Population-based case-control study of the association between weather-related extreme heat events and neural tube defects.

Background: Elevated body core temperature has been shown to have teratogenic effects in animal studies. Our study evaluated the association between weather-related extreme heat events (EHEs) in the summer season and neural tube defects (NTDs), and further investigated whether pregnant women with a high pregestational body mass index (BMI) have a greater risk of having a child with NTDs associated with exposure to EHE than women with a normal BMI.

Methods: We conducted a population-based case-control study among mothers of infants with NTDs and mothers of infants without major birth defects, who participated in the National Birth Defects Prevention Study and had at least 1 day of the third or fourth week postconception during summer months. EHEs were defined using the 95 and the 90 percentiles of the daily maximum universal apparent temperature. Adjusted odds ratios and 95% confidence intervals were calculated using unconditional logistic regression models with Firth's penalized likelihood method while controlling for other known risk factors.

Results: Overall, we did not observe a significant association between EHEs and NTDs. At the climate region level, consistently elevated but not statistically significant estimates were observed for at least 2 consecutive days with daily universal apparent maximum temperature above the 95 percentile of the UATmax distribution for the season, year, and weather monitoring station in New York (Northeast), North Carolina and Georgia (Southeast), and Iowa (Upper Midwest). No effect modification by BMI was observed.

Conclusion: EHEs occurring during the relevant developmental window of embryogenesis do not appear to appreciably affect the risk of NTDs. Future studies should refine exposure assessment, and more completely account for maternal activities that may modify the effects of weather exposure. Birth Defects Research 109:1482-1493, 2017.© 2017 Wiley Periodicals, Inc.