Associations of maternal exposure to nonylphenol and bisphenols with precocious puberty in girls: A nested case-control study.

Few studies have explored the association of prenatal exposure to typical endocrine disrupting chemicals such as nonylphenol (NP) and bisphenols with the odds of precocious puberty (PP) in girls. To evaluate the associations of maternal exposure to NP and bisphenols during pregnancy with the odds of PP [including central PP (CPP) and incomplete PP (IPP) subtypes] in girls, this study included 87 CPP cases, 109 IPP cases, and 588 matched (1: 3) controls based on a Wuhan birth cohort (2012-2014). Maternal urinary concentrations of three bisphenols and two NP metabolites [including oxo-NP and hydroxy-NP (OH-NP)] were measured before delivery. Multivariable logistic regression and weighted quantile sum regression were applied to evaluate the relationships of the individual phenols and their mixture with the PP odds in the girls. Non-linear dose-response relationships were observed between oxo-NP and OH-NP and the PP odds (p for non-linearity <0.05). Specifically, after false discovery rate (FDR) correction, the third quartile of OH-NP [odds ratio (OR): 1.42, 95 % confidence interval (CI): 1.09-1.87; pFDR = 0.01] and oxo-NP (OR: 1.52, 95 % CI: 1.17-1.98; pFDR = 0.002) showed significant associations with the overall PP odds. For PP subtypes, oxo-NP was significantly associated with CPP (the third quartile OR: 1.77, 95 % CI: 1.17-2.68; pFDR = 0.04). NP metabolites were identified as the major contributors to the phenol mixture associated with the CPP odds. Prenatal NP exposure may non-linearly increase the odds of PP in girls, particularly that of CPP, at moderate exposure levels, underscoring the need to reduce prenatal exposure and clarify the underlying mechanisms.