Maternal ambient heat exposure during early pregnancy in summer and spring and congenital heart defects – A large US population-based, case control study
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Background/Objective: Few studies have assessed the effect of ambient heat during the fetal development period on congenital heart defects (CHDs), especially in transitional seasons. We examined and compared the associations between extreme heat and CHD phenotypes in summer and spring, assessed their geographical differences, and compared different heat indicators. Methods: We identified 5,848 CHD cases and 5,742 controls (without major structural defects) from the National Birth Defects Prevention Study, a United States multicenter, population-based case-control study. Extreme heat events (EHEs) were defined by using 95th (EHE95) or 90th (EHE90) percentile of daily maximum temperature and its frequency and duration during postconceptional weeks 3-8. We used a two-stage Bayesian hierarchical model to examine both regional and study-wide associations. Exposure odds ratios (ORs) were calculated using multivariate logistic regression analyses, while controlling for potential confounding factors. Results: Overall, we observed no consistent relationships between maternal EHE exposure and CHDs in most regions. However, we found that 3-15 days of EHE90 in both summer and spring was significantly associated with ventricular septal defects (VSDs) study-wide (ORs ranged: 2.17-3.23). EHE95 in spring were significantly associated with conotruncal defects and VSDs in the South (ORs: 1.23-1.78). Most EHE indicators in spring were significantly associated with increased septal defects (both VSDs and atrial septal defects (ASDs)) in the Northeast. Conclusion: While generally null results were found, long duration of unseasonable heat was associated with the increased risks for VSDs and ASDs, mainly in South and Northeast of US. Further research to confirm our findings is needed.