Brain-derived neurotrophic factor (BDNF) in neonatal blood: associations with respiratory disease in extremely preterm infants.
prospective_cohort · Level II
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- Also identified by DOI 10.1038/s41390-026-05321-9.
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Abstract
Neurotrophins, including brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NT-4), have been associated with the development of bronchopulmonary dysplasia (BPD) in preterm infants. To evaluate relationships between early postnatal BDNF and NT-4 levels and adverse pulmonary outcomes among preterm infants. We analyzed data from the Extremely Low Gestational Age Newborn (ELGAN) cohort. Serum BDNF and NT-4 were measured at birth and postnatal days 7, 14, 21, and 28. Pulmonary outcomes included BPD and early respiratory patterns predictive of BPD, specifically, pulmonary deterioration (PD) and early and persistent pulmonary dysfunction (EPPD). Associations were evaluated using regression models adjusted for perinatal confounders. NT-4 levels were not associated with BPD risk. Persistently high BDNF trajectories were associated with reduced risk, while persistently low BDNF was associated with increased risk of BPD, PD, and EPPD (BPD: OR 2.75; 95% CI 1.83-4.15; PD: OR 3.13; 95% CI 1.60-6.14; and EPPD: OR 7.94; 95% CI 3.70-17.04). Infants with persistently low and intermediate BDNF trajectories had higher risk of adverse pulmonary outcomes compared with those with persistently high BDNF levels. Longitudinal BDNF trajectories identify subgroups of preterm infants at differential risk for adverse respiratory outcomes. Persistently high BDNF during the first month of life may be protective and a potential target for preventive strategies. Persistently low brain-derived neurotrophic factor (BDNF) levels during the first postnatal month are associated with increased risk and severity of bronchopulmonary dysplasia (BPD) and early adverse respiratory phenotypes in extremely preterm infants. Longitudinal BDNF trajectories provide greater discrimination of respiratory risk than single time-point measurements. Infants with persistently high BDNF have the lowest risk of pulmonary deterioration, early persistent pulmonary dysfunction, and severe BPD. These findings support BDNF as a potential early biomarker of lung disease progression in preterm infants.