Altered umbilical cord adipokine profile associated with maternal obesity: an exploratory cohort study

Background Maternal obesity is associated with adverse pregnancy outcomes and may influence fetal metabolic programming through alterations in the intrauterine environment. While leptin has been extensively investigated in pregnancies complicated by maternal obesity, the contribution of emerging adipokines, including neuregulin-4 (NRG4) and isthmin-1 (ISM1), to the fetal adipokine profile remains incompletely understood. This study aimed to characterize alterations in the umbilical cord blood adipokine profile associated with maternal obesity and to evaluate their relationship with early neonatal outcomes. Materials and methods This prospective exploratory cohort study was conducted at Balıkesir University Faculty of Medicine Hospital, Balıkesir, Türkiye, and included 82 term singleton pregnancies delivered by cesarean section between March and May 2026. Participants were classified as obese (first-trimester BMI ≥30 kg/m², n=40) or non-obese (BMI <30 kg/m², n=42). Maternal demographic and biochemical characteristics, together with neonatal clinical outcomes, were recorded. Umbilical cord blood leptin, NRG4, and ISM1 concentrations were measured using enzyme-linked immunosorbent assay (ELISA). Between-group comparisons, partial correlation analysis, multivariate analysis of covariance (MANCOVA), and analysis of covariance (ANCOVA) were performed. Results Maternal glucose concentrations were significantly higher, whereas neonatal glucose concentrations were significantly lower, in the obese group (p = 0.009 and p < 0.001, respectively). Compared with the non-obese group, cord blood leptin and ISM1 concentrations were significantly increased, while NRG4 concentrations were significantly decreased (all p < 0.05). MANCOVA demonstrated a significant overall effect of maternal obesity on the adipokine profile, with leptin contributing most strongly to this association. Following adjustment, leptin remained independently associated with maternal obesity (ANCOVA: p < 0.001, η² = 0.28), whereas ISM1 and NRG4 were no longer independently significant. Partial correlation analysis demonstrated positive associations among the investigated adipokines, with the strongest correlation observed between ISM1 and NRG4 (r = 0.88, p < 0.001). No significant differences were observed between the groups regarding neonatal complications, Apgar scores, umbilical cord blood pH, lactate, bilirubin concentrations, or neonatal intensive care unit admission. Conclusion Maternal obesity was associated with an altered umbilical cord adipokine profile characterized by a robust increase in leptin together with coordinated alterations in emerging adipokines. Although these biochemical changes were not accompanied by differences in early neonatal outcomes, they may represent early metabolic adaptations to an obesogenic intrauterine environment. These findings support the potential role of cord blood adipokines as biomarkers of fetal metabolic programming and warrant confirmation in larger prospective longitudinal studies.