Association Between the Pregnancy Exposome and Fetal Growth

Abstract

Background: Several environmental contaminants were reported to possibly influence fetal growth, generally from single exposure family studies, which are prone to publication bias. The exposome paradigm offers perspectives to avoid selective reporting of findings and to control for confounding by co-exposures. Objectives: We aimed to assess the association of the pregnancy chemical and external exposomes with fetal growth. Methods: Within HELIX project, 131 prenatal exposures were assessed using biomarkers and environmental models in 1,287 mother-child pairs from six European cohorts. We investigated their associations with fetal growth using a deletion-substitution-addition (DSA) algorithm considering all exposures simultaneously, and an exposome-wide association study (ExWAS) considering each exposure independently. We corrected for exposure misclassification, and tested for exposure-exposure and sex-exposure interactions. Findings: Lead blood level was the only exposure associated with fetal growth in the DSA model (97g weight decrease for each doubling in lead concentration). No exposure passed the multiple testing-corrected significance threshold of ExWAS; without multiple testing correction, this model was in favor of a negative association of fine particulate matter concentration with birth weight; and of a positive sex-specific association of parabens with birth weight in boys only. No two-way interaction between exposure variables was identified. Interpretation: This first large-scale exposome study of fetal growth simultaneously considered over 100 environmental exposures. Compared to single exposure studies, our approach allowed making all tests (usually reported in successive publications) explicit. Lead exposure is still a health concern in Europe and parabens health effects warrant further investigation. Funding Statement: FP7/2007-2013, HELIX project (no 308333). Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: The study was approved by the relevant ethical committees from each country and an informed consent form was assigned from all participants, or the parents of the children.