Identifying a Shared Metabolomic Signature in Mother–Newborn Dyads With and Without Gestational Diabetes: Implications for Early Metabolic Programming

Pregnancy is a critical window for metabolic programming, during which adverse intrauterine exposures may influence long-term health. GDM alters the intrauterine environment, but its role in early metabolic programming remains poorly understood. Thus, the objective of this study was to identify the shared metabolomic signature in mother–newborn dyads and to assess whether GDM modifies this signature. For this purpose, we conducted a cross-sectional study including mother–newborn dyads recruited at the General Hospital of Mexico. Blood samples were collected from dyads. Amino acids and acylcarnitines were quantified by tandem mass spectrometry. Sparse partial least squares (sPLS) analysis was used to identify shared metabolomic signatures within mother–newborn dyads. Linear mixed-effects models evaluated the modifying effect of GDM on shared metabolites. A total of 112 mother–newborn dyads (68 without GDM and 44 with GDM) were included. Two shared metabolomic signatures were identified. The first, characterized by arginine, methionine, acetylcarnitine, and free carnitine, showed a strong maternal–newborn correlation. Although this core signature was preserved in both groups, valine and alanine contributed exclusively to the GDM-exposed dyads. In conclusion, a shared metabolomic signature related to fetal development and energy metabolism was conserved regardless of GDM status, although GDM partially modified this signature. These findings provide insights into metabolic processes potentially involved in early metabolic programming.