Cord Blood Markers and NBNA Scores Predict Early Neurodevelopment in GDM Infants

Umbilical cord blood levels of neuron-specific enolase (NSE) and brain-derived neurotrophic factor (BDNF), assessed together with Neonatal Behavioral Neurological Assessment (NBNA) scores, may help identify which infants born to mothers with gestational diabetes mellitus (GDM) face short-term neurodevelopmental difficulties, according to a prospective cohort study conducted at Suzhou High-tech Zone People’s Hospital in China.

The study enrolled 140 term neonates born to mothers with GDM between January 2023 and December 2024. Researchers measured NSE and BDNF in cord blood at birth and performed the NBNA on postnatal day 3. At six months of age, neurodevelopment was evaluated using the Gesell Developmental Scales, and infants were stratified into an abnormal group, defined by a developmental quotient (DQ) below 85, and a normal group with a DQ of 85 or above.

Twenty-seven infants, or 19.3 percent of the cohort, were classified as abnormal, while 113 infants, or 80.7 percent, were classified as normal. The abnormal group showed significantly higher cord blood NSE levels and significantly lower BDNF levels than the normal group, with differences reaching statistical significance at P < 0.01. NBNA scores were also significantly lower in the abnormal group, and the proportion of infants with NBNA abnormality was higher in that group.

Multivariate analysis identified elevated NSE as an independent risk factor for abnormal neurodevelopment at six months. Higher BDNF levels and higher NBNA scores, by contrast, emerged as protective factors, with P values below 0.05 and below 0.01 respectively.

The predictive performance of the combined model was assessed using receiver operating characteristic (ROC) curves. When NSE, BDNF, and NBNA scores were considered together, the model yielded an area under the curve (AUC) of 0.873, with a 95 percent confidence interval of 0.786 to 0.961. The combined assessment achieved a sensitivity of 77.78 percent and a specificity of 89.38 percent, indicating favorable discrimination between infants who later showed abnormal development and those who did not.

The study’s findings align these biochemical and behavioral markers with later developmental outcomes measured by the Gesell scales.

The authors conclude that elevated cord blood NSE, reduced BDNF levels, and lower NBNA scores are significantly associated with adverse neurodevelopmental outcomes at six months in offspring of mothers with GDM, and that the combined assessment demonstrates favorable predictive performance for early identification of neurodevelopmental risk.

Important limitations remain. The study followed infants only to six months of age, a short-term window, and the authors note that longer follow-up is needed to determine whether the combined assessment can predict definitive long-term neurodevelopmental disorders. The cohort consisted of term neonates from a single hospital, and the results reflect associations and predictive performance within this specific population rather than established causal effects or clinical recommendations.

Subject of Research: Predicting short-term neurodevelopment in infants of mothers with gestational diabetes using cord blood NSE, BDNF, and NBNA scores

Article Title: Predictive value of umbilical cord blood NSE and BDNF levels combined with NBNA scores for short-term neurodevelopment in offspring of mothers with gestational diabetes mellitus

Article References: Gao, L.-L., Wang, Y.-M., Zhou, Q., Qu, Q.-F., & Yin, Q.-G. (2026). Predictive value of umbilical cord blood NSE and BDNF levels combined with NBNA scores for short-term neurodevelopment in offspring of mothers with gestational diabetes mellitus. BMC Pediatrics. https://doi.org/10.1186/s12887-026-07864-6

Image Credits: AI Generated

DOI: 10.1186/s12887-026-07864-6

Keywords: gestational diabetes mellitus, umbilical cord blood, neuron-specific enolase, brain-derived neurotrophic factor, NBNA, neurodevelopment, Gesell Developmental Scales, ROC analysis, prospective cohort, neonates, Predictive, value