Prenatal Exposure to Artificial Light at Night and the Offspring’s First 1000-Day Growth: A Prospective Metabolomic and Gene-Environment Interaction Study

Our previous exposome study suggested associations between prenatal exposure to artificial light at night (ALAN) and offspring weight and fat growth during the first 1000 days. This study aims to further explore the underlying biomechanism and modifying effects of maternal genetic regulators. Among 1944 mother-child pairs from the Shanghai Birth Cohort, meet-in-the-middle, mediation, and enrichment analyses were combined with the early pregnancy untargeted metabolome to explore potential biological links between prenatal ALAN exposure and early life growth. Maternal polygenetic risk scores (PRS) for glucose- and lipid-metabolism-related phenotypes were constructed and dichotomized (high/low) to examine gene-environment interactions. We identified 35 mediating metabolites between prenatal ALAN exposure and growth outcomes, which were enriched in neural signal transduction-related pathways and associated with the circadian rhythm. The effects of ALAN exposure on fetal and child growth were more pronounced among mothers with high PRS levels for fasting glucose, HbA1c, and triglycerides. To sum up, prenatal ALAN exposure may be associated with reduced weight and adiposity gains during the first 1000 days. These associations may be partly explained by disturbances in maternal circadian rhythms and appeared more pronounced among mothers with high genetic predispositions to glucose and triglyceride levels.