prevention Study (NBDPS) from 1997 to 2011, we analyzed data from 7504 singleton live births without major birth defects and their mothers. Self-reported information on jobs held in the periconceptional period was assessed for solvent exposure. Unconditional logistic regression was used to estimate the association between maternal occupational exposure (any, none) during early pregnancy to organic solvents and PTB and SGA. Linear regression was used to examine changes in mean birthweight potentially associated with maternal occupational solvent exposure. RESULTS: Maternal occupational exposure to any organic solvents overall was not associated with an increased odds of PTB (adjusted odds ratio [aOR] = 0.94; 95% confidence interval [CI] 0.67-1.33) or SGA (aOR = 0.93; 95% CI 0.65-1.34). Point estimates increased modestly for higher estimated exposure versus lower, but confidence intervals were wide and not statistically significant. Maternal exposure to solvents was not associated with a statistically significant change in term birthweight among infants. CONCLUSIONS: Occupational exposure to organic solvents at the frequency and intensity levels found in a population-based sample of pregnant workers was not associated with PTB or SGA; however, we cannot rule out any effects among pregnant workers with uncommonly high exposure to organic solvents.

Inpatient Hospitalization Costs Associated with Birth Defects Among Persons Aged <65 Years - United States, 2019.

Changing treatments and medical costs necessitate updates to hospitalization cost estimates for birth defects. The 2019 National Inpatient Sample was used to estimate the service delivery costs of hospitalizations among patients aged <65 years for whom one or more birth defects were documented as discharge diagnoses. In 2019, the estimated cost of these birth defect-associated hospitalizations in the United States was $22.2 billion. Birth defect-associated hospitalizations bore disproportionately high costs, constituting 4.1% of all hospitalizations among persons aged <65 years and 7.7% of related inpatient medical costs. Updating estimates of hospitalization costs provides information about health care resource use associated with birth defects and the financial impact of birth defects across the life span and illustrates the need to determine the continued health care needs of persons born with birth defects to ensure optimal health for all.

Patterns of Prescription Medication Use during the First Trimester of Pregnancy in the United States, 1997-2018.

The objective of this analysis was to describe patterns of prescription medication use during pregnancy, including secular trends, with consideration of indication, and distributions of use within demographic subgroups. We conducted a descriptive secondary analysis using data from 9,755 women whose infants served as controls in two large United States case-control studies from 1997-2011 and 2014-2018. After excluding vitamin, herbal, mineral, vaccine, i.v. fluid, and topical products and over-the-counter medications, the proportion of women that reported taking at least one prescription medication in the first trimester increased over the study years, from 37% to 50% of women. The corresponding proportions increased with increasing maternal age and years of education, were highest for non-Hispanic White women (47%) and lowest for Hispanic women (24%). The most common indication for first trimester use of a medication was infection (12-15%). Increases were observed across the years for medications used for indications related to nausea/vomiting, depression/anxiety, infertility, thyroid disease, diabetes, and epilepsy. The largest relative increase in use among women was observed for medications to treat nausea/vomiting, which increased from 3.8% in the earliest years of the study (1997-2001) to 14.8% in 2014-2018, driven in large part by ondansetron use. Prescription medication use in the first trimester of pregnancy is common and increasing. Many medical conditions require treatments among pregnant women, often involving pharmacotherapy, which necessitates consideration of the risk and safety profiles for both mother and fetus.

Identification of pregnancies and their outcomes in healthcare claims data, 2008-2019: An algorithm.

Pregnancy is a condition of broad interest across many medical and health services research domains, but one not easily identified in healthcare claims data. Our objective was to establish an algorithm to identify pregnant women and their pregnancies in claims data. We identified pregnancy-related diagnosis, procedure, and diagnosis-related group codes, accounting for the transition to International Statistical Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) diagnosis and procedure codes, in health encounter reporting on 10/1/2015. We selected women in Merative MarketScan commercial databases aged 15-49 years with pregnancy-related claims, and their infants, during 2008-2019. Pregnancies, pregnancy outcomes, and gestational ages were assigned using the constellation of service dates, code types, pregnancy outcomes, and linkage to infant records. We describe pregnancy outcomes and gestational ages, as well as maternal age, census region, and health plan type. In a sensitivity analysis, we compared our algorithm-assigned date of last menstrual period (LMP) to fertility procedure-based LMP (date of procedure + 14 days) among women with embryo transfer or insemination procedures. Among 5,812,699 identified pregnancies, most (77.9%) were livebirths, followed by spontaneous abortions (16.2%); 3,274,353 (72.2%) livebirths could be linked to infants. Most pregnancies were among women 25-34 years (59.1%), living in the South (39.1%) and Midwest (22.4%), with large employer-sponsored insurance (52.0%). Outcome distributions were similar across ICD-9 and ICD-10 eras, with some variation in gestational age distribution observed. Sensitivity analyses supported our algorithm's framework; algorithm- and fertility procedure-derived LMP estimates were within a week of each other (mean difference: -4 days [IQR: -13 to 6 days]; n = 107,870). We have developed an algorithm to identify pregnancies, their gestational age, and outcomes, across ICD-9 and ICD-10 eras using administrative data. This algorithm may be useful to reproductive health researchers investigating a broad range of pregnancy and infant outcomes.

Maternal cyclobenzaprine exposure and risk of birth defects in the National Birth Defects Prevention Study (1997-2011) and Birth Defects Study to Evaluate Pregnancy exposureS (2014-2018).

PURPOSE: Cyclobenzaprine is a muscle relaxant indicated for acute pain. Little is known about cyclobenzaprine's safety during pregnancy. We explored the association between maternal cyclobenzaprine exposure and risk of birth defects among offspring. METHODS: We combined data from two large, multi-site, population-based case-control studies in the United States. Cases were identified from birth defects registries across 10 states; controls were liveborn infants without birth defects randomly selected from the same catchment areas. Participants reported cyclobenzaprine use during the month before conception through the third month of pregnancy ("periconception") via computer-assisted telephone interview. We used logistic regression to assess associations between periconceptional cyclobenzaprine exposure and selected structural birth defects. We calculated crude odds ratios (OR) with corresponding 95% confidence intervals (CI). RESULTS: Our study included 33 615 cases and 13 110 controls. Overall, 51 case (0.15%) and 9 control (0.07%) participants reported periconceptional cyclobenzaprine use. We observed increased risk for all seven defects with ≥3 exposed cases: cleft palate (OR = 4.79, 95% CI 1.71-13.44), cleft lip (OR = 2.50, 95% CI 0.89-7.02), anorectal atresia/stenosis (OR = 6.91, 95% CI 1.67, 28.65), d-transposition of the great arteries (OR = 6.97, 95% CI 2.17-22.36), coarctation of the aorta (OR = 5.58, 95% CI 1.88-16.58), pulmonary valve stenosis (OR = 4.55, 95% CI 1.10-18.87), and secundum atrial septal defect (OR = 3.08, 95% CI 0.83-11.45). CONCLUSIONS: Even in our large sample, cyclobenzaprine use was rare. Our estimates are unadjusted and imprecise so should be interpreted cautiously. These hypothesis-generating results warrant confirmation and further research to explore possible mechanisms.

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.

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.

Using a Birth Defects Surveillance Program to Enhance Existing Surveillance of Stillbirth.

Objective: Fetal death certificates (FDCs) are the main source of stillbirth surveillance data in the United States, yet previous studies suggest FDCs have incomplete ascertainment. The objectives of this analysis were (1) to evaluate whether the use of an existing birth defects surveillance program (the Metropolitan Atlanta Congenital Defects Program [MACDP]) to conduct surveillance on stillbirths enhances case ascertainment, and (2) to compare stillbirth prevalence estimates in metropolitan Atlanta using data from MACDP and FDCs, independently and combined, from 2009-2015. Methods: Stillbirths were ascertained by MACDP and FDCs from 2009-2015. Capture-recapture methods were used to estimate the relative contributions of each data source. Prevalence estimates generated from each data source independently and combined were compared. Results: There were 3,031 stillbirths ascertained by FDCs and MACDP in metropolitan Atlanta from 2009-2015. It was assumed that 35% of FDCs unlinked to MACDP were misclassified as stillbirth. Under this assumption, an estimated 2,610 total stillbirths occurred. Accounting for potential misclassification in the FDC, the prevalence rate for stillbirth was 6.9 per 1,000 live births plus stillbirths for stillbirths captured only in FDC, and 6.2 per 1,000 live births plus stillbirths for stillbirths caught only in MACDP. Using both sources combined for casefinding, the prevalence rate was 10.0 per 1,000 live births plus stillbirths for all years combined. Conclusions: Expanding certain birth defects surveillance programs to conduct surveillance on stillbirths could potentially enhance existing surveillance data on stillbirths when linked to FDCs.

Characteristics of Women with Urinary Tract Infection in Pregnancy.

Background: Urinary tract infection (UTI) is the most common bacterial infection in pregnancy. Known risk factors for UTI in pregnancy include diabetes and certain urologic conditions. Other maternal characteristics might also be associated with risk and could provide clues to the etiology of UTI in pregnancy. Our objective was to identify maternal characteristics associated with UTI in pregnancy. Materials and Methods: We used data from pregnant women participating in the National Birth Defects Prevention Study, a population-based study of risk factors for major structural birth defects in 10 U.S. sites, from 1997 to 2011. In cross-sectional analyses, we used multivariable log-binomial regression to estimate prevalence ratios (PRs) and 95% confidence intervals (CIs) for associations between self-reported maternal characteristics and UTI in pregnancy. Results: In our sample of 41,869 women, the overall prevalence of reported UTI in pregnancy was 18%, but ranged from 11% to 26% between study sites. In adjusted models, diabetes was moderately associated with higher UTI prevalence (PR 1.39, 95% CI: 1.24-1.57). Higher UTI prevalence was associated even more strongly with low educational attainment (PR 2.06, 95% CI: 1.77-2.40 for some high school vs. graduate school), low household income (PR 1.64, 95% CI: 1.46-1.84 for <$10,000 vs. ≥$50,000), and race/ethnicity (PR 1.45, 95% CI: 1.13-1.80 for American Indian or Alaska Native vs. White women). Conclusions: About one in six women reported UTI in pregnancy but the prevalence varied markedly by geography and maternal characteristics. This variability could provide clues to the causes of UTI in pregnancy.

Maternal exposure to hydroxychloroquine and birth defects.

BACKGROUND: Hydroxychloroquine is a treatment for rheumatic disease and considered safe during pregnancy. Interest in hydroxychloroquine has increased as it is being examined as a potential treatment and prophylaxis for coronavirus disease 2019. Data on the risks of specific birth defects associated with hydroxychloroquine use are sparse. METHODS: Using data from two case-control studies (National Birth Defects Prevention Study and Slone Epidemiology Center Birth Defects Study), we described women who reported hydroxychloroquine use in pregnancy and the presence of specific major birth defects in their offspring. Cases had at least one major birth defect and controls were live-born healthy infants. Women self-reported medication use information in the few months before pregnancy through delivery. RESULTS: In total, 0.06% (19/31,468) of case and 0.04% (5/11,614) of control mothers in National Birth Defects Prevention Study, and 0.04% (11/29,838) of case and 0.05% (7/12,868) of control mothers in Birth Defects Study reported hydroxychloroquine use. Hydroxychloroquine users had complicated medical histories and frequent medication use for a variety of conditions. The observed birth defects among women taking hydroxychloroquine were varied and included nine oral cleft cases; the elevated observed:expected ratios for specific oral cleft phenotypes and for oral clefts overall had 95% confidence intervals that included 1.0. CONCLUSION: While teratogens typically produce a specific pattern of birth defects, the observed birth defects among the hydroxychloroquine-exposed women did not present a clear pattern, suggesting no meaningful evidence for the risk of specific birth defects. The number of exposed cases is small; results should be interpreted cautiously.

Venlafaxine prescription claims among insured women of reproductive age and pregnant women, 2011-2016.

BACKGROUND: Some studies have reported associations between prenatal use of venlafaxine, a serotonin-norepinephrine reuptake inhibitor used for depressive and anxiety disorders, and some birth defects. We described the prevalence of venlafaxine prescription claims among privately insured women of reproductive age and pregnant women. METHODS: Venlafaxine prescription claims were examined using the IBM MarketScan Commercial Databases. We included women of reproductive age (15-44 years) who had ≤45 days of lapsed enrollment during the calendar year of interest (2011-2016) in a non-capitated healthcare plan sponsored by a large, self-insured employer with prescription drug coverage and no mental health service carve-out. Annual cohorts of pregnant women were identified among eligible women of reproductive age via pregnancy diagnosis and procedure codes. Venlafaxine prescriptions were identified via National Drug Codes in outpatient pharmacy claims and we estimated the annual proportion of women with venlafaxine claims by pregnancy trimester (pregnant women only), age, and Census division. RESULTS: Each year during 2011-2016, approximately 1.2% of eligible reproductive-aged and 0.3% of eligible pregnant women filled a venlafaxine prescription. Among pregnant women, the proportion with venlafaxine claims was highest during the first trimester and decreased during the second and third trimesters. Small temporal increases in venlafaxine claims were observed for reproductive-aged and pregnant women, with the largest among women aged 15-19 years. CONCLUSIONS: Venlafaxine prescription claims were low among women of reproductive age and pregnant women during 2011-2016, with some increasing use over time among women aged 15-19 years.

Opioid prescription claims among women aged 15-44 years-United States, 2013-2017.

OBJECTIVE: To estimate the annual percentage of women of reproductive age with private insurance or Medicaid who had opioid prescription claims during 2013-2017 and describe trends over time. DESIGN: A secondary analysis of insurance claims data from IBM MarketScan® Commercial and Multi-State Medicaid Databases to assess outpatient pharmacy claims for prescription opioids among women aged 15-44 years during 2013-2017. PARTICIPANTS: Annual cohorts of 3.5-3.8 million women aged 15-44 years with private insurance and 0.9-2.1 million women enrolled in Medicaid. MAIN OUTCOME MEASURE: The percentage of women aged 15-44 years with outpatient pharmacy claims for opioid prescriptions. RESULTS: During 2013-2017, the proportion of women aged 15-44 years with private insurance who had claims for opioid prescriptions decreased by 22.1 percent, and among women enrolled in Medicaid, the proportion decreased by 31.5 -percent. CONCLUSIONS: Opioid prescription claims decreased from 2013 to 2017 among insured women of reproductive age. However, opioid prescription claims remained common and were more common among women enrolled in Medicaid than those with private insurance; additional strategies to improve awareness of the risks associated with opioid prescribing may be needed.

Epidemiology of cytomegalovirus Infection among mothers and infants in Colombia.

We assessed maternal and infant cytomegalovirus (CMV) infection in Colombia. Maternal serum was tested for CMV immunoglobulin G antibodies at a median of 10 (interquartile range: 8-12) weeks gestation (n = 1501). CMV DNA polymerase chain reaction was performed on infant urine to diagnose congenital (≤21 days of life) and postnatal (>21 days) infection. Maternal CMV seroprevalence was 98.1% (95% confidence interval [CI]: 97.5%-98.8%). Congenital CMV prevalence was 8.4 (95% CI: 3.9%-18.3%; 6/711) per 1000 live births. Among 472 infants without confirmed congenital CMV infection subsequently tested at age 6 months, 258 (54.7%, 95% CI: 50.2%-59.1%) had postnatal infection.