Prenatal exposure to lipophilic endocrine-disrupting chemicals and liver injury in children using chemical mixture approaches

Abstract

BACKGROUND AND AIM: Exposure to Endocrine Disrupting Chemicals (EDC) may increase liver injury, but few studies have examined these associations in children and most focused on a single chemical group. We evaluated the associations between a wide range of prenatal EDC exposures and child liver injury. METHODS: We studied 1108 healthy children from the Human Early-Life Exposome (HELIX) project, a collaborative network of six established longitudinal population-based birth cohort studies in Europe. Thirty lipophilic EDCs (including 3 organochlorine pesticides, 5 polychlorinated-biphenyl, 2 polybrominated-diphenyl-ethers [PBDEs], 5 high molecular weight phthalates (HMWP), 5 low molecular weight phthalates, 6 phenols and 4 organophosphate pesticides) were measured in maternal pregnancy blood or urine. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT) and cytokeratin 18 (CK18) were measured in child serum at follow-up between age 6-11 years. Liver injury was defined as having any liver enzyme (ALT, AST or GGT) above the 90th percentile. We used Bayesian generalized linear mixed regressions (Bglmr) to estimate associations of individual chemicals, Bayesian Weighted Quantile Sum (BWQS) and Bayesian Kernel Machine Regression (BKMR) to assess the overall association of each chemical group with liver injury and CK18, adjusting for confounders. RESULTS:BWQS results indicated that organochlorine pesticides and PBDEs were associated with increased odds of liver injury (OR[95%CI] by chemical mixture quartile increase=1.44[1.23, 1.72] and 1.59[1.37, 1.90], respectively); whereas HMWP were associated with decreased odds of liver injury (OR[95%CI]=0.71[0.59, 0.85]). A quartile increase of PBDEs was positively associated with CK18 (Estimate[95%CI]=5.33 Units/Liter [2.52,8.16]). Bglmr and BKMR showed associations in same direction as the BWQS results. There was evidence of effect heterogeneity by sex for organochlorine pesticides and HMWPs with liver injury status. CONCLUSIONS:Using multiple chemical mixture approaches we found that prenatal exposures to persistent pollutants, especially to organochlorine compounds, and PBDEs, may be associated with increased risk for liver injury in childhood. KEYWORDS: Chemical exposures, Endocrine disrupting chemicals, Mixtures analysis, Modeling, Environmental epidemiology