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Background: The use of chlorine to treat drinking water produces disinfection by‐products (DBPs), which have been associated with congenital heart defects (CHDs) in some studies. Methods: Using National Birth Defects Prevention Study data, we linked geocoded residential addresses to public water supply measurement data for DBPs. Self‐reported water consumption and filtration methods were used to estimate maternal ingestion of DBPs. We estimated adjusted odds ratios and 95% confidence intervals using logistic regression controlling for maternal age, education, body mass index (BMI), race/ethnicity, and study site to examine associations between CHDs and both household DBP level and estimated ingestion of DBPs. Results: Household DBP exposure was assessed for 2717 participants (1495 cases and 1222 controls). We observed a broad range of positive, null, and negative estimates across eight specific CHDs and two summary exposures (trihalomethanes and haloacetic acids) plus nine individual DBP species. Examining ingestion exposure among 2488 participants (1347 cases, 1141 controls) produced similarly inconsistent results. Conclusions: Assessing both household DBP level and estimated ingestion of DBPs, we did not find strong evidence of an association between CHDs and DBPs. Despite a large study population, DBP measurements were available for less than half of participant addresses, limiting study power. [ABSTRACT FROM AUTHOR]

BackgroundGastroschisis is a birth defect where loops of bowel are protruding from the abdominal wall at birth. Previous research has suggested that gastroschisis cases can occur in clusters. The objective of this study was to identify if there were areas of elevated gastroschisis risk using data from the National Birth Defects Prevention Study (NBDPS), 1997 through 2007.MethodsWe obtained data on cases (n = 371) through population-based birth defects surveillance systems in Arkansas, California, and Utah; controls (n = 2359) were selected from the same geographic areas as cases. Mothers were interviewed on demographic information and exposures during pregnancy, including residential history. We used first trimester maternal addresses and generalized additive models to create a continuous map surface of odds ratios (OR) by smoothing over latitude and longitude. Permutation tests were used to assess whether location of maternal residence was important and identify locations with statistically significant ORs.ResultsIn Arkansas, adjusted ORs in the southwest corner were 2.0 and the global deviance was not statistically significant (p-value: 0.57). Adjusted ORs for California indicated areas of increased risk with ORs 1.3 (p-value: 0.34). In Utah, the adjusted ORs were elevated (OR: 2.4) in the south-eastern corner of the study area (p-value: 0.34).ConclusionThe results of this study, while not statistically significant, suggest there were spatial variations in gastroschisis births. We cannot rule out that these variations were due to edge effects or residual confounding.

PurposePrevious research has suggested gastroschisis, a congenital malformation, may be linked to environmental or infectious factors and cases can occur in clusters. The objective of this study was to identify geographic areas of elevated gastroschisis risk.MethodsCases of gastroschisis were identified from birth defect registries in Massachusetts and Texas. Random samples of live births were selected as controls. Generalized additive models were used to create a continuous map surface of odds ratios (ORs) by smoothing over latitude and longitude. Maternal age, race/ethnicity, education, cigarette smoking, and insurance status (MA only) were assessed for confounding. We used permutation tests to identify statistically significant areas of increased risk.ResultsAn area of increased risk was identified in North Central Massachusetts but was not significant after adjustment (P value = .07; OR = 2.0). In Texas, two statistically significant areas of increased risk were identified after adjustment (P value = .02; OR = 1.3 and 1.2). Texas had sufficient data to assess the combination of space and time, which identified an increased risk in 2003 and 2004.ConclusionsThis study suggests there were areas of elevated gastroschisis risk in Massachusetts and Texas, which cannot be explained by the risk factors we assessed. Additional exploration of underlying artifactual, environmental, infectious, or behavioral factors may further our understanding of gastroschisis.

Background: There are few assessments evaluating associations between birth defects with neural crest cell developmental origins (BDNCOs) and embryonal tumors, which are characterized by undifferentiated cells having a molecular profile similar to neural crest cells. The effect of BDNCOs on embryonal tumors was estimated to explore potential shared etiologic pathways and genetic origins. Methods: With the use of a multistate, registry‐linkage cohort study, BDNCO–embryonal tumor associations were evaluated by generating hazard ratios (HRs) and 95% confidence intervals (CIs) with Cox regression models. BDNCOs consisted of ear, face, and neck defects, Hirschsprung disease, and a selection of congenital heart defects. Embryonal tumors included neuroblastoma, nephroblastoma, and hepatoblastoma. Potential HR modification (HRM) was investigated by infant sex, maternal race/ethnicity, maternal age, and maternal education. Results: The risk of embryonal tumors among those with BDNCOs was 0.09% (co‐occurring n = 105) compared to 0.03% (95% CI, 0.03%–0.04%) among those without a birth defect. Children with BDNCOs were 4.2 times (95% CI, 3.5–5.1 times) as likely to be diagnosed with an embryonal tumor compared to children born without a birth defect. BDNCOs were strongly associated with hepatoblastoma (HR, 16.1; 95% CI, 11.3–22.9), and the HRs for neuroblastoma (3.1; 95% CI, 2.3–4.2) and nephroblastoma (2.9; 95% CI, 1.9–4.4) were elevated. There was no notable HRM by the aforementioned factors. Conclusions: Children with BDNCOs are more likely to develop embryonal tumors compared to children without a birth defect. Disruptions of shared developmental pathways may contribute to both phenotypes, which could inform future genomic assessments and cancer surveillance strategies of these conditions. Associations between nonchromosomal birth defects of neural crest cell developmental origins and pediatric embryonal tumors were investigated based on potential shared developmental pathways. With the use of data from a multistate, registry‐linkage cohort study, children born with these birth defects were found to be more likely (hazard ratio, 4.2; 95% CI, 3.5–5.1) to be diagnosed with the selected embryonal tumors than children without a birth defect, especially hepatoblastoma (hazard ratio, 16.1; 95% CI, 11.3–22.9). [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: Vitamin D deficiency is associated with adverse pregnancy events. However, its role in the etiology of congenital anomalies remains unclear. We examined the association between vitamin D status, measured through prepregnancy diet, UV exposure, season of conception, and congenital anomalies. Methods: We used data from the National Birth Defects Prevention Study, a U.S. population‐based case–control study (1997–2011). Prepregnancy dietary vitamin D was calculated from food frequency questionnaires and evaluated using tertiles, based on the distribution in controls. We used the National Oceanic and Atmospheric Administration Weather Service to assign UV indices based on location and estimated date of conception, then dichotomized UV exposure (low vs. high). Seasons of conception was categorized as fall/winter spring/summer. We used logistic regression to estimate adjusted odds ratios (aOR) and 95% confidence intervals (CI). Results: Lower prepregnancy dietary vitamin D intake (<65.21 IU/d vs. >107.55 IU/d) was associated with increased odds of anencephaly (aOR = 1.28, 95% CI 1.01, 1.63), hypospadias (aOR = 1.21, 95% CI 1.04, 1.40), septal defects (aOR = 1.16, 95% CI 1.05, 1.30), diaphragmatic hernia (aOR = 1.42, 95% CI 1.13, 1.79), and gastroschisis (aOR = 1.27, 95% CI 1.07, 1.52). Findings were consistent when we stratified by UV exposure and season of conception. Conclusions: Our findings suggest lower dietary intake of vitamin D may be associated with increased risk of select congenital anomalies. Further investigations are warranted to evaluate the effects of other nutrients and appropriate thresholds and sources of vitamin D using serum. [ABSTRACT FROM AUTHOR]

Background: SARS‐CoV‐2 infection during pregnancy has been linked to preterm birth, but this association is not well understood. Objectives: To examine the association between SARS‐CoV‐2 infection and spontaneous and provider‐initiated preterm birth (PTB), and how timing of infection, and race/ethnicity as a marker of structural inequality, may modify this association. Methods: We conducted a retrospective cohort study among pregnant people who delivered singleton, liveborn infants (22–44 weeks gestation) from 1 March 2020 to 31 March 2021 (n = 68,288). We used Cox proportional hazards models to compare the hazard of PTB between pregnant people with and without laboratory‐confirmed SARS‐CoV‐2 infection during pregnancy. We evaluated this association according to the trimester of infection, timing from infection to birth, and timing of PTB. We also examined the joint associations of SARS‐CoV‐2 infection and race/ethnicity with PTB using the relative excess risk due to interaction (RERI). Results: Positive SARS‐CoV‐2 tests were identified for 2195 pregnant people (3.2%). The prevalence of PTB was 7.2% (3.8% spontaneous, 3.6% provider‐initiated). SARS‐CoV‐2 infection during pregnancy was associated with an increased risk of PTB overall (adjusted hazard ratio [HR] 1.53, 95% confidence interval [CI] 1.34, 1.74), and provider‐initiated PTB (HR 1.79, 95% CI 1.50, 2.12) but not spontaneous PTB (HR 1.09, 95% CI 0.89, 1.36). Second trimester infections were associated with an increased risk of provider‐initiated PTB, and third trimester infections were associated with an increased risk of both PTB subtypes. A joint inverse association between White non‐Hispanic race/ethnicity and SARS‐CoV‐2 infection and spontaneous PTB (HR 0.56, 95% CI 0.34, 0.94; RERI −0.6, 95% CI −1.0, −0.2) was also observed. Conclusions: SARS‐CoV‐2 infections were primarily associated with an increased risk for provider‐initiated PTB in this study. These findings highlight the importance of promoting infection‐prevention strategies among pregnant people. [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: Both short and long interpregnancy intervals (IPIs) have been associated with adverse birth outcomes. We undertook a multistate study to describe the prevalence of selected birth defects by IPI. Methods: We obtained data from nine population‐based state birth defects registries for singleton live births in 2000–2009 among mothers with a previous live birth identified through birth certificates. IPI was calculated as the difference between prior birthdate and start of the current pregnancy (conception date). We estimated prevalence of selected defects per 10,000 live births and prevalence ratios (PRs) with 95% confidence intervals (CIs) overall and stratified by maternal age at previous birth and race/ethnicity. Primary analyses focused on short IPI < 6 months and long IPI ≥ 60 months compared to 18–23 months (referent). Sensitivity analyses limited to active‐surveillance states and those with<10% missing IPI. Results: Among 5,147,962 eligible births, 6.3% had short IPI while 19.8% had long IPI. Compared to referent, prevalence with short IPI was elevated for gastroschisis (3.7, CI: 3.0–4.5 vs. 2.0, CI: 1.6–2.4) and with both short and long IPI for tetralogy of Fallot (short: 3.4, 2.8–4.2 long: 3.8, 3.4–4.3 vs. 2.7, 2.3–3.2) and cleft lip ± palate (short: 9.9, 8.8–11.2 long: 9.2, 8.5–9.8 vs. 8.4, 7.6–9.2). Stratified analyses identified additional associations, including elevated prevalence of anencephaly with short IPI in younger mothers and limb defects with long IPI in those ages 25–34 at prior birth. Sensitivity analyses showed similar results. Conclusion: In this population‐based study, we observed increased prevalence of several birth defects with short and long IPI. [ABSTRACT FROM AUTHOR]