The associations between prenatal exposure to organophosphate esters and children's anogenital distance growth trajectory: A birth cohort study.

Reproductive toxicity of organophosphate esters (OPEs) has been reported, and some animal and human studies suggest that prenatal OPE exposure may alter anogenital distance (AGD) in offspring. However, the long-term effects of prenatal OPE exposure on AGD growth trajectory remain unclear. Based on the Shanghai-Minhang Birth Cohort Study, we examined the effects of prenatal OPE exposure on AGD growth trajectory of children from birth to 48 months. Urine samples from pregnant women were analyzed for eight OPE metabolites. AGD was measured at birth, 6, 12, and 48 months (boys: AGDAP (anus-penis) and AGDAS (anus-scrotum); girls: AGDAC (anus-clitoris) and AGDAF (anus-fourchette)). Group-Based Trajectory Modeling identified two trajectory groups of AGDAC, AGDAF, and AGDAS, which were named as "fast growth" and "slow growth" groups, respectively. Modified Poisson regression models showed a general pattern that higher prenatal OPE exposure increased the probability of AGD being in the "slow growth" trajectory group in both sexes. Statistically or marginally significant associations were found for bis(2-butoxyethyl) phosphate (BBOEP), bis(2-ethylhexyl) phosphate (BEHP), aryl-OPEs, and alkyl-OPEs in girls, and bis(1-chloro-2-propyl) phosphate (BCIPP) and tricresyl phosphate (DCP) in boys. Bayesian Kernel Machine Regression models showed similar results, with significant associations only found in girls, where alkyl-OPEs (especially BBOEP) were identified as major contributors. This study presents the first human evidence of the long-term effects of prenatal OPE exposure on the growth trajectory of AGD, with the magnitude of effects varying by OPE substituents.