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Importance: Prenatal exposures to endocrine-disrupting chemicals (EDCs) may increase the risk for liver injury in children; however, human evidence is scarce, and previous studies have not considered potential EDC-mixture effects. Furthermore, the association between prenatal EDC exposure and hepatocellular apoptosis in children has not been studied previously. Objective: To investigate associations of prenatal exposure to EDC mixtures with liver injury risk and hepatocellular apoptosis in childhood. Design, Setting, and Participants: This prospective cohort study used data collected from April 1, 2003, to February 26, 2016, from mother-child pairs from the Human Early-Life Exposome project, a collaborative network of 6 ongoing, population-based prospective birth cohort studies from 6 European countries (France, Greece, Lithuania, Norway, Spain, and the UK). Data were analyzed from April 1, 2021, to January 31, 2022. Exposures: Three organochlorine pesticides, 5 polychlorinated biphenyls, 2 polybrominated diphenyl ethers (PBDEs), 3 phenols, 4 parabens, 10 phthalates, 4 organophosphate pesticides, 5 perfluoroalkyl substances, and 9 metals. Main Outcomes and Measures: Child serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyltransferase (GGT), and CK-18 were measured at 6 to 11 years of age. Risk for liver injury was defined as having ALT, AST, and/or GGT levels above the 90th percentile. Associations of liver injury or cytokeratin 18 (CK-18) levels with each chemical group among the 45 EDCs measured in maternal blood or urine samples collected in pregnancy were estimated using 2 complimentary exposure-mixture methods: bayesian weighted quantile sum (BWQS) and bayesian kernel machine regression. Results: The study included 1108 mothers (mean SD age at birth, 31.0 4.7 years) and their singleton children (mean SD age at liver assessment, 8.2 1.6 years; 598 54.0% boys). Results of the BWQS method indicated increased odds of liver injury per exposure-mixture quartile increase for organochlorine pesticides (odds ratio OR, 1.44 95% credible interval (CrI), 1.21-1.71), PBDEs (OR, 1.57 95% CrI, 1.34-1.84), perfluoroalkyl substances (OR, 1.73 95% CrI, 1.45-2.09), and metals (OR, 2.21 95% CrI, 1.65-3.02). Decreased odds of liver injury were associated with high-molecular-weight phthalates (OR, 0.74 95% CrI, 0.60-0.91) and phenols (OR, 0.66 95% CrI, 0.54-0.78). Higher CK-18 levels were associated with a 1-quartile increase in polychlorinated biphenyls (β, 5.84 95% CrI, 1.69-10.08 IU/L) and PBDEs (β, 6.46 95% CrI, 3.09-9.92 IU/L). Bayesian kernel machine regression showed associations in a similar direction as BWQS for all EDCs and a nonlinear association between phenols and CK-18 levels. Conclusions and Relevance: With a combination of 2 state-of-the-art exposure-mixture approaches, consistent evidence suggests that prenatal exposures to EDCs are associated with higher risk for liver injury and CK-18 levels and constitute a potential risk factor for pediatric nonalcoholic fatty liver disease.
Midya et al. (2022) studied this question.