Environmental heat and cold stress, thyrotropin abnormalities, and reduced fecundability in 14 million Chinese couples: A nationwide preconception cohort study.

BACKGROUND

Epidemiological studies on ambient thermal stress and fecundability are limited, and previous evidence is based on air temperature rather than a biothermal metric. Additionally, it remains unknown whether thyrotropin abnormalities serve as mediators or modifiers of the effect of thermal stress on fecundability.

METHODS

We performed a nationwide cohort analysis among 14,029,184 couples from the National Free Prepregnancy Checkups Project in 31 provinces in China from 2014 to 2020. Heat and cold stress were estimated by the Universal Thermal Climate Index based on individual residential addresses. Heat (cold) stress was defined as UTCI >90th (<10th) percentiles of the province-specific distribution during the warm (cold) season. Fecundability was measured by time to pregnancy in menstrual cycles. Thyrotropin levels were measured in female participants. Accelerated failure time models were used to examine the association between thermal stress and fecundability. A 4-way decomposition mediation analysis was used to quantify the mediation and modification effects of thyrotropin abnormalities.

RESULTS

We showed that exposure to heat stress and cold stress prior to (heat: time ratio [TR], 1.104; 95% CI, 1.101-1.107; cold: TR, 1.224; 95% CI, 1.221-1.228) and during pregnancy planning (heat: TR, 1.253; 95% CI, 1.248-1.259; cold: TR, 1.259; 95% CI, 1.254-1.264) was associated with reduced fecundability. Positive associations were found between heat stress and subnormal thyrotropin levels (odds ratio [OR], 1.044; 95% CI, 1.031-1.057), as well as between cold stress and supranormal thyrotropin levels (OR, 1.050; 95% CI, 1.040-1.060). Thyrotropin abnormalities could potentially mediate 1.2%-3.9% of the association of heat and cold stress with fecundability. The reference interaction of heat and cold stress with thyrotropin abnormalities accounted for 3.3%-12.1% of the total excess effect, though was not at statistically significant level.

CONCLUSION

This study provides evidence that exposure to both heat and cold stress is associated with reduced fecundability, highlighting the necessity of integrating climate adaptation strategies to mitigate reproductive risks under climate change and accelerated demographic shifts.