[Association between periconception maternal cold and heat exposure and the risk of congenital heart disease in offspring in China].

Abstract

Objective: To investigate the associations between maternal exposure to cold and heat exposure during the three months before pregnancy and early pregnancy and the risk of congenital heart disease (CHD) in offspring, and to identify critical exposure windows and modifying factors.

Methods: This nationwide cohort study included women aged 20-49 years with complete pregnancy outcome follow-up from the National Free Pre-pregnancy Check-ups Project (NFPCP) database between January 1, 2014 and April 21, 2020. Meteorological data from the European Centre for Medium-Range Weather Forecasts Reanalysis v5 (ERA5) dataset were linked to residential addresses. Cold and heat exposure were defined based on relative thresholds stratified by climate zone: heat and cold were defined as temperatures above the 90th percentile or below the 10th percentile, respectively, of the location-specific temperature distribution during each exposure window. Cox proportional hazards models were used to analyze the associations between cold and heat exposure during the three months before pregnancy and early pregnancy and the risk of CHD, and to calculate hazard ratios (HR) and 95% confidence intervals (CI) after adjusting for maternal age, body mass index (BMI), education level, geographical region, conception season, and relative humidity. Stratified analyses were performed to examine the effects of age, BMI, and fetal sex on the associations between cold and heat exposure and the risk of CHD.

Results: A total of 6 322 635 women aged 20-49 years with complete pregnancy outcome follow-up were included, and 1 478 cases of CHD were diagnosed among their offspring. The analysis showed that heat exposure during the three months before pregnancy was significantly associated with an increased risk of CHD in offspring (HR=1.49, 95%CI: 1.23-1.80); while no significant association was found for heat exposure during early pregnancy. No significant association was observed for cold exposure during the three months before pregnancy and early pregnancy (three months before pregnancy: HR=0.93, 95%CI: 0.77-1.14; early pregnancy: HR=0.95, 95%CI: 0.79-1.16). Stratified analyses showed that the risk of CHD associated with heat exposure during the three months before pregnancy was increased in women aged ≥30 years (HR=2.18, 95%CI: 1.54-3.10) and in male fetuses (HR=1.73, 95%CI: 1.31-2.29); the risk of CHD associated with heat exposure during early pregnancy was significantly increased in women with BMI ≥24 kg/m² (HR=1.86, 95%CI: 1.21-2.87).

Conclusion: Heat exposure during the three months before pregnancy might increase the risk of congenital heart disease in offspring, and this risk was elevated in both women aged ≥30 years and male fetuses. Furthermore, heat exposure during early pregnancy significantly increased the risk of congenital heart disease in offspring among women with BMI ≥24 kg/m². No significant association was observed between cold exposure and the risk of congenital heart disease.