Association between the Early-Life Exposome and Birth Weight

Abstract

Background: Several environmental contaminants have been identified as possibly influencing birth weight, mainly from single exposure studies. The Exposome paradigm offers perspectives to avoid selective reporting of findings and to control for confounding by co-exposures. Aim: To assess the association of the pregnancy exposome with birth weight. Methods: Within HELIX exposome project, 131 prenatal exposures, several of which had some a priori plausibility for an effect on fetal growth, were assessed using biomarkers and environmental models in 1,301 pregnant women from six European cohorts. Associations were assessed using deletion-substitution-addition (DSA) algorithm, which considers all exposures simultaneously, and exposome-wide association study (ExWAS), which considers them independently. We tested for pairwise interactions and corrected exposures for exposure misclassification through regression calibration. Results: Lead (median, 9.7 µg/l; interquartile range, IQR, 6.0 µg/l) was the only exposure associated with birth weight in the DSA model corrected for exposure misclassification (mean birth weight change for an IQR increase, -48 g, 95% confidence interval, -90; -6). No exposure passed the significance threshold of ExWAS corrected for multiple testing; the exposures most strongly associated with birth weight in ExWAS were lead (-48 g, 95% CI, -90; -6), fine particulate matter (PM2.5) absorbance in the third pregnancy trimester (-50 g; -94; -6) and PM2.5 concentration in the third trimester (-33 g, 95% CI, -66, -1). There was no strong evidence of order-two interaction. Conclusions: Our study is one of the largest considering over 100 environmental exposures for effects on birth weight. Compared to single exposure studies, our Exposome approach allowed identifying exposures associated with birth weight while making all tests explicit, correcting for confounding by co-exposures, for exposure misclassification and considering interactions between exposures.