Maternal Obesity Reshapes Umbilical Cord Blood Adipokine Profile in Term Newborns

Babies born to mothers with obesity carry a measurably different cocktail of metabolic signaling proteins in their umbilical cord blood, according to a prospective exploratory cohort study conducted at Balıkesir University Faculty of Medicine Hospital in Türkiye. The research measured three adipokines—leptin, neuregulin-4 (NRG4) and isthmin-1 (ISM1)—in cord blood from 82 term singleton pregnancies delivered by cesarean section between March and May 2026. The findings suggest that the intrauterine environment shaped by maternal obesity leaves a detectable biochemical signature in the newborn, even before any clinical differences emerge.

The study team classified participants into two groups based on first-trimester body mass index: 40 women with obesity, defined as a BMI of 30 kg/m² or higher, and 42 women without obesity, whose BMI was below that threshold. The researchers recorded maternal demographic and biochemical characteristics alongside neonatal clinical outcomes, then quantified leptin, NRG4 and ISM1 concentrations in umbilical cord blood using enzyme-linked immunosorbent assay (ELISA). Their statistical toolkit included between-group comparisons, partial correlation analysis, multivariate analysis of covariance (MANCOVA) and analysis of covariance (ANCOVA), allowing them to test both the overall effect of maternal obesity on the adipokine profile and the independent contribution of each individual protein.

Two glucose findings stood out before any adipokine analysis began. Maternal glucose concentrations were significantly higher in the obese group, while neonatal glucose concentrations were significantly lower, with reported p-values of 0.009 and less than 0.001 respectively. Because the study is exploratory and observational, this opposing pattern in mother and newborn describes an association rather than a demonstrated mechanism.

The adipokine results formed the core of the investigation. Compared with the non-obese group, cord blood from newborns of mothers with obesity contained significantly increased concentrations of leptin and ISM1, while NRG4 concentrations were significantly decreased, with all three comparisons reaching statistical significance at p less than 0.05. Leptin is the best characterized of the three proteins, whereas NRG4 and ISM1 are less extensively studied adipokines whose contribution to the fetal metabolic profile had remained incompletely understood.

When the researchers applied MANCOVA, the analysis demonstrated a significant overall effect of maternal obesity on the cord blood adipokine profile, with leptin contributing most strongly to that association. After adjustment, leptin remained independently associated with maternal obesity in the ANCOVA model, with a p-value below 0.001 and an effect size of η² = 0.28—a substantial proportion of variance explained for a single biomarker. ISM1 and NRG4, however, lost their independent significance once the model accounted for the other variables, suggesting that their apparent group differences were intertwined with the broader adipokine shift rather than standing alone as separate signals.

Partial correlation analysis added another layer to the picture, revealing positive associations among the investigated adipokines. The strongest correlation was observed between ISM1 and NRG4, with a correlation coefficient of r = 0.88 and a p-value below 0.001. Such tight coupling between two emerging adipokines, one rising and one falling on average in the obese group, points to coordinated regulation of these proteins in the fetal compartment, although the cross-sectional cord blood measurements cannot establish the direction or mechanism of that relationship.

Notably, the biochemical differences were not mirrored in immediate clinical outcomes. The study found no significant differences between the two groups in neonatal complications, Apgar scores, umbilical cord blood pH, lactate concentrations, bilirubin concentrations, or admission to the neonatal intensive care unit. In other words, the altered adipokine profile existed alongside apparently normal early neonatal wellbeing in this cohort of term newborns delivered by cesarean section.

The authors interpret these changes as potential early metabolic adaptations to an obesogenic intrauterine environment rather than markers of immediate harm. The concept of fetal metabolic programming holds that conditions in the womb can shape long-term metabolic risk, and cord blood adipokines may serve as accessible biomarkers reflecting that process. Because leptin has been extensively investigated in pregnancies complicated by maternal obesity, the study’s contribution lies partly in extending the profile to NRG4 and ISM1, proteins whose roles in fetal development are only beginning to be mapped.

The researchers caution that their findings require confirmation in larger prospective longitudinal studies before any clinical application. The cohort was modest in size, restricted to term singleton births by cesarean section at a single hospital, and the exploratory design cannot establish causality or predict later childhood outcomes. Still, the study provides a detailed snapshot of how maternal obesity is associated with a coordinated shift in fetal adipokine biology—one marked by a robust leptin increase, a decline in NRG4, and tightly correlated ISM1 and NRG4 concentrations—captured at the very first moment of extrauterine life.

Subject of Research: Umbilical cord blood adipokine changes associated with maternal obesity

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

Article References: Efe Camili, F., Aycan, O. K., Yilmaz, M. A., Afsar, S., Guney, G., & Taskin, M. İ. (2026). Altered umbilical cord adipokine profile associated with maternal obesity: an exploratory cohort study. Frontiers in Endocrinology, 17, Article 1936173. https://doi.org/10.3389/fendo.2026.1936173

Image Credits: AI Generated

DOI: 10.3389/fendo.2026.1936173

Keywords: maternal obesity, umbilical cord blood, adipokines, leptin, neuregulin-4, isthmin-1, fetal metabolic programming, neonatal outcomes, prospective cohort study, ELISA, glucose, Altered