Maternal body mass index, early-pregnancy metabolite profile and birthweight.

CONTEXT Maternal prepregnancy BMI has a strong influence on gestational metabolism, but detailed metabolic alterations are unknown. OBJECTIVE First, to examine the associations of maternal prepregnancy BMI with maternal early-pregnancy metabolite alterations. Second, to identify an early-pregnancy metabolite profile associated with birthweight in women with a higher prepregnancy BMI that improved prediction of birthweight compared to glucose and lipid concentrations. DESIGN, SETTING AND PARTICIPANTS Prepregnancy BMI was obtained in a subgroup of 682 Dutch pregnant women from the Generation R prospective cohort study. MAIN OUTCOME MEASURES Maternal non-fasting targeted amino acid, non-esterified fatty acid, phospholipid and carnitine concentrations measured in blood serum at mean gestational age of 12.8 weeks. Birthweight, obtained from medical records. RESULTS A higher prepregnancy BMI was associated with 72 altered amino acid, non-esterified fatty acid, phospholipid and carnitine concentrations and 6 metabolite ratios reflecting Krebs cycle, inflammatory, oxidative stress and lipid metabolic processes (p-values<0.05). Using penalized regression models, a metabolite profile was selected including 15 metabolites and 4 metabolite ratios, based on its association with birthweight in addition to prepregnancy BMI. The adjusted R 2 of birthweight was 6.1% for prepregnancy BMI alone, 6.2% after addition of glucose and lipid concentrations and 12.9% after addition of the metabolite profile. CONCLUSIONS A higher maternal prepregnancy BMI was associated with altered maternal early-pregnancy amino acids, non-esterified fatty acids, phospholipids and carnitines. Using these metabolites, we identified a maternal metabolite profile which improved prediction of birthweight in women with a higher prepregnancy BMI compared to glucose and lipid concentrations.