Article

Maternal Metabolome Research Identifies Possible Lifetime Health Risks

But new findings offer potential for early clinical intervention

3-D image of metabolites

Studies of the maternal metabolome during pregnancy have demonstrated that biomarkers identified as indicators of lifetime risks for obesity, diabetes, cardiovascular and kidney disease, are associated with newborn adiposity and cord C-peptide, according to findings published recently in Diabetologia.

Duke molecular researcher James R. Bain, PhD, an author of the study, says the results should encourage early clinical prevention efforts before metabolic disease or related comorbidities develop in children.

The metabolomics substudy of the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study, a large international investigation, examined small-molecule metabolites in fasting and one-hour serum samples from pregnant women. Both the large sample size (1,600 mothers) and international scope of the project were unusual, Bain says. Maternal blood samples were obtained between 24 and 32 weeks’ gestation, and cord-blood samples were secured following birth.

Key findings of the HAPO Metabolomics Study:

  • At one-hour post-glucose load, several maternal amino acids and lipid metabolites were associated with newborn birthweight, cord C-peptide, and/or sum of skinfolds. Some of these associations were independent of maternal body mass index or glucose level.
  • At one hour, maternal branched-chain amino acids were associated with cord C-peptide levels, a measure of fetal insulinemia.
It’s clear from previous studies, as a broad generality, that if a child is born somewhat larger than average, such as many of those we studied in this analysis, their lifelong risk of diabetes, obesity, cardiovascular disease, or kidney disease is higher than the risk for those babies who have normal birthweights.
James R. Bain, PhD

Bain says the HAPO data offer a valuable resource for the study of the long-term health effects of subtle metabolic changes in a mother’s physiology during pregnancy.

“It’s clear from previous studies, as a broad generality, that if a child is born somewhat larger than average, such as many of those we studied in this analysis, their lifelong risk of diabetes, obesity, cardiovascular disease, or kidney disease is higher than the risk for those babies who have normal birthweights,” Bain says.

Metabolic researchers have long suspected that maternal metabolites during pregnancy might affect in-utero development of fetal metabolic tissues. But new approaches to predict and possibly prevent metabolic disease are suggested by the HAPO findings.

Bain performs research within the Metabolomics Lab in the Duke Molecular Physiology Institute, and he serves on the faculty of the Division of Endocrinology, Metabolism, and Nutrition, in Duke’s Department of Medicine. The lab has launched additional studies to assess the long-term impact of subtle metabolic changes in a mother’s physiology during pregnancy. Bain is performing this research in collaboration with investigators from the Northwestern University Feinberg School of Medicine, where the HAPO study is based.