# Developmental origins of child liver injury: Effects of prenatal environmental exposures

> **NIH NIH R21** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2020 · $191,949

## Abstract

ABSTRACT
Emerging experimental evidence indicates that exposure to environmental pollutants causes liver injury and
contributes to “toxicant-associated fatty liver disease”, specially if exposure occurs during critical stages of
development. Animal studies show hetatotoxic effects even at low levels of exposure to many endocrine
disrupting chemicals (EDCs), including persistent organic pollutants, plasticizers and certain metals. Moreover,
chronic exposures to ambient fine particulate matter have been shown to induce liver steatosis, inflammation
and fibrosis in mice, accompanied by elevated blood liver enzymes. Human studies have largely been cross-
sectional, and no previous population study has examined associations of in utero exposure to air pollution and
EDCs with subsequent pediatric liver injury. We propose a novel analytyical approach for investigating effects of
in utero environmental exposures on child liver injury, leveraging the extraordinary existing resources of the
“Human Early Life Exposome (HELIX)” project, which provides completely harmonized biomonitoring data on
environmental exposures, geospatial data and omics biomarkers in 1200 pregnant mothers and their children
followed longitudinally up to the age of 6-10 years in 6 European countries. We hypothesize that higher
ambient air pollution and targeted EDC exposures during pregnancy are associated with subsequent
child liver injury and associated dysregulation of metabolic and inflammatory pathways. We propose to
measure in archived serum samples established clinical biomarkers of child liver injury. We will apply novel
statistical methods to conduct integrated analyses of HELIX chemical exposures, endogenous metabolites,
cytokines, adipokines, and established clinical liver injury biomarkers, with the goal of identifying latent variables
representing distinct groups of children at risk for liver injury. Our specific aims are: 1: To evaluate the
associations of pregnancy trimester-specific fine particle and other regulated air pollution exposures with
biomarkers of child liver injury. 2: To evaluate the associations of prenatal exposure to targeted EDCs with
biomarkers of child liver injury. 3: To assess associations of prenatal environmental exposures with biological
distinct subgroups of children at risk for liver injury, using an innovative latent variable approach that integrates
exposure profiles, clinical biomarkers, engogenous metabolites, cytokine and adipokine data. The proposal
brings together international experts on environmental epidemiology, pediatric hepatology, omics, and
biostatistics from different research institutes in the U.S. and Europe and will be the first study to link multiple
prenatal environmental exposures with childhood liver injury outcomes. The study is cost efficient, leveraging a
large European investment in HELIX, and has potential to advance our understanding of early life environmental
contributions to child liver injury and to identify ne...

## Key facts

- **NIH application ID:** 9922274
- **Project number:** 5R21ES029681-02
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** VAIA LIDA CHATZI
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $191,949
- **Award type:** 5
- **Project period:** 2019-05-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9922274

## Citation

> US National Institutes of Health, RePORTER application 9922274, Developmental origins of child liver injury: Effects of prenatal environmental exposures (5R21ES029681-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9922274. Licensed CC0.

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