Prenatal exposure to mixtures of persistent endocrine-disrupting chemicals and birth size in a population-based cohort of British girls

By Kristin J Marks, Penelope P Howards, Melissa M Smarr, W Dana Flanders, Kate Northstone, Johnni H Daniel, Andreas Sjödin, Antonia M Calafat, and Terryl J Hartman
March 24, 2021
DOI: 10.1097/EDE.0000000000001351


Previous studies of endocrine-disrupting chemicals have examined one of these chemicals at a time in association with an outcome; studying mixtures better approximates human experience. We investigated the association of prenatal exposure to mixtures of persistent endocrine disruptors [per- and polyfluoroalkyl substances (PFAS), polychlorinated biphenyls (PCBs), and organochlorine pesticides] with birth size among female offspring in the Avon Longitudinal Study of Parents and Children (ALSPAC), based in the United Kingdom in 1991-1992.


We quantified concentrations of 52 endocrine-disrupting chemicals in maternal serum collected during pregnancy at median 15 weeks' gestation. Birth weight, crown-to-heel length, and head circumference were measured at birth; ponderal index and small for gestational age were calculated from these. We used repeated holdout weighted quantile sum regression and Bayesian kernel machine regression to examine mixtures in 313 mothers.


Using weighted quantile sum regression, all mixtures (each chemical class separately and all three together) were inversely associated with birth weight. A one-unit increase in WQS index (a one-decile increase in chemical concentrations) for all three classes combined was associated with 55 g (β: -55 g, 95% CI: -89, -22 g) lower birth weight. Associations were weaker but still inverse using Bayesian kernel machine regression. Under both methods, PFAS were the most important contributors to the association with birth weight. We also observed inverse associations for crown-to-heel length.


These results are consistent with the hypothesis that prenatal exposure to mixtures of persistent endocrine-disrupting chemicals affects birth size.

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