Metabolites co-correlating with maternal obesity and gestational weight gain and offspring childhood obesity: a prospective birth cohort study

Background: Elevated prepregnancy body mass index (ppBMI) and excessive gestational weight gain (GWG) may contribute to the development of childhood overweight or obesity (COWO), potentially by altering the intrauterine metabolic environment. Objectives: This study aimed to evaluate the impact of maternal obesity phenotypes on maternal and umbilical cord blood metabolomic profiles, both individually and collectively, and to further examine their association with COWO incidence from preschool through adolescence. Methods: We analyzed 1253 mother–child dyads with maternal metabolomic data collected 1 to 3 d postpartum and 856 dyads with cord metabolomic data from a prospective multiethnic birth cohort. Metabolomics was profiled using liquid chromatography–tandem mass spectrometry. COWO was defined as a BMI ≥ 85th percentile for a specific age and sex. Metabolomic signatures of maternal obesity and scores were derived using linear regression and elastic net regression, and their associations with COWO were assessed via logistic regression. Results: Most maternal metabolites were significantly correlated with corresponding cord metabolites (Spearman’s ρ: 0.11–0.67; adjusted P < 0.05), except for steroids and certain phospholipids. ppBMI was significantly associated with broad-based alterations in maternal metabolite profiles, particularly medium-chain acylcarnitines, saturated sphingomyelins, triacylglycerols, and phospholipids carrying PUFAs. We further developed ppBMI-related multi-metabolite scores (Pearson’s r = 0.43–0.64) that were associated with higher birthweight (β = 0.07–0.11; P < 0.013) and increased COWO risk (odds ratio: 1.18–1.61; all P < 0.05) from preschool through adolescence. A similar pattern was observed for GWG. In mediation analyses, the maternal metabolite score explained 12.3% (95% confidence interval: 2.18, 24.5; P = 0.02) of the association between ppBMI and BMI z-score at the last well-child visit. Conclusions: Metabolomic profiles are associated with and may partly mediate the association between maternal obesity, particularly ppBMI, and an increased risk of COWO. These findings warrant validation in independent cohorts.