ABSTRACT
Background & Aims: Scarce knowledge about the impact of metabolism-disrupting chemicals (MDCs) on steatotic liver disease limits opportunities for intervention. We evaluated pregnancy MDC-mixture associations with liver outcomes, and effect modification by folic acid (FA) supplementation in mother-child pairs.
Methods: We studied 200 mother-child pairs from the Mexican PROGRESS cohort, with 43 MDCs measured during pregnancy (estimated air pollutants, blood/urine metals or metalloids, urine high- and low-molecular-weight phthalate [HMWPs, LMWPs] and
organophosphate-pesticide metabolites), and serum liver enzymes (ALT, AST) at 9 years post-parturition. Outcomes included elevated liver enzymes in children and established clinical scores for steatosis and brosis in mothers (i.e., AST:ALT, FLI, HSI, FIB-4). Bayesian-weighted quantile sum regression assessed MDC-mixture associations with liver outcomes. We further examined chemical-chemical interactions and effect modi cation by self-reported FA supplementation.
Results: In children, many MDC-mixtures were associated with liver injury. Per quartile HMWP-mixture increase, ALT increased by
10.1% (95% CI 1.67%, 19.4%) and AST by 5.27% (95% CI 0.80%, 10.1%). LMWP-mixtures and air pollutant-mixtures were
associated with higher AST and ALT, respectively. Air pollutant and non-essential metal/element associations with liver enzymes
were attenuated by maternal cobalt blood concentrations (p-interactions <0.05). In mothers, only the LMWP-mixture was associated with odds for steatosis (odds ratio = 1.53, 95% CI 1.01–2.28 for HSI >36, and odds ratio 1.62, 95% CI 1.05–2.49 for AST:ALT <1). In mothers and children, most associations were attenuated (null) at FA supplementation >−600 lg/day (p-interactions <0.05).
Conclusions: Pregnancy MDC exposures may increase risk of liver injury and steatosis, particularly in children. Adequate FA supplementation and maternal cobalt levels may attenuate these associations.