Bronchopulmonary dysplasia is a chronic lung disease that develops in premature infants, most often those born before 28 weeks of gestation who need breathing support after birth. It remains the most common serious respiratory complication of prematurity, and its effects can extend well beyond the neonatal intensive care unit, shaping lung health and neurodevelopment for years. What makes BPD especially tricky is that the condition has changed over the decades as neonatal medicine has improved, meaning the disease doctors see today looks quite different from what was first described in the late 1960s.
How the Disease Has Changed
When BPD was first described, it was driven largely by the damage that high-pressure ventilators and concentrated oxygen inflicted on premature lungs. That “classic” form involved scarring and fibrosis of lung tissue. Today, thanks to gentler ventilation, surfactant therapy, and antenatal steroids, the pattern has shifted. What clinicians now call “new BPD” is less about overt scarring and more about disrupted lung development: the tiniest air sacs (alveoli) and the blood vessels that supply them simply do not grow and branch the way they should.1PubMed. From classic to new bronchopulmonary dysplasia The lungs end up with fewer, larger alveoli and a thinner network of capillaries, which limits how efficiently they can exchange oxygen and carbon dioxide. That shift matters for parents and clinicians alike, because the strategies aimed at preventing injury to a developing lung are different from those aimed at limiting damage to an already-formed one.
How BPD Is Diagnosed and Graded
Diagnosis historically hinged on whether a premature baby still needed supplemental oxygen at 36 weeks postmenstrual age (that is, 36 weeks from the start of the pregnancy, not from birth). More recent evidence-based criteria focus on the mode of respiratory support at that same time point, regardless of how much extra oxygen the baby is receiving. Under this grading system, an infant on no support has no BPD; one on low-flow nasal cannula has grade 1; higher-flow or noninvasive positive-pressure support means grade 2; and an infant still on a mechanical ventilator is classified as grade 3.2PubMed Central. The Diagnosis of Bronchopulmonary Dysplasia in Very Preterm Infants. An Evidence-based Approach These grades track real-world outcomes well: in the study that proposed them, the rate of death or serious respiratory illness by early childhood rose from about 10% for infants without BPD to 77% for those with grade 3 disease, with a similar gradient for neurodevelopmental problems.3PubMed Central. The Diagnosis of Bronchopulmonary Dysplasia in Very Preterm Infants. An Evidence-based Approach
What Drives the Lung Injury
Several overlapping forces conspire to keep an extremely premature infant’s lungs from developing normally. The two biggest culprits are oxygen exposure and mechanical ventilation, but the story is more layered than that.
Premature infants often need supplemental oxygen to survive, yet high oxygen concentrations are toxic to immature lung tissue. Excess oxygen degrades a signaling protein called HIF-1α, which in turn suppresses vascular endothelial growth factor (VEGF), a molecule the lungs need to build new blood vessels and air sacs.4Journal of Lung, Pulmonary & Respiratory Research. Oxygen injury in neonates: which is worse? hyperoxia, hypoxia, or alternating hyperoxia/hypoxia Animal models confirm that hyperoxia leads to significantly lower VEGF levels compared with controls.5PubMed Central. Hyperoxia-induced lung structure-function relation, vessel rarefaction, and cardiac hypertrophy in an infant rat model Without adequate VEGF, the blood vessel network stalls, and the alveoli that depend on those vessels fail to multiply.
Mechanical ventilation compounds the problem through several mechanisms. Excessive airway pressure can stretch and tear fragile tissue. Large delivered volumes overdistend air sacs. Repeated collapse and re-opening of unstable alveoli generates further inflammation. The premature lung is especially vulnerable to all of these forces, and the injury can worsen the underlying developmental disruption that prematurity already set in motion.6PubMed. Mechanisms of ventilator-induced lung injury in premature infants
Risk Factors Before and After Birth
The biggest single predictor of BPD is how early a baby is born. But prematurity alone does not fully explain who develops the disease and who does not. Several other factors raise or lower the odds.
Chorioamnionitis, an infection of the membranes surrounding the fetus, is a common antenatal risk factor. A large meta-analysis covering more than a hundred studies found that exposure to chorioamnionitis roughly doubled the odds of developing BPD when defined at 28 days of life, and raised the odds by about 30% when defined at 36 weeks postmenstrual age.7PubMed Central. Association of Chorioamnionitis With Bronchopulmonary Dysplasia Among Preterm Infants: A Systematic Review, Meta-analysis, and Metaregression The relationship is partly explained by the fact that babies exposed to chorioamnionitis tend to be born earlier and are more likely to develop respiratory distress, both of which independently raise BPD risk.8PubMed Central. Association of Chorioamnionitis With Bronchopulmonary Dysplasia Among Preterm Infants: A Systematic Review, Meta-analysis, and Metaregression
Fetal growth restriction is another key antenatal factor. Preterm infants who were small for their gestational age have a higher incidence of BPD, and research suggests this is tied to impaired blood vessel formation in the lungs. One study found that growth-restricted preterm infants had thicker, stiffer pulmonary arteries, consistent with abnormal vascular development that limits later lung growth.9PubMed Central. Preterm growth restriction and bronchopulmonary dysplasia: the vascular hypothesis and related physiology
The Role of Genetics
Not every very premature baby with similar clinical exposures develops BPD. Twin studies estimate that the heritability of moderate-to-severe BPD falls between roughly 53% and 79%, which is remarkably high for a disease so closely tied to environmental exposures like oxygen and ventilation.10PubMed Central. A genome-wide association study (GWAS) for bronchopulmonary dysplasia Genome-wide association studies have begun to identify specific gene variants that raise susceptibility. A Finnish study, for instance, flagged a variant near the CRP gene — the gene encoding C-reactive protein, a marker of inflammation — as a risk factor for BPD, independent of other known predictors.11Scientific Reports. Genome-wide association study of bronchopulmonary dysplasia: a potential role for variants near the CRP gene Elevated CRP levels during the first week of life also independently predicted the disease in that cohort.
Genetic variation related to lung development, drug metabolism, and immune response also appears to contribute to racial and ethnic differences in respiratory outcomes among premature infants.12PubMed Central. Ancestry and genetic associations with bronchopulmonary dysplasia in preterm infants Researchers are still far from being able to predict individual risk with a genetic test, but the heritability data make clear that biology, not just treatment exposure, plays a substantial role.
Preventing and Treating BPD
Prevention starts before birth. Antenatal corticosteroids given to mothers at risk of preterm delivery accelerate fetal lung maturation, boost surfactant production, and reduce the incidence of respiratory distress syndrome, which in turn lowers the downstream risk of BPD.13PubMed Central. Antenatal corticosteroids to prevent neonatal respiratory distress syndrome This is one of the most well-established interventions in neonatal medicine and is standard of care worldwide.
After birth, respiratory management focuses on minimizing additional lung damage. That means using the gentlest effective mode of breathing support, targeting lower oxygen levels than were once common, and weaning ventilation as quickly as is safe.14PubMed Central. Respiratory support strategies in the prevention and treatment of bronchopulmonary dysplasia Noninvasive approaches like continuous positive airway pressure (CPAP) are preferred over mechanical ventilation whenever possible, because every additional day on a ventilator contributes to the cycle of injury and inflammation.
Caffeine has become a staple of NICU care for very preterm infants. It stimulates breathing and helps babies wean off ventilatory support sooner. For infants born after 28 weeks of gestation, starting caffeine early rather than waiting was associated with about 1.3 fewer days on mechanical ventilation and roughly a 37% reduction in the odds of moderate-to-severe BPD.15BMJ Open. Impact of early caffeine administration on respiratory outcomes in very preterm infants initially receiving invasive mechanical ventilation
Postnatal corticosteroids are a more contentious tool. A Cochrane overview found that early systemic dexamethasone reduces the combined risk of death or BPD at 36 weeks — with roughly one in 13 treated infants benefiting who otherwise would not have.16Cochrane Database of Systematic Reviews. Postnatal corticosteroids in preterm infants at risk of bronchopulmonary dysplasia: an overview of systematic reviews However, the benefits come with serious potential harms including cerebral palsy, neurosensory disability, and gastrointestinal perforation.17Cochrane Database of Systematic Reviews. Postnatal corticosteroids in preterm infants at risk of bronchopulmonary dysplasia: an overview of systematic reviews Other reported side effects of postnatal steroids include high blood sugar, high blood pressure, infection, cardiac changes, and poor head growth.18PubMed Central. Impact of Postnatal Corticosteroid (PNS) Use on Neurodevelopment at 18-22 Months Adjusted Age Because of these risks, postnatal steroids are generally reserved for infants on high ventilator settings who cannot be weaned, and the decision involves careful weighing of the individual baby’s situation.
Nutrition and Human Milk
Aggressive nutritional support is central to BPD management, though the connection is often underappreciated by families. Premature lungs need energy and building blocks to grow, and poor nutrition slows recovery. Human milk appears to have a specific protective role beyond basic calories: it contains a range of antioxidant compounds, including enzymes like superoxide dismutase and glutathione peroxidase, as well as vitamins, melatonin, and short-chain fatty acids. These antioxidants may help counteract the oxidative damage that drives BPD by reducing cell death, dampening inflammation, and supporting the growth of new blood vessels in the lungs.19PubMed Central. Effects of Antioxidants in Human Milk on Bronchopulmonary Dysplasia Prevention and Treatment: A Review This is one of the reasons NICUs strongly encourage breast milk feeding for extremely preterm infants, even when the volumes are tiny at first.
Pulmonary Hypertension as a Complication
One of the most dangerous complications of BPD is pulmonary hypertension — abnormally high blood pressure in the arteries that connect the heart to the lungs. About a quarter of infants with moderate-to-severe BPD develop it, and the consequences are severe: nearly half of BPD infants diagnosed with pulmonary hypertension die within two years of that diagnosis.20PubMed Central. Pulmonary hypertension in bronchopulmonary dysplasia The underdeveloped blood vessel network in BPD lungs is the root of the problem — fewer, stiffer vessels mean the right side of the heart has to work harder to push blood through, eventually straining and enlarging it. Screening for pulmonary hypertension with echocardiography is now a routine part of BPD care, because catching it early allows treatment with medications that relax pulmonary blood vessels.
Long-Term Lung Health
BPD is not just a neonatal problem. Adults who survived BPD as infants have measurably worse lung function than both preterm-born adults without BPD and adults born at full term.21PubMed. Impaired lung function and health status in adult survivors of bronchopulmonary dysplasia The impairment shows up as reduced airflow, particularly in the smaller airways, and it translates into lower quality-of-life scores on respiratory questionnaires.
The underlying reason is what researchers describe as “inharmonious growth.” After birth, alveolar structures grow more rapidly than the airways, creating a mismatch that leads to airflow obstruction and air trapping. Both extremely premature infants with and without a formal BPD diagnosis can show these features, but those who had BPD perform worse on lung function tests throughout childhood and into adulthood.22Pulmonary Pharmacology & Therapeutics. Respiratory outcomes of preterm infants: From discharge to adult life The concern is that this trajectory places BPD survivors at increased risk for early-onset chronic obstructive pulmonary disease later in life — a disease normally associated with decades of smoking, but potentially reachable much sooner when lung development was compromised from the start.
Neurodevelopmental Impact
The brain and the lungs of a premature infant are developing on parallel timelines, and damage to one often accompanies trouble in the other. Infants who still require mechanical ventilation at 36 weeks postmenstrual age face significantly increased odds of cerebral palsy, developmental delay at two years, and poor academic achievement and lower IQ scores in adolescence.23PubMed. Neurodevelopmental outcomes of infants with bronchopulmonary dysplasia Severity matters enormously: infants with severe BPD at 40 weeks postmenstrual age had mental development scores roughly 26 points lower and motor scores about 20 points lower than infants without BPD.24PubMed Central. Bronchopulmonary dysplasia—impact of severity and timing of diagnosis on neurodevelopment of preterm infants
Chronic hypoxia, inflammation, and the cumulative stress of prolonged intensive care all contribute to these neurodevelopmental gaps. This is why BPD care teams increasingly include developmental specialists, and why long-term follow-up programs track cognitive and motor milestones well into school age.
When Severe BPD Requires a Tracheostomy
A small but growing number of infants with severe BPD cannot be weaned from a ventilator despite months of effort. For these babies, tracheostomy — a surgically placed opening in the windpipe — has become the most common indication for the procedure in infants under one year of age.25PubMed Central. Tracheostomy in infants with severe bronchopulmonary dysplasia: A review While the idea of a tracheostomy understandably frightens families, a growing body of evidence suggests it can actually benefit growth and development in severely affected infants by providing a more stable airway and allowing the baby to leave the hospital on a portable ventilator.26PubMed. Long-term ventilation for children with chronic lung disease of infancy Clinical teams generally consider tracheostomy when airway softening is present, ventilator settings remain very high, oxygen requirements are steep, and the infant is approaching or past 44 weeks postmenstrual age without progress toward weaning.27Journal of Perinatology. Qualitative indications for tracheostomy and chronic mechanical ventilation in patients with severe bronchopulmonary dysplasia
Life After the NICU
Discharge from the hospital does not mean BPD is resolved. Many infants go home on supplemental oxygen, and those who do have higher rates of readmission for respiratory illness and are more likely to develop wheezing disorders in the first year.28PubMed Central. Home oxygen use and 1-year outcome among preterm infants with bronchopulmonary dysplasia discharged from a Chinese regional NICU Respiratory syncytial virus (RSV) and other common childhood infections can hit BPD infants especially hard, which is why preventive measures like palivizumab (an RSV antibody) and strict hand hygiene are emphasized at discharge.
Where a family lives matters, too. Infants from neighborhoods with higher deprivation had significantly more emergency department visits, and Medicaid insurance was independently associated with roughly triple the odds of ED visits compared with private insurance.29PubMed. Social Determinants of Health and Healthcare Utilization in Infants With Bronchopulmonary Dysplasia Environmental exposures add another layer of risk. One study found that diesel particulate matter and airborne cancer-related toxics roughly doubled the odds of a medically attended respiratory illness in BPD infants, and that these pollutants accounted for about 39% of the disparity in respiratory illness between Black and white infants with BPD.30PubMed Central. Environmental Determinants of Post-Discharge Acute Respiratory Illness among Preterm Infants with Bronchopulmonary Dysplasia Neighborhood social vulnerability also played a role, mediating about 31% of the Black-white disparity in ED visits.31Journal of Perinatology. Associations of neighborhood social vulnerability with emergency department visits and readmissions among infants with bronchopulmonary dysplasia These findings make a strong case that improving BPD outcomes requires attention not just to what happens in the hospital, but to the air quality and socioeconomic conditions that families face after discharge.
The Airway Microbiome
An emerging area of research examines how the microbial communities in a premature infant’s lungs and gut might influence whether BPD develops. Recent work has found that infants who went on to develop BPD had distinctly different microbial communities in both the airway and the gut compared with those who did not. In particular, skin-associated bacteria — especially Staphylococcus epidermidis — were enriched in the lungs and guts of infants who developed BPD and was the most prominent species shared between the two sites.32PubMed Central. Increased S. epidermidis in the airway-gut microbiome of infants with bronchopulmonary dysplasia The hypothesis is that disrupted early microbial colonization, possibly influenced by antibiotics, prolonged intubation, and the sterile NICU environment, triggers inflammatory pathways that worsen lung injury. Whether manipulating the microbiome through probiotics or other means could prevent BPD is still highly speculative, but the consistently observed microbial differences between affected and unaffected infants suggest this is a thread worth pulling.
Stem Cell Therapy on the Horizon
Perhaps the most anticipated experimental approach involves mesenchymal stem cells (MSCs) and the tiny vesicles they release. In animal models, treatment with MSCs or their extracellular vesicles has reduced lung inflammation, improved the architecture of developing air sacs, lessened fibrosis, and improved survival rates.33PubMed Central. Stem-Cell Therapy for Bronchopulmonary Dysplasia (BPD) in Newborns Early-phase human trials are underway or recently completed in several countries, and the results so far have been encouraging enough to justify larger studies, though no stem-cell product is approved for BPD treatment yet. The appeal of this approach is that it addresses the root problem: it potentially restores the disrupted growth signals that the premature lung needs, rather than simply managing the downstream symptoms. If the clinical data hold up, it could represent the biggest shift in BPD care since surfactant therapy was introduced decades ago.