Prepregnant Obesity of Mothers in a Multiethnic Cohort Is Associated with Cord Blood Metabolomic Changes in Offspring

Maternal obesity
has become a growing global health concern that
may predispose the offspring to medical conditions later in life.
However, the metabolic link between maternal prepregnant obesity and
healthy offspring has not yet been fully elucidated. In this study,
we conducted a case-control study using a coupled untargeted and targeted
metabolomic approach from the newborn cord blood metabolomes associated
with a matched maternal prepregnant obesity cohort of 28 cases and
29 controls. The subjects were recruited from multiethnic populations
in Hawaii, including rarely reported Native Hawaiian and other Pacific
Islanders (NHPI). We found that maternal obesity was the most important
factor contributing to differences in cord blood metabolomics. Using
an elastic net regularization-based logistic regression model, we
identified 29 metabolites as potential early-life biomarkers manifesting
intrauterine effect of maternal obesity, with accuracy as high as
0.947 after adjusting for clinical confounding (maternal and paternal
age, ethnicity, parity, and gravidity). We validated the model results
in a subsequent set of samples (N = 30) with an accuracy
of 0.822. Among the metabolites, six metabolites (galactonic acid,
butenylcarnitine, 2-hydroxy-3-methylbutyric acid, phosphatidylcholine
diacyl C40:3, 1,5-anhydrosorbitol, and phosphatidylcholine acyl-alkyl
40:3) were individually and significantly different between the maternal
obese and normal-weight groups. Interestingly, hydroxy-3-methylbutyric
acid showed significantly higher levels in cord blood from the NHPI
group compared to that from Asian and Caucasian groups. In summary,
significant associations were observed between maternal prepregnant
obesity and offspring metabolomic alternation at birth, revealing
the intergenerational impact of maternal obesity.