Maternal obesity poses significant risks to fetal health, influencing metabolomic profiles in newborn cord blood. Despite the growing application of metabolomics, limited research has explored how BMI-associated metabolite alterations may vary across different ethnic groups. We analyzed metabolomic data from a multi-ethnic cohort of 87 participants, including Native Hawaiian and Pacific Islander (NHPI) individuals. We used an ensemble machine learning model with a meta-learner to predict cord blood metabolomic changes associated with maternal BMI, the continuous obesity metric. The meta-learner integrated linear and nonlinear approaches and achieved significantly enhanced performance compared to the baseline linear regression model. In cord blood samples, glycine, serine, and threonine metabolism are activated by maternal obesity, while fatty acid biosynthesis and biosynthesis of unsaturated fatty acids are repressed. Some metabolites associated with these pathways show ethnicity-specific patterns. Compared to Asians and caucasians, 1,5-anhydrosorbitol, glycine, L-threonine show a unique increase from normal to obese maternally associated groups in NHPI, while PC(O-44:6) is significantly decreased in NHPI. The finding reveals the impact of maternal obesity on offspring health, and calls on future research to investigate the maternal and newborn health in underrepresented populations, such as NHPI.

The authors have declared no competing interest.

This study was supported by the National Institutes of Health grants R01 LM012373 and LM012907 from the National Library of Medicine (NLM), and grant R01 HD084633 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), awarded to L.X. Garmire. This research was supported in part by training funding provided by the NIH grant T32 GM141746 and Advanced Proteogenomics of Cancer (T32 CA140044).

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Western IRB of the University of Hawaii gave ethical approval for this work (WIRB Protocol #20151223). All participants involved in this study provided written informed consent before the collection of cord blood samples.

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