Impact of cord blood cadmium concentration on neonatal secondary sex ratio: The Japan Environment and Children's Study.

The secondary sex ratio (SSR) is the male-to-female birth ratio per 100 female births, typically slightly favoring males. Recent declines in SSR suggest environmental factors, such as cadmium (Cd), may contribute. While cadmium is harmful to human health, its impact on SSR is unclear. This study examined the association between cord blood Cd concentrations and SSR. We used data from the Japan Environment and Children's Study, a nationwide birth cohort. After excluding women with insufficient data, 4296 singleton pregnant women with measured cord blood Cd concentrations were included. Participants were grouped into quintiles based on Cd concentrations. The primary outcome was SSR, and secondary outcomes were histories of ≥1 and ≥2 miscarriages. Multiple logistic regression analyses were used to calculate adjusted odds ratios (aORs) and 95 % confidence intervals (95 % CIs), with the lowest quintile (Q1) as the reference. Maternal medical background, socioeconomic status, preconception nutritional intake, and obstetric complications were considered as confounding factors. The overall SSR was 102.8, with the SSRs in Q1 being 111.9 and in Q5 being 94.4. Multiple logistic regression analysis showed fewer male births in Q5 compared to Q1 (aOR, 0.81; 95 % CI, 0.67-0.99). However, no significant differences in miscarriage history were observed between the quintile groups. Subgroup analyses revealed a stronger negative association between Cd concentrations and male births among women with a history of miscarriage (Q5; aOR, 0.54; 95 % CI, 0.35-0.86), with a statistically significant linear trend (P = 0.047). In conclusion, we observed fewer male infants in the highest compared to the lowest quintiles of cord blood Cd concentrations. This association was more pronounced among women with a history of miscarriage, suggesting a potential vulnerability in this subgroup. Further studies are needed to understand the underlying biological mechanisms involved.