Paternal occupational exposure to chemicals and secondary sex ratio: results from the Japan Environment and Children's Study

Summary Background Declining proportions of male births have been reported in several industrialised countries. Previous reports have shown that exposure to certain chemical substances might influence the secondary sex ratio (SSR). We assessed the associations between paternal occupational exposure to chemicals and the SSR of their children using the Japan Environment and Children's Study (JECS), a large-scale birth cohort study. Methods Data on paternal occupational exposure to various agents and other covariates were collected using a self-administered questionnaire to partners of pregnant female participants enrolled in the JECS. After adjusting for potential confounders, multivariable modified Poisson regression models were used to evaluate associations between paternal occupational exposures and the SSR of their children. This study was registered in the UMIN Clinical Trials Registry, number UMIN000030786. Findings The JECS study gathered data on 103 062 pregnancies, 104 065 fetuses, and 51 898 partners of pregnant women. Among 50 283 children with data on paternal occupational exposures, 25 657 were male and 24 626 were female. The proportion of boys whose fathers were regularly occupationally exposed to insecticides was 0·445 (males, n=293; females, n=366; 95% CI 0·406–0·483), which was lower than the proportion of boys whose fathers were not exposed to insecticides. After adjusting for confounding factors, regular paternal occupational exposure to insecticides (adjusted relative risk 0·86, 95% CI 0·78–0·96) and medical disinfectants (0·95, 0·90–1·00) were significantly associated with lower SSRs among their offspring compared with the offspring of fathers not exposed to these substances. Interpretation A declining proportion of boys could potentially be due to fathers working in environments in which they are exposed to chemicals. The associations between poorer semen quality and levels of reproductive and thyroid hormones require investigation. Funding Ministry of the Environment of Japan.