Prenatal Exposures to High Ambient Temperatures and Heatwaves Increase the Risk of Necrotizing Enterocolitis: Evidence from Twin Pairs across China.

OBJECTIVE: The association between necrotizing enterocolitis (NEC) and prenatal heat exposure has not been adequately studied. We estimated the association of prenatal high ambient temperature (TM) and heatwave exposure with NEC and to identified susceptible exposure windows. METHODS: Generalized linear models were applied to examine the associations between high TM and heatwaves exposures with NEC. Mediation analysis was used to investigate the role of preterm birth (PTB) in the relationship between high TM and NEC during pregnancy. RESULTS: We included 8,334 twin pairs and their mothers: 227 (2.72%) twin pairs were NEC cases. Compared to the reference temperature (19.8 °C), prenatal exposure to the 90th percentile TM (24.8 °C) was associated with NEC risk [odds ratio ( OR), 2.68; 95% confidence interval ( CI): 1.93-3.72]. Trimester-specific ORs were 2.41 (95% CI: 1.63-3.55), 3.30 (95% CI: 2.18-4.99), and 2.06 (95% CI: 1.43-2.98) for the first, second, and third trimesters, respectively. Exposure to heatwaves during the entire pregnancy, first, and second trimesters showed ORs of 1.98 (95% CI: 1.14-3.43), 1.81 (95% CI: 1.26-2.59), and 1.81 (95% CI: 1.19-2.75), respectively. PTB mediated the association between the 90th and 95th percentile TM exposure during the entire pregnancy and NEC, with the mediation proportions of 30.10% (95% CI: 8.57-45.28) and 36.20% (95% CI: 16.18-50.28), respectively. CONCLUSION: Prenatal exposure to high TM levels and heat waves, especially in the first and second trimesters, was positively associated with the risk of NEC. PTB may partially mediate the relationshipbetween high TM exposure and NEC.