Cord Blood Metabolic Signatures of Birth Weight: A Population-Based Study

Birth
weight is an important indicator of maternal and fetal health
and a predictor of health in later life. However, the determinants
of variance in birth weight are still poorly understood. We aimed
to identify the biological pathways, which may be perturbed by environmental
exposures, that are important in determining birth weight. 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 birth weight 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 birth weight, 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 signaling, carnitine shuttle, and glycerophospholipid
metabolism pathways. Vitamin A was associated with both maternal smoking
and birth weight, 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.