Prenatal Exposure to Endocrine-Disrupting Chemicals Increases Risk of Liver Injury

Vishal Midya, PhD, MStat

Prenatal exposure to certain endocrine-disrupting chemicals (EDC) could increase the risk of developing liver injuries later in life, according to new research based in Europe.

A team, led by Vishal Midya, PhD, MStat, Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, investigated the link between prenatal exposure to endocrine-disrupting chemical mixtures with the risk of liver injuries and hepatocellular apoptosis in pediatric patients.

Prenatal Exposure

Prenatal exposure to endocrine-disrupting chemicals is a known risk factor for liver injuries in pediatric patients, but the link between prenatal exposure and hepatocellular apoptosis has not yet been examined.

In the prospective cohort study, the investigators collected data between April 1, 2003 and February 26, 2016 of mother-child pairs from the Human Early-Life Exposome project, a collaborative network of 6 ongoing, population-based prospective birth cohort trials in France, Greece, Lithuania, Norway, Spain, and the UK.

The investigators looked at various exposures as well, including 3 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.

The team also sought main outcomes of child serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyltransferase (GGT), and cytokeratin 18 (CK-18) were measured at 6-11 years of age.

They defined the risk of liver injury as having ALT, AST, and/or GGT levels above the 90th percentile. In addition, they defined the associations of liver injury or CK-18 levels with each chemical among the 45 EDCs measured in maternal blood or urine samples collected in pregnancy with Bayesian weighted quantile sum (BWQS) and Bayesian kernel machine regression.

Overall there were 1108 mothers with a mean age at birth of 31 years included in the study with their singleton children. The mean age of the pediatric patients at their liver assessment was 8.2 years.

The Risk of Liver Injury

The BWQS method showed an increased odds of liver injury per exposure-mixture quartile increase for organochlorine pesticides (OR, 1.44; 95% 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).

There were also decreased odds of liver injury linked to high-molecular-weight phthalates (OR, 0.74; 95% CrI, 0.60-0.91) and phenols (OR, 0.66; 95% CrI, 0.54-0.78).

The results also show that higher CK-18 levels were associated with a 1-quartile increase in polychlorinated biphenyls (β, 5.84 IU/L; 95% CrI, 1.69-10.08 IU/L) and PBDEs (β, 6.46 IU/L; 95% CrI, 3.09-9.92 IU/L).

The Bayesian kernel machine regression results show associations in a similar direction as BWQS for all EDCs. The Bayesian kernel machine regression also showed a nonlinear association between phenols and CK-18 levels.

“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,” the authors wrote.

The study, “Association of Prenatal Exposure to Endocrine-Disrupting Chemicals With Liver Injury in Children,” was published online in JAMA Network Open.