Phthalate and bisphenol exposure in relation to infant reproductive development during minipuberty

New York University School Of Medicine, New York NY

Investigators

Abstract

Project Summary/Abstract Minipuberty, a brief window during the first six months of life when reproductive hormones surge, may be a particularly vulnerable period for endocrine disruption by phthalates and bisphenols, endocrine-disrupting chemicals (EDCs) with both estrogenic and anti-androgenic activity that infants are highly exposed to via disposable diapers, wipes, baby lotions, shampoos, and plastic baby bottles. Exposure to EDCs during critical periods of early development can alter ovarian and testicular tissue, which may influence future reproductive development and function, including timing of pubertal maturation and subsequent fecundity. To date, only three cross-sectional studies have examined endocrine disruption during minipuberty, and while results have differed, all have found some associations between bisphenols and/or phthalates and infant reproductive hormones. None has examined associations between EDC exposure during minipuberty and anogenital distance (AGD), a measure that has been associated with maternal prenatal bisphenol and phthalate levels as well as adult reproductive health outcomes. The current project, nested within the New York University Children’s Health and Environment Study (NYU CHES), an ongoing prospective birth cohort, will include 480 full-term singleton infants whose mothers have provided repeated urine samples during pregnancy and examine both in utero and concurrent chemical exposure in relation to hormones and AGD in minipuberty. During 2 and 4-month postnatal study visits, urine and blood will be collected from the infants, and urine and breast milk will be collected from their mothers. Infant AGD will be measured by trained study staff members at birth and during both postnatal study visits. Maternal prenatal urine, child postnatal urine, and maternal breast milk will be screened for bisphenols and phthalates. Unlike prior studies that have focused only on chemicals for which analytic standards are available, we will examine both known and unknown bisphenols and phthalates using a novel approach that will leverage advanced computational methods for analyzing non-targeted high-resolution mass spectrometry (HRMS) data. Concentrations of nine reproductive hormones and two proteins will be quantified in infant serum via high performance liquid chromatography-electrospray ionization-tandem mass spectrometry. Aims include: 1) evaluating longitudinal associations of maternal prenatal urinary bisphenol and phthalate levels with infant reproductive hormone concentrations during minipuberty, 2) quantifying associations of infant urinary bisphenol and phthalate levels with infant reproductive hormone concentrations during minipuberty, and 3) examining joint effects of infant chemical and hormone levels on AGD during minipuberty. We hypothesize that phthalate and bisphenol exposure during both prenatal and postnatal periods will be associated with infant reproductive hormones, that both chemicals and hormones will be associated with AGD, and that associations will be sexually dimorphic. Regression analyses will incorporate advanced statistical methods for the reduction of high- dimensional data and for analyzing effects of chemical mixtures.