Associations of endocrine disrupting chemicals with anogenital distance across infancy.

Abstract

Pregnant women are ubiquitously exposed to endocrine disrupting chemicals (EDCs). Anogenital distance (AGD) is a hormone-dependent marker of reproductive system development. We evaluated associations of maternal EDCs with infant AGD at birth and mini-puberty (5-months), and AGD growth across infancy. Pregnant women enrolled in I-KIDS (Illinois Kids Development Study) - an observational longitudinal study (2013-2019). Participants were recruited from two OBGyn clinics in Champaign-Urbana, IL. This study includes 563 mother/infant pairs at birth and 5-months of age. We measured ten phthalates/replacements and nine phenols in five pooled first-morning urine samples collected across pregnancy. In newborns and 5-month-olds, we divided short and long AGD measures by body length (termed anogenital index, AGI) and calculated %AGI growth across infancy. We evaluated covariate-adjusted associations of phthalates/replacements or phenols separately (quantile g-computation) or combined (hierarchical Bayesian kernel machine regression), with AGI measures. Associations of phthalates/replacements with newborn AGI in females and phenols in males were inconsistent. However, in 5-month-old females, each quartile increase in the phthalate/replacement mixture was associated with -4.13mm/m shorter AGIShort (95% confidence interval (CI): -7.22, -1.05), -3.89mm/m shorter AGILong (95%CI: -7.55, -0.23), -39.49% less AGIShort growth (95%CI: -62.44, -16.54), and -8.78% less AGILong growth (95%CI: -16.06, -1.51); associations with AGILong growth were strongest at lower mixture quantiles. AGD in mini-puberty and growth across infancy may reflect EDC-mediated hormonal disruption in utero, particularly in females, supporting the need to investigate these markers as predictors of long-term reproductive health.