Threshold and sex-specific associations of prenatal low-level lead exposure with neonatal birth outcomes: a Chinese prospective birth cohort study

BACKGROUND: Even low-level prenatal lead exposure may adversely affect fetal development, yet its impact on neonatal birth outcomes and potential sex-specific effects remain unclear in general populations. We aimed to assess the associations between low-level prenatal lead exposure and neonatal anthropometric outcomes, and to investigate sex-specific susceptibility. METHODS: We utilized data from a prospective birth cohort established in Wujiang District, Jiangsu Province, China, including 2020 mother-infant pairs. Cord blood lead levels were measured at delivery by using graphite furnace atomic absorption spectrometry. Neonatal birthweight, length, and head circumference were recorded. Multiple linear regression models were used to assess associations between log-transformed lead concentrations and birth outcomes, with stratification by infant sex. Dose-response relationships were examined by using restricted cubic splines (RCSs) and threshold effects were tested via piecewise linear regression. RESULTS: The median cord blood lead concentration was 32.10 μg/L [95% confidence interval (CI): 31.40, 32.82 μg/L]. Higher cord blood lead concentrations were significantly associated with reduced head circumference (adjusted β = -0.314 cm per 1-unit increase in log10 Pb; 95% CI: -0.502, -0.126; P = .001) but not with birthweight or length. Sex-stratified analysis revealed that this association was significant in males (adjusted β = -0.461 cm per 1-unit increase in log10 Pb; 95% CI: -0.735, -0.188; P = .001) but not in females. RCS models demonstrated a nonlinear relationship, with a threshold at ∼40 μg/L, above which the head circumference declined more steeply. This threshold effect persisted in males. CONCLUSION: Prenatal exposure to lead is associated with reduced neonatal head circumference, with evidence of sex-specific vulnerability and threshold effects. These findings underscore the need for stringent environmental monitoring and suggest that head circumference may serve as a sensitive biomarker of early lead toxicity, even at low exposure levels.