Association of phthalate and substitute exposure with gestational liver function: A longitudinal cohort study

Environmental chemical exposures may impair hepatic function during pregnancy. This study aimed to longitudinally assess the association between phthalate/substitute exposure and liver function parameters during pregnancy.

Within the Wuhan Healthy Baby Birth Cohort (2014-2017), we quantified 19 metabolites (8 of phthalates and 11 of their substitutes) in 1,623 urine samples from 541 pregnant women across all three trimesters and measured 13 liver function indices in late pregnancy. We employed generalized linear models (GLM) for association analyses of the outcomes with pregnancy-averaged exposures, generalized estimating equations (GEE) for trimester-specific exposures, and Bayesian kernel machine regression (BKMR) and weighted quantile sum (WQS) for mixture effects.

The GLM showed that higher pregnancy-averaged concentrations of traditional phthalates, including monobutyl phthalate (MBP) and mono (2-ethly-5-carboxypentyl) phthalate (MECPP), were significantly associated with higher alkaline phosphatase (ALP) levels. The metabolites of diisononyl phthalate (DiNP) were also associated with elevated ALP. However, inverse associations were observed between pregnancy-averaged concentrations of traditional phthalates (monoethyl phthalates [MEP] and monomethyl phthalate [MMP]) and protein biomarkers (prealbumin [PA] and total protein [TP]). Trimester-specific GEE models yielded similar associations. Both BKMR and WQS models showed a significant joint effect of the phthalate mixture on reduced PA, with MEP and MMP identified as the primary contributors.

Our findings suggest that exposure to phthalates and their substitutes may adversely affect liver function during pregnancy, highlighting the need to consider the hepatotoxicity of emerging substitutes.