A molecule best known for helping neurons survive and form connections may also provide an early biological signal of respiratory disease in the most vulnerable newborns. In a study published in Pediatric Research, researchers examined brain-derived neurotrophic factor, or BDNF, in neonatal blood and explored its relationship with respiratory outcomes among extremely preterm infants. The findings add to growing evidence that the biology of the developing nervous system is closely intertwined with the immature lung, potentially opening a new path toward identifying infants at greatest risk of bronchopulmonary dysplasia, a chronic respiratory condition that can follow premature birth.
BDNF belongs to the neurotrophin family, a group of signaling proteins that regulate the growth, survival and specialization of nerve cells. It is produced in several tissues, including the brain, peripheral nerves, immune cells and possibly the developing lung. BDNF primarily acts by binding to tropomyosin receptor kinase B, known as TrkB, a receptor that activates intracellular pathways involved in cell survival, differentiation and tissue repair. Another neurotrophin, neurotrophin-4, can also signal through TrkB. Although these proteins are traditionally discussed in the context of brain development, researchers have increasingly investigated their role in pulmonary development and injury.
Extremely preterm infants are born during a period when the lungs are still undergoing major structural and functional changes. The distal airways and alveoli are not yet fully developed, and the systems responsible for producing pulmonary surfactant—the mixture that prevents the tiny air sacs from collapsing—may be immature. After birth, these infants may require oxygen therapy and mechanical ventilation to maintain adequate gas exchange. While such treatments can be lifesaving, prolonged exposure to elevated oxygen concentrations, pressure and inflammation can disrupt normal lung development and contribute to BPD.
BPD is not caused by a single process. It reflects the interaction of developmental immaturity, prenatal and postnatal inflammation, infection, oxygen exposure, mechanical stress and genetic susceptibility. The condition is commonly identified through a combination of respiratory support requirements and clinical assessment at a defined postmenstrual age. Infants who develop BPD may face prolonged hospitalization and an increased risk of wheezing, recurrent respiratory infections, impaired exercise tolerance and abnormal lung function later in childhood. Because the disease evolves over time, an early biomarker could help clinicians distinguish infants whose lungs are likely to recover from those who may need more intensive monitoring.
The study by Stephenson, Yi, Gower and colleagues focused on BDNF concentrations measured in neonatal blood. Blood-based biomarkers are attractive in neonatal medicine because samples can be obtained alongside routine clinical testing, although the volume available from extremely small infants is limited. Measuring BDNF in this setting is technically challenging: concentrations may be influenced by the type of blood sample, platelet activation, timing, storage conditions and the infant’s changing developmental state. For that reason, interpreting a BDNF value requires careful attention to how and when the sample was collected, as well as the clinical circumstances surrounding the infant.
The researchers reported associations between neonatal BDNF levels and respiratory disease among extremely preterm infants. The central significance of this observation is not that BDNF has been proven to cause or prevent BPD, but that it may reflect biological processes linked to the infant’s respiratory trajectory. Altered BDNF could indicate injury, inflammation, impaired tissue maturation or a compensatory repair response. It may also mirror broader communication between the nervous, immune and respiratory systems. These possibilities remain hypotheses, and the direction of the relationship is crucial: a higher or lower concentration could represent either risk or an attempt by the body to restore damaged tissue, depending on the timing and clinical context.
The connection between neurotrophins and the lung is biologically plausible. The developing respiratory system contains nerves and signaling networks that influence airway tone, vascular growth and epithelial behavior. BDNF-TrkB signaling may affect the maturation of airway and alveolar cells, the formation of pulmonary blood vessels and the response to inflammatory stress. At the same time, lung injury can alter neural signaling and the release of growth factors. In a premature infant, these pathways may be especially sensitive because development continues outside the protective environment of the womb, while the lungs are exposed to oxygen, pressure changes and inflammatory stimuli earlier than nature intended.
A major challenge for future research will be determining whether BDNF improves prediction beyond established clinical factors. Gestational age, birth weight, sex, antenatal steroid exposure, infection, respiratory support and oxygen requirement already provide important information about BPD risk. A useful biomarker would need to add measurable accuracy to these factors, work reliably across hospitals and remain interpretable despite normal developmental changes. Researchers will also need to test whether repeated measurements are more informative than a single blood sample and whether BDNF patterns differ between BPD subtypes or between infants exposed to different forms of respiratory support.
The findings nevertheless point toward a broader view of neonatal respiratory disease—one in which the lung cannot be studied in isolation from the nervous and immune systems. If validated in larger, prospective cohorts, BDNF could become part of a biomarker panel designed to identify biological risk before severe respiratory disease is fully established. Such a tool would not replace careful clinical care, but it could support earlier surveillance, more individualized decisions about respiratory support and better selection of infants for future trials of protective therapies. For now, the study offers an intriguing signal from the newborn bloodstream: a protein associated with neural development may also help reveal how the premature lung is coping with life outside the womb.
Subject of Research: The association between neonatal blood BDNF levels and respiratory disease, including bronchopulmonary dysplasia, in extremely preterm infants.
Article Title: Brain-derived neurotrophic factor (BDNF) in neonatal blood: associations with respiratory disease in extremely preterm infants
Article References: Stephenson, N., Yi, J.X., Gower, W.A. et al. Brain-derived neurotrophic factor (BDNF) in neonatal blood: associations with respiratory disease in extremely preterm infants. Pediatr Res (2026). https://doi.org/10.1038/s41390-026-05321-9
Image Credits: AI Generated
DOI: 10.1038/s41390-026-05321-9
Keywords: BDNF, neurotrophins, bronchopulmonary dysplasia, extremely preterm infants, neonatal blood biomarkers, respiratory disease, premature lung development, neonatal medicine
Tags: BDNF and lung tissue repairbiological signals for respiratory diseasebronchopulmonary dysplasia biomarkersearly predictors of respiratory outcomesimmature lung and nervous system developmentneonatal BDNF levelsneonatal neurotrophic factorsneurobiology of preterm infant lung injuryneuroimmune interactions in preterm babiesneurotrophin role in lung developmentpreterm birth and respiratory healthrespiratory disease in preterm infants
