Search

Background: Nausea and vomiting of pregnancy (NVP) occurs in approximately 70% of pregnant people, with varying severity and duration. Treatments include pharmacologic and herbal/natural medications. The associations between NVP and birth outcomes, including preterm birth, small for gestational age (SGA), and low birth weight are inconclusive. Objective: To determine whether NVP and reported medications are associated with adverse birth outcomes. Methods: We used data from the population‐based, multisite National Birth Defects Prevention Study (1997–2011) to evaluate whether self‐reported NVP according to timing, duration, and severity or its specific treatments were associated with preterm birth, SGA, and low birth weight among controls without birth defects. Odds ratios (aOR) and 95% confidence intervals (CI) were adjusted for sociodemographic, reproductive, and medical factors. For any NVP, duration, treatment use, and severity score analyses, the comparison group was participants with no reported NVP. For timing analyses, the comparison group was women with no reported NVP in the same trimester of pregnancy. Results: Among 6018 participants, 4339 (72.1%) reported any NVP. Among those with NVP, moderate or severe symptoms were more common than mild symptoms. Any versus no NVP was not associated with any of the outcomes of interest. NVP in months 4–6 (aOR 1.21, 95% CI: 1.00, 1.47) and 7–9 (aOR 1.57, 95% CI: 1.22, 2.01) of pregnancy were associated with an increase in the risk of preterm birth. NVP lasting one trimester in duration was associated with decrease in risk of SGA (aOR: 0.74, 95% CI: 0.58, 0.95), and NVP present in every trimester of pregnancy had a 50% increase in risk of preterm birth (aOR: 1.50, 95% CI: 1.11, 2.05). For NVP in months 7–9 and preterm birth, ORs were elevated for moderate (aOR: 1.82, 95% CI: 1.26, 2.63), and severe (aOR: 1.53, 95% CI: 1.06, 2.19) symptoms. NVP was not significantly associated with low birth weight. Our analyses of medications were limited by small numbers, but none suggested increased risk of adverse outcomes associated with use of the medication. Conclusion: Mild NVP and NVP limited to early pregnancy appear to have no effect or a small protective effect on birth outcomes. Long‐lasting NVP, severe NVP, and NVP later in pregnancy may increase risk of preterm birth and SGA. [ABSTRACT FROM AUTHOR]

Background: Fungal infections are common among pregnant people. Recent studies suggest positive associations between oral antifungals used to treat fungal infections and congenital heart defects (CHDs). Methods: We estimated associations between first trimester antifungal use and 20 major, specific CHDs using data from the National Birth Defects Prevention Study (NBDPS), a multi‐site, case–control study that included pregnancies with estimated delivery dates from October 1997 through December 2011. Infants with CHDs ("cases") were ascertained from 10 birth defect surveillance programs. Live born infants without major birth defects ("controls") were randomly selected from birth records or hospital discharge lists. First trimester antifungal use was self‐reported via maternal interview. We estimated adjusted odds ratios (AORs) and 95% confidence intervals (CIs) using logistic regression with Firth's penalized likelihood. Results: First trimester antifungal use was reported by 148/11,653 (1.3%) case and 123/11,427 (1.1%) control participants. We estimated AORs for 12 CHDs; six had AORs >1.5 (tetralogy of Fallot, double outlet right ventricle with transposition of the great arteries [DORV‐TGA], atrioventricular septal defect, hypoplastic left heart syndrome, pulmonary atresia, muscular ventricular septal defect), and one (pulmonary valve stenosis) had an AOR <0.7. All CIs included the null, except for DORV‐TGA. Conclusions: First trimester antifungal use was rare. We observed some positive associations for several specific CHDs in our analysis, although the CIs largely included the null. Results do not support a large increase in risk, but smaller increases in risk for certain CHD cannot be ruled out. [ABSTRACT FROM AUTHOR]

Aims: Talipes equinovarus (clubfoot) is a congenital lower foot deformity that results from a neuromuscular deficiency, but the precise etiology remains elusive. Vitamin D is important for fetal neuromuscular development. In this study, we investigated the association between dietary vitamin D intake during pregnancy and incidence of clubfoot in neonates, since such a question has thus far been overlooked. Methods: We conducted a secondary analysis of data collected in the United States, between 2007 and 2011 for a case–control study of children born with clubfoot. Participating mothers were interviewed by telephone about dietary and other health and life‐style indicators. Exposure to vitamin D was recorded as the average daily intake of dietary vitamin D over a period of 6 months before pregnancy began. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression. Results: The dataset included 2667 study participants, of which 663 were cases. Logistic regression showed no significant association between dietary vitamin D or log10(Vitamin D) intake during pregnancy and incidence of clubfoot in neonates (OR = 1.00, CI = 1.00–1.00, OR = 1.51, CI = 0.83–2.82, respectively). No interaction in the regression model was found between vitamin D and other predictor variables. Results were not confounded by supplement intake of vitamin D during pregnancy. Conclusions: Results show no evidence of an association between dietary vitamin D intake and incidence of clubfoot in neonates. The lack of association is not confounded by consumption of vitamin D supplements during pregnancy. [ABSTRACT FROM AUTHOR]

Background: Gastroschisis prevalence more than doubled between 1995 and 2012. While there are individual‐level risk factors (e.g., young maternal age, low body mass index), the impact of environmental exposures is not well understood. Methods: We used the U.S. Environmental Protection Agency's Environmental Quality Index (EQI) as a county‐level estimate of cumulative environmental exposures for five domains (air, water, land, sociodemographic, and built) and overall from 2006 to 2010. Adjusted odds ratios (aOR) and 95% confidence interval (CI) were estimated from logistic regression models between EQI tertiles (better environmental quality (reference); mid; poorer) and gastroschisis in the National Birth Defects Prevention Study from births delivered between 2006 and 2011. Our analysis included 594 cases with gastroschisis and 4105 infants without a birth defect (controls). Results: Overall EQI was modestly associated with gastroschisis (aOR [95% CI]: 1.29 [0.98, 1.71]) for maternal residence in counties with poorer environmental quality, compared to the reference (better environmental quality). Within domain‐specific indices, only the sociodemographic domain (aOR: 1.51 [0.99, 2.29]) was modestly associated with gastroschisis, when comparing poorer to better environmental quality. Conclusions: Future work could elucidate pathway(s) by which components of the sociodemographic domain or possibly related psychosocial factors like chronic stress potentially contribute to risk of gastroschisis. [ABSTRACT FROM AUTHOR]

Background: Two strong risk factors for gastroschisis are young maternal age (<20 years) and low/normal pre‐pregnancy body mass index (BMI), yet the reasons remain unknown. We explored whether neighborhood‐level socioeconomic position (nSEP) during pregnancy modified these associations. Methods: We analyzed data from 1269 gastroschisis cases and 10,217 controls in the National Birth Defects Prevention Study (1997–2011). To characterize nSEP, we applied the neighborhood deprivation index and used generalized estimating equations to calculate odds ratios and relative excess risk due to interaction. Results: Elevated odds of gastroschisis were consistently associated with young maternal age and low/normal BMI, regardless of nSEP. High‐deprivation neighborhoods modified the association with young maternal age. Infants of young mothers in high‐deprivation areas had lower odds of gastroschisis (adjusted odds ratio [aOR]: 3.1, 95% confidence interval [CI]: 2.6, 3.8) than young mothers in low‐deprivation areas (aOR: 6.6; 95% CI: 4.6, 9.4). Mothers of low/normal BMI had approximately twice the odds of having an infant with gastroschisis compared to mothers with overweight/obese BMI, regardless of nSEP (aOR range: 1.5–2.3). Conclusion: Our findings suggest nSEP modified the association between gastroschisis and maternal age, but not BMI. Further research could clarify whether the modification is due to unidentified biologic and/or non‐biologic factors. [ABSTRACT FROM AUTHOR]

Background: Studies evaluating associations between medication use in pregnancy and birth outcomes rely on various sources of exposure information. We sought to assess agreement between self‐reported use of medications during early pregnancy and medication information in prenatal medical records to understand the reliability of each of these information sources. Methods: We compared self‐reported prescription medication use in early pregnancy to medical records from 184 New York women with deliveries in 2018 who participated in the Birth Defects Study To Evaluate Pregnancy exposureS. We assessed medications used chronically and episodically, and medications within 12 therapeutic groups. We calculated agreement using kappa (κ) coefficients, sensitivity, and specificity. We assessed differences by case/control status, maternal age, education, time to interview, and interview language. Results: Medications used chronically showed substantial agreement between self‐report and medical records (κ = 0.75, 0.61–0.88), with agreement for therapeutic groups used chronically ranging from κ = 0.61 for antidiabetics to κ = 1.00 for antihypertensives. Prescription medications used episodically showed worse agreement (κ = 0.40, 0.25–0.54), with the lowest agreement for opioid analgesics (κ = 0.20) and anti‐infectives (κ = 0.33). Agreement did not differ by the characteristics examined, although we observed potential differences by interview language. Conclusions: Among our sample, we observed good agreement between self‐report and medical records for medications used chronically and substantially less agreement for medications used episodically. Differences by source may be due to poor recall in self‐reports, non‐adherence with prescribed medications and lack of complete prescription information within medical records. Limitations should be considered when assessing prescription medication exposures during early pregnancy in epidemiologic studies. [ABSTRACT FROM AUTHOR]

Background: Nausea and vomiting of pregnancy (NVP) occurs in approximately 70% of pregnant people. Treatments include pharmacologic and herbal/natural products. Research on the associations between NVP and its treatments and birth defects is limited. Methods: We used data from the case–control National Birth Defects Prevention Study (1997–2011) to examine whether first‐trimester NVP or its specific treatments were associated with 37 major birth defects. Odds ratios (aOR) and 95% confidence intervals (CIs) were adjusted for sociodemographic and reproductive factors. Results: Mothers of 66.6% of 28,628 cases and 69.9% of 11,083 controls reported first‐trimester NVP. Compared to no NVP, mothers with NVP had ≥10% reduction in risk of cardiac and noncardiac defects overall, and of 18 specific defects. Over‐the‐counter antiemetic use, compared to untreated NVP, was associated with ≥10% increase in risk for nine defect groups (heterotaxy, hypoplastic left heart syndrome [HLHS], aortic stenosis, cataracts, anophthalmos/microphthalmos, biliary atresia, transverse limb deficiency, omphalocele, and gastroschisis), whereas use of prescription antiemetics increased risk ≥10% for seven defect groups (tetralogy of Fallot, HLHS, spina bifida, anopthlamos/microphthalmos, cleft palate, craniosynostosis, and diaphragmatic hernia). We observed increased risks for promethazine and tetralogy of Fallot (aOR: 1.49, 95% CI: 1.05–2.10), promethazine and craniosynostosis (1.44, 1.08–1.92), ondansetron and cleft palate (1.66, 1.18–2.31), pyridoxine and heterotaxy (3.91, 1.49–10.27), and pyridoxine and cataracts (2.57, 1.12–5.88). Conclusions: NVP does not increase risks of birth defects. Our findings that some treatments for NVP increase risk of specific birth defects should be investigated further before clinical recommendations are made. [ABSTRACT FROM AUTHOR]

Background: Many previous studies have identified risk factors for stillbirth, but few examine stillbirth among pregnancies affected with birth defects. Because many hypothesized etiologies of stillbirth work through vascular pathologies of the placenta, we examined maternal use of vasoactive medications in relation to stillbirth among pregnancies affected with birth defects. Methods: Data were analyzed from the National Birth Defects Prevention Study (1997–2011). We examined use of nonsteroidal anti‐inflammatory drugs (NSAIDs), decongestants, short‐ or long‐acting beta‐agonists (SABA/LABA), and antihypertensive medications in relation to pregnancies affected by birth defects ending in stillbirth compared to live birth. Associations were measured with odds ratios (ORs) for early pregnancy use and hazard ratios (HRs) for time‐varying late pregnancy use. Results: Among all birth defects (n = 12,394), the risk of stillbirth was associated with use of antihypertensive medications in early (odds ratio [OR]: 1.8; 95% confidence interval [CI]: 1.0, 3.1) and late pregnancy (HR: 2.0; 95% CI: 1.1, 3.6). Other vasoactive medications were not associated with increased risk of stillbirth. Of 27 specific defect groups, increased risks were observed for only one medication/defect pair: early decongestant use was more common among mothers of stillbirth versus live birth cases with spina bifida (OR: 2.4; 95% CI: 0.9, 6.5). Conclusion: This exploratory analysis of vasoactive medication use suggests that use of NSAIDs, decongestants, and SABA/LABA is not associated with increased risk of stillbirth among pregnancies affected with birth defects. Our finding of increased risks associated with antihypertensive medication use raises questions of confounding by indication, which we were not able to fully address. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Benzodiazepine medications can be used to treat anxiety, a condition affecting 15% of women of childbearing age in the United States. Studies have shown conflicting results for the association between benzodiazepine use during pregnancy and birth defects. Methods: We analyzed 1997–2011 data from the National Birth Defects Prevention Study, a multisite, population‐based case–control study. We assessed the prevalence of and factors associated with benzodiazepine use in pregnancy among mothers of live‐born infants without a birth defect (control mothers). We used logistic regression to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for the association between specific birth defects and benzodiazepine use; we estimated crude odds ratios (cORs) for defect categories with 3–4 exposed cases. Results: Exposure to benzodiazepines during pregnancy was rare (N = 93/11,614; 0.8%). Benzodiazepine use was more common among control mothers who were ≥30 years, non‐Hispanic white, had more education, smoked, and took antidepressant medication. We observed significantly elevated ORs for any benzodiazepine and Dandy–Walker malformation (cOR: 3.1; 95% CI: 1.1, 8.6); for alprazolam and anophthalmia or microphthalmia (cOR: 4.0; 95% CI: 1.2, 13.1) and esophageal atresia or stenosis (aOR: 2.7; 95% CI: 1.2, 5.9); and lorazepam and pulmonary valve stenosis (cOR: 4.1; 95% CI: 1.2, 14.2), but sample sizes were limited and therefore CIs were wide. Conclusions: Our findings suggest that benzodiazepines use is rare and may be associated with risk for certain birth defects. However, these results need replication and should be interpreted with caution. [ABSTRACT FROM AUTHOR]

Background: There are limited data on the relationship between antihypertensive medication use in early pregnancy and risk of birth defects. Methods: Using data from the National Birth Defects Prevention Study, we examined associations between specific antihypertensive medication classes and 28 noncardiac birth defects. We analyzed self‐reported data on 17,038 case and 11,477 control pregnancies with estimated delivery dates during 1997–2011. We used multivariable logistic regression to estimate odds ratios (ORs) and 95% confidence intervals, adjusted for maternal age, race/ethnicity, body mass index, parity, pregestational diabetes, and study site, for associations between individual birth defects and antihypertensive medication use during the first trimester of pregnancy. We compared risk among women reporting early pregnancy antihypertensive medication use to normotensive women. Results: Hypertensive women who reported early pregnancy antihypertensive medication use were more likely to be at least 35 years old, non‐Hispanic Black, obese, multiparous, and to report pregestational diabetes than normotensive women. Compared to normotensive women, early pregnancy antihypertensive medication use was associated with increased risk of small intestinal atresia (adjusted OR 2.4, 95% CI 1.2–4.7) and anencephaly (adjusted OR 1.9, 95% CI 1.0–3.5). Risk of these defects was not specific to any particular medication class. Conclusions: Maternal antihypertensive medication use was not associated with the majority of birth defects we analyzed, but was associated with an increased risk for some birth defects. Because we cannot entirely rule out confounding by the underlying hypertension and most ORs were based on small numbers, the increased risks observed should be interpreted with caution. [ABSTRACT FROM AUTHOR]

Background: Gastroschisis, a birth defect of the abdominal wall, is increasing in prevalence. The largest increase in prevalence has been observed among young mothers (<20 years). The prevalence of Chlamydia trachomatis (CT) infection is highest among young women and has also been increasing over time. The objective was to investigate the association between immunoglobulin G antibodies to Chlamydia trachomatis (CT) (anti-CT) and Chlamydial heat shock protein 60 (anti-CHP60) during pregnancy, and risk of gastroschisis among offspring. Methods: We conducted a nested case-control study of 292 gastroschisis cases identified from the Congenital Malformations Register and 826 live born controls matched on age and birth year within the Finnish Maternity Cohort. Early pregnancy serum samples were used to categorize women by seropositivity to anti-CT and anti-CHP60. Women seronegative for anti-CT and anti-CHP60 served as the reference. We used conditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Effect measure modification by maternal age (<25 years, -25 years) was also assessed. Results: Seropositivity to anti-CT (17.8% of cases vs. 16.0% of controls) or anti-CHP60 (23.6% of cases vs. 22.0% of controls) was not associated with gastroschisis. Although, the OR for seropositivity to anti-CT alone was slightly elevated (OR, 1.19; 95% CI, 0.73- 1.94), specifically among young mothers (<25 years) (OR, 1.65; 95% CI, 0.81-3.37), the results were imprecise. Conclusion: Chlamydia infection, as measured by immunoglobulin G antibodies to CT and CHP60, is not associated with gastroschisis, however, our assays were not able to distinguish recent infection. [ABSTRACT FROM AUTHOR]

Background: Although many factors are associated with gastroschisis risk, studies have not systematically explored whether they account for its increasing frequency over the past decades or its inverse association with maternal age. We examined whether previously reported risk factors for gastroschisis from the National Birth Defects Prevention Study (NBDPS) explain the association with increasing temporal prevalence or young maternal age., Methods: Using data from the NBDPS (1997-2011), crude odds ratios (ORs) were calculated for birth years 2005-2011 versus 1997-2004 and maternal age < 25 versus 25+ years. We then adjusted for 16 factors separately with logistic regression (paternal age, interpregnancy interval, parity, alcohol, cigarettes, illicit drugs, oral contraceptives, cold/flu with fever, genitourinary infection, polycyclic aromatic hydrocarbons, diet quality, prepregnancy body mass index, parental race and ethnicity, language spoken at home, years lived in the United States, and household income)., Results: The birth year OR (1.28; 95% CI: 1.14, 1.44) was attenuated by 16% after adjustment for polycyclic aromatic hydrocarbon exposure (OR 1.08; 95 CI: 0.92, 1.26). The young maternal age OR (7.76; 95% CI: 6.71, 8.97) was attenuated by 30% after adjustment for paternal age (OR 5.43; 95% CI: 4.55, 6.48) and separately for interpregnancy interval (OR 5.45; 95% CI: 4.43, 6.69)., Conclusion: Some evidence suggests that risk factors for gastroschisis account for small amounts of the time trend and maternal age associations. However, it remains unclear what factors underlie the complete calendar time or maternal age associations., (© 2025 Wiley Periodicals LLC.)