Maternal PM2.5 exposure and hypospadias risk in Chinese offspring: Insights from a nationwide surveillance-based study.

Research on the association between maternal PM2.5 exposure and hypospadias risk in male offspring, particularly in highly polluted areas, has been limited and inconsistent. This study leveraged data from China's National Population-based Birth Defects Surveillance System spanning the years 2013 to 2019, and employed sophisticated machine learning models to estimate daily PM2.5 levels and other pollutants for mothers at a 1-km resolution and a 6-km buffer surrounding maternal residences. Multivariate logistic regression analyses were performed to evaluate the relationship between PM2.5 exposure and hypospadias risk. For sensitivity analyses, stratification analysis was conducted, and models for one-pollutant and two-pollutants, as well as distributed lag nonlinear models, were constructed. Of the 1194,431 boys studied, 1153 cases of hypospadias were identified. A 10 μg/m3 increase in maternal PM2.5 exposure during preconception and the first trimester was associated with an elevated risk of isolated hypospadias, with Odds Ratios (ORs) of 1.102 (95% CI: 1.023-1.188) and 1.089 (95% CI: 1.007-1.177) at the 1-km grid, and 1.122 (95% CI: 1.034-1.218) and 1.143 (95% CI: 1.048-1.246) within the 6-km buffer. Higher quartiles of PM2.5 exposure were associated with increased odds ratios compared to the lowest quartile. These findings highlight a significant association between PM2.5 exposure during the critical conception period and an elevated risk of isolated hypospadias in children, emphasizing the need for targeted interventions to reduce PM2.5 exposure among expectant mothers.