Association between pre/perinatal exposure to POPs and children's anogenital distance at age 4 years: A study from the INMA-Asturias cohort

Background: Prenatal exposure to endocrine-disrupting chemicals may impair genital development and alter reproductive tract anatomy. Anogenital distance (AGD) is a useful biomarker of exposure to chemicals that act as endocrine disruptors. We evaluated associations between prenatal and perinatal exposure to several persistent organic pollutants (POPs) and AGD in 4-year-old children. Methods: Data were drawn from the INMA-Asturias cohort. Pediatricians measured the anofourchetal distance in female children and anoscrotal distance in male children. The anogenital index (AGI) was defined as the AGD divided by the child's weight at age of examination. We measured the levels of two hexachlorocyclohexane isomers, hexachlorobenzene, dichlorodiphenyltrichloroethane (DDT) and its metabolites, six polychlorinated biphenyl (PCB) congeners, and six polybrominated diphenyl ether (PBDE) congeners in maternal serum at 12 gestational weeks (n = 155) and in cord blood serum (n = 229). Anthropometric and parental sociodemographic variables were collected via face-to-face interviews. Linear regression models were used to evaluate the relationship between exposure to POPs and AGI, adjusted for confounders and stratified by sex. Results: In male children, we found inverse associations between AGI and maternal concentrations of PCB-138 (beta = -0.041, 95% confidence interval [CI]: -0.074, -0.008, second tertile), PCB-153 (beta = -0.052, 95% CI: -0.085, -0.020, second tertile), PCB-180 beta = -0.065, 95% CI: -0.096, -0.035, second tertile; beta = -0.042, 95% CI: -0.073, -0.011, third tertile), PBDE-209 (beta = -0.031, 95% CI: -0.058, -0.006), cord serum concentrations of PCB-153 (beta = -0.029, 95% CI: -0.059, -0.000, second tertile; beta = -0.047, 95% CI: -0.085, -0.008, third tertile), and PCB-180 (beta = -0.041, 95% CI: -0.078, -0.005, third tertile). In female children, AGI was positively associated with maternal serum concentrations of PCB-101 (beta = 0.039, 95% CI: 0.002, 0.076, second tertile), and higher cord serum levels of 4,4'-DDT (beta = 0.032, 95% CI: 0.003, 0.061, third tertile) and 4,4'-DDE (beta = 0.040, 95% CI: 0.011, 0.069, third tertile). Conclusions: Our findings provide evidence of associations between specific POPs and AGI in boys and girls aged 4 years, and suggest that pre/perinatal exposure to POPs has a feminizing effect in males and a masculinizing effect in females.