Maternal metabolic signatures at early gestation associated with birth weight and neurodevelopment in early childhood.

BACKGROUND

Emerging evidence suggests that maternal factors during pregnancy can exert effects on offspring. However, the underlying metabolic associations remain insufficiently understood.

METHODS

We investigated associations between first-trimester maternal metabolic profiles and offspring development with large-scale untargeted metabolomics in the prospective Shanghai Birth Cohort (N = 1158). Birth weight and cognitive scores at age four assessed with the Wechsler Preschool and Primary Scale of Intelligence were used as short- and long-term developmental indicators.

RESULTS

Here we show maternal fatty acid and phospholipid metabolism in early pregnancy is significantly associated with birth weight. Carnitine, LPE 18:2, and LPG O-13:1 are negatively associated with birth weight, whereas PC 32:2, glycerophosphocholine and several fatty acids show significant positive associations. Several dipeptides have positive associations with cognitive outcomes, while many fatty acids and N-acylethanolamines are negatively associated. Among the six cognitive indices, verbal comprehension has the most metabolite associations, with 4-pyridoxic acid, 1-methylxanthine, and phenylalanyltryptophan being most strongly linked. 4-Pyridoxic acid, a vitamin B6 metabolite, significantly mediates the positive association between multivitamin intake and cognitive development. Several metabolites show sex-specific associations with offspring development, which is consistent with the known sex-related differences in early childhood developmental patterns.

CONCLUSIONS

Maternal metabolism in early pregnancy is associated with birth weight and long-term cognitive development in offspring. As maternal metabolic profiles reflect both genetic and environmental influences, many metabolites mediate maternal influences on development and reflect sex-specific patterns in child growth.