Prenatal Exposure to Perfluoroalkyl Substances Associated With Increased Susceptibility to Liver Injury in Children

Nikos Stratakis, David Conti, Ran Jin, Katerina Margetaki, Damaskini Valvi, Alexandros P. Siskos, Lea Maitre, Erika Garcia, Nerea Varo, Yinqi Zhao, Theano Roumeliotaki, Marina Vafeiadi, Jose Urquiza, Silvia Fernandez-Barres, Barbara Heude, Xavier Basagana, Maribel Casas, Serena Fossati, Regina Grazuleviciene, Sandra AndrusaityteKaran Uppal, Rosemary Rc McEachan, Eleni Papadopoulou, Oliver Robinson, Line Smastuen Haug, John Wright, Miriam B. Vos, Hector C. Keun, Martine Vrijheid, Kiros T. Berhane, Rob McConnell, Lida Chatzi*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

34 Citations (Web of Science)

Abstract

Background and Aims Per- and polyfluoroalkyl substances (PFAS) are widespread and persistent pollutants that have been shown to have hepatotoxic effects in animal models. However, human evidence is scarce. We evaluated how prenatal exposure to PFAS associates with established serum biomarkers of liver injury and alterations in serum metabolome in children. Approach and Results We used data from 1,105 mothers and their children (median age, 8.2 years; interquartile range, 6.6-9.1) from the European Human Early-Life Exposome cohort (consisting of six existing population-based birth cohorts in France, Greece, Lithuania, Norway, Spain, and the United Kingdom). We measured concentrations of perfluorooctane sulfonate, perfluorooctanoate, perfluorononanoate, perfluorohexane sulfonate, and perfluoroundecanoate in maternal blood. We assessed concentrations of alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyltransferase in child serum. Using Bayesian kernel machine regression, we found that higher exposure to PFAS during pregnancy was associated with higher liver enzyme levels in children. We also measured child serum metabolomics through a targeted assay and found significant perturbations in amino acid and glycerophospholipid metabolism associated with prenatal PFAS. A latent variable analysis identified a profile of children at high risk of liver injury (odds ratio, 1.56; 95% confidence interval, 1.21-1.92) that was characterized by high prenatal exposure to PFAS and increased serum levels of branched-chain amino acids (valine, leucine, and isoleucine), aromatic amino acids (tryptophan and phenylalanine), and glycerophospholipids (phosphatidylcholine [PC] aa C36:1 and Lyso-PC a C18:1). Conclusions Developmental exposure to PFAS can contribute to pediatric liver injury.

Original languageEnglish
Pages (from-to)1758-1770
Number of pages13
JournalHepatology
Volume72
Issue number5
Early online date19 Oct 2020
DOIs
Publication statusPublished - Nov 2020

Keywords

  • PERFLUOROOCTANOIC ACID
  • SERUM
  • PFOA
  • ADOLESCENTS
  • HOMEOSTASIS
  • POPULATION
  • METABOLISM
  • BIOMARKERS
  • STEATOSIS
  • CHEMICALS

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