Cord blood metabolic signatures of birthweight: a population based study

Birthweight is an important indicator of maternal and fetal health, and a predictor of health in later life. However, the determinants of variance in birthweight are still poorly understood. We aimed to identify the biological pathways, which may be perturbed by environmental exposures, that are important in determining birthweight. We applied untargeted mass-spectrometry based metabolomics to 481 cord blood samples collected at delivery in four birth cohorts from across Europe: ENVIRONAGE (Belgium), INMA (Spain), Piccolipiu (Italy) and Rhea (Greece). We performed a metabolome-wide association scan for birthweight on over 4000 metabolic features, controlling the false discovery rate at 5%. Annotation of compounds was conducted through reference to authentic standards. We identified 68 metabolites significantly associated with birthweight, including vitamin A, progesterone, docosahexaenoic acid, indolelactic acid, and multiple acylcarnitines and phosphatidylcholines. We observed enrichment (p < 0.05) of the tryptophan metabolism, prostaglandin formation, C21-steroid hormone signalling, carnitine shuttle and glycerophospholipid metabolism pathways. Vitamin A was associated with both maternal smoking and birthweight, suggesting a mediation pathway. Our findings shed new light on the pathways central to fetal growth and will have implications for antenatal and perinatal care and potentially for health in later life