The newborn metabolome: associations with gestational diabetes, sex, gestation, birth mode, and birth weight

Background Pathways towards many adult-onset conditions begin early in life, even in utero. Maternal health in pregnancy influences this process, but little is known how it affects neonatal metabolism. We investigated associations between pregnancy and birth factors and cord blood metabolomic profile in a large, population-derived cohort. Methods Metabolites were measured using nuclear magnetic resonance in maternal (28 weeks gestation) and cord serum from 912 mother-child pairs in the Barwon Infant Study pre-birth cohort. Associations between maternal (metabolites, age, BMI, smoking), pregnancy (pre-eclampsia, gestational diabetes (GDM)), and birth characteristics (delivery mode, gestational age, weight, infant sex) with 72 cord blood metabolites were examined by linear regression. Results Delivery mode, sex, gestational age, and birth weight were associated with specific metabolite levels in cord blood, including amino acids, fatty acids, and cholesterols. GDM was associated with higher cord blood levels of acetoacetate and 3-hydroxybutyrate. Conclusions Neonatal factors, particularly delivery mode, were associated with many cord blood metabolite differences, including those implicated in later risk of cardiometabolic disease. Associations between GDM and higher offspring ketone levels at birth are consistent with maternal ketosis in diabetic pregnancies. Further work is needed to determine whether these neonatal metabolome differences associate with later health outcomes. Impact Variations in blood metabolomic profile have been linked to health status in adults and children, but corresponding data in neonates are scarce. We report evidence that pregnancy complications, mode of delivery, and offspring characteristics, including sex, are independently associated with a range of circulating metabolites at birth, including ketone bodies, amino acids, cholesterols, and inflammatory markers. Independent of birth weight, exposure to gestational diabetes is associated with higher cord blood ketone bodies and citrate. These findings suggest that pregnancy complications, mode of delivery, gestational age, and measures of growth influence metabolic pathways prior to birth, potentially impacting later health and development.

Automated summary

This study explored the associations between pregnancy and birth factors and cord blood metabolomic profile in newborns, revealing that delivery mode, sex, gestational age, and birth weight are linked to specific metabolite levels in cord blood. Gestational diabetes was found to be associated with higher levels of certain metabolites in cord blood.