Low and High Ambient Temperatures during Pregnancy and Birth Weight among 624,940 Singleton Term Births in Israel (2010–2014): An Investigation of Potential Windows of Susceptibility

BACKGROUND: Exposure to heat during pregnancy has been associated with reduced fetal growth. Less is known about associations with cold and the potential for critical time windows of exposure. OBJECTIVES: We aimed to evaluate, in a national retrospective cohort, critical windows of susceptibility during pregnancy to extreme temperatures (low and high) and fetal growth, among 624,940 singleton term births in Israel during the period 2010–2014. METHODS: Temperature exposures were estimated using a spatially refined gridded climate data set with a 1-h and [Formula: see text] resolution. Percentiles of temperature were categorized by climatic zone for the entire pregnancy and by trimesters and weeks. Generalized additive models with the distributed lag nonlinear model framework were used to estimate unadjusted and adjusted associations between percentiles and categories of temperature and fetal growth markers: term [births after 36 weeks of gestational age (GA)] mean birth weight and term low birth weight (tLBW, term infants with birth weight below [Formula: see text]). RESULTS: After adjustment, extreme temperatures (percentiles) during the entire pregnancy were associated with a lower mean birth weight {[Formula: see text] vs. 41st–50th percentile: [Formula: see text] [95% confidence interval (CI): [Formula: see text] , [Formula: see text])]; [Formula: see text] vs. 41st–50th percentile: [Formula: see text]; 95% CI: [Formula: see text] , [Formula: see text]}. Similar inverse U-shaped patterns were observed for all trimesters, with stronger associations for heat than for cold and for exposures during the third trimester. For heat, results suggest critical windows between 3–9 and 19–34 GA-weeks, with the strongest association estimated at 3 GA-weeks (temperature [Formula: see text] vs. 41st–50th percentiles: [Formula: see text]; 95% CI: [Formula: see text] , [Formula: see text]). For cold, there was a consistent trend of null associations early in pregnancy and stronger inverse associations over time, with the strongest association at 36 GA-week ([Formula: see text] vs. 41st–50th percentiles: [Formula: see text]; 95% CI: [Formula: see text] , [Formula: see text]). For tLBW, U-shape patterns were estimated for the entire pregnancy and third trimester exposures, as well as nonsignificant associations with heat for 29–36 GA-weeks. Generally, the patterns of associations with temperatures during the entire pregnancy were consistent when stratified by urbanicity and geocoding hierarchy, when estimated for daily minimum and maximum temperatures, when exposures were classified based on temperature distributions in 49 natural regions, and when estimated for all live births. DISCUSSION: Findings from our study of term live births in Israel (2010–2014) suggest that exposure to extreme temperatures, especially heat, during specific time windows may result in reduced fetal growth. https://doi.org/10.1289/EHP8117