B60-31 Brain-Derived Neurotrophic Factor (BDNF) in Neonatal Blood: Associations With Respiratory Disease in Extremely Preterm Infants

Background

Bronchopulmonary dysplasia (BPD) remains a major morbidity among extremely preterm infants. Neurotrophins, including brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NT-4), are involved in lung development and injury response, but their longitudinal relationships with early respiratory disease phenotypes and BPD severity are not well defined. Objective: To evaluate associations between early postnatal BDNF and NT-4 levels, longitudinal BDNF trajectories, and adverse respiratory outcomes among extremely preterm infants.

Methods

We conducted secondary analyses of the Extremely Low Gestational Age Newborn (ELGAN) Study, a multicenter cohort of infants born <28 weeks’ gestation. Serum BDNF and NT-4 concentrations were measured from dried blood spots collected at birth and postnatal days 7, 14, 21, and 28. Primary outcomes included BPD at 36 weeks postmenstrual age (PMA). Secondary outcomes included early respiratory phenotypes predictive of BPD: pulmonary deterioration (PD) and early persistent pulmonary dysfunction (EPPD). Neurotrophin concentrations were categorized into gestational-age- and postnatal-age-specific quartiles. Logistic regression models were used to assess associations with outcomes, adjusting for gestational age, sex, antenatal corticosteroid exposure, and multiple gestation. In a subset with complete longitudinal data (n = 618), latent trajectory modeling was used to identify distinct BDNF patterns across the first postnatal month.

Results

Among 1,149 infants included in primary analyses, NT-4 levels were not associated with BPD or early respiratory outcomes. In contrast, higher BDNF levels during the first two postnatal weeks were associated with reduced risk of BPD. Infants in the highest BDNF quartile during the first postnatal week had significantly lower odds of BPD compared with those in the lowest quartile (OR 0.45; 95% CI 0.32-0.64). Trajectory modeling identified four distinct BDNF patterns: persistently low, low-then-increasing, high-then-decreasing, and persistently high. Infants with persistently low BDNF had the highest risk of BPD, PD, and EPPD, while those with persistently high BDNF had the lowest risk (PD: OR 0.24; 95% CI 0.11-0.52; EPPD: OR 0.21; 95% CI 0.10-0.45). Non-persistent trajectories were also associated with increased risk compared with persistently high BDNF. Additionally, low BDNF trajectories were associated with greater BPD severity.

Conclusions

Longitudinal BDNF trajectories during the first postnatal month identify subgroups of extremely preterm infants at differential risk for early respiratory dysfunction, BPD, and BPD severity. Persistently high BDNF may reflect protective developmental or reparative processes and represents a potential early biomarker of lung disease progression in this high-risk population.

This abstract is funded by: None