Bronchopulmonary dysplasia (BPD) is a chronic lung disease of premature infants, characterized by disrupted lung development and/or lung injury. It is the most common complication of prematurity. Acute injury to the premature, developing lung, often as a result of necessary neonatal care, may progress to chronic lung injury; this process is influenced by prenatal and perinatal factors, with abnormal repair and remodeling occurring as the lung develops and matures over months to years. The strongest risk factors for BPD are prematurity and low birth weight. It is also more common in infants who require prolonged treatment with supplemental oxygen or mechanical ventilation for respiratory distress syndrome.
The definition of BPD has evolved over time, reflecting changes in the population at risk, such as more survivors at earlier gestational ages and improvements in management including surfactant, antenatal corticosteroids, and less aggressive mechanical ventilation. Clinically, BPD is defined by a persistent need for supplemental oxygen or respiratory support, assessed at 28 days of life or 36 weeks' postmenstrual age, in a preterm infant with radiographic (X-ray) evidence of lung disease. The condition is commonly graded as mild, moderate, or severe (grades 1–3) according to the level of respiratory support required. BPD is associated with significant morbidity and mortality among premature infants. Complications may also extend beyond infancy, particularly in severe BPD, and may include pulmonary hypertension, obstructive lung disease, and poorer neurodevelopmental outcomes.
Discovery In 1967, radiologist William Northway and pathologists Robert Rosan and David Porter first coined the term "bronchopulmonary dysplasia" to describe a "chronic form of injury to the lungs caused by barotrauma and oxygen injury in preterm infants requiring mechanical ventilation". The disease was first observed three years earlier among premature infants treated with high-concentration oxygen and intermittent positive pressure ventilation, noted by neonatologist Philip Sunshine at Stanford University Medical Center.
Presentation Bronchopulmonary dysplasia is characterized by a persistent need for supplemental oxygen or respiratory support with clinical and radiographic evidence of parenchymal lung disease. Physical findings commonly include tachypnea and increased work of breathing; coarse breath sounds and wheezing may also be present. Blood gas testing may show chronic carbon dioxide retention. Feeding problems are common in infants with BPD, and may include difficulty swallowing and an increased risk of aspiration.
Chest radiographic (X-ray) findings in BPD vary with disease severity and may change over time. In milder disease, radiographs may show diffuse haziness, coarse interstitial markings, and areas of atelectasis. More severe disease may be associated with hyperexpanded lungs, flattened diaphragms, and heterogeneous areas of atelectasis and scarring. Over time, radiographs may show partial improvement in lung expansion, interstitial thickening, atelectasis, and cystic changes, although residual abnormalities may persist in severe disease.
Cause + Factors associated with BPD Increased risk Reduced risk or severity Prenatal: genetic susceptibility, maternal asthma, male sex Perinatal: lower gestational age, chorioamnionitis, intrauterine growth restriction Postnatal: mechanical ventilation, infection, inadequate nutrition Antenatal corticosteroids Surfactant therapy Lung-protective ventilation Avoidance of hypoxia and hyperoxia Adequate nutrition In premature infants, BPD develops when prenatal, perinatal, and postnatal exposures injure an immature lung and alter ongoing lung development. Inflammation, oxidative stress, and hypoxia contribute to acute lung injury, impairing alveolarization, vascularization, and airway growth. After injury, effective repair may allow for continued lung development, whereas abnormal remodeling can lead to chronic lung disease. The pattern of repair and remodeling is reflected in the parenchymal, airway, and vascular phenotypes of BPD. Genetic susceptibility may account for up to 50% of the variation in BPD severity. Inadequate postnatal nutrition may worsen lung injury and limit repair. Bronchopulmonary dysplasia has also been linked to alterations in the Wnt/beta-catenin pathway.
In the initial descriptions of BPD, prolonged high oxygen delivery and mechanical ventilation in premature infants caused necrotizing bronchiolitis and alveolar septal injury, with inflammation and scarring. Since the introduction of surfactant therapy, antenatal corticosteroids, and lung-protective ventilation strategies, a newer concept of BPD has emerged that instead focuses on impaired lung development manifesting as fewer alveoli, impaired septations, and variable interstitial thickening. Diagnosis The best way to define BPD is currently debated among experts. The simplest definition of BPD is based solely on whether respiratory support and/or oxygen therapy are required either at 28 days of life or 36 weeks' postmenstrual age. This definition does not account for the severity of disease, but is commonly used as an outcome in clinical trials.
The 2019 National Institute of Child Health and Human Development (US) definition classifies severity of BPD based on the amount and type of respiratory support required at 36 weeks' postmenstrual age:
No BPD: no respiratory support Mild (grade 1): nasal cannula ≤2 L/min Moderate (grade 2): nasal cannula >2 L/min or non-invasive positive pressure ventilation Severe (grade 3): invasive mechanical ventilation
Earlier criteria Since the term "bronchopulmonary dysplasia" was coined in 1967, several sets of criteria have been proposed. In 1979, BPD was defined by an oxygen requirement at 28 days of life, persistent chest radiograph abnormalities, and tachypnea with rales or retractions. In 1989, the Maternal and Child Health Bureau (US) proposed the following diagnostic criteria: Positive pressure ventilation during the first two weeks of life for a minimum of three days. Clinical signs of abnormal respiratory function. Requirements for supplemental oxygen for longer than 28 days of age to maintain PaO2 above 50 mm Hg. Chest radiograph with diffuse abnormal findings characteristic of bronchopulmonary dysplasia.
The 2006 National Institutes of Health (US) criteria for BPD (for neonates treated with >21% oxygen for at least 28 days) were: Mild: Breathing room air at 36 weeks' postmenstrual age or discharge for babies born before 32 weeks, or Breathing room air by 56 days' postnatal age or discharge for babies born after 32 weeks' gestation Moderate: Need for <30% oxygen at 36 weeks' postmenstrual age or discharge for babies born before 32 weeks, or Need for <30% oxygen to 56 days' postnatal age or discharge for babies born after 32 weeks' gestation Severe: Need for >30% oxygen, with or without positive pressure ventilation or continuous positive pressure at 36 weeks' postmenstrual age or discharge for babies born before 32 weeks, or Need for >30% oxygen with or without positive pressure ventilation or continuous positive pressure at 56 days' postnatal age or discharge for babies born after 32 weeks' gestation Management Management of BPD varies by disease phase (early, evolving, established) and severity (mild, moderate, severe). Broadly, this may include early preventive strategies during the first week of life, treatment of evolving disease before assessment at 36 weeks' postmenstrual age, and long-term care for established BPD after diagnosis.
Early prevention Management of BPD begins with strategies to prevent lung injury in preterm infants. These include minimizing intubation and mechanical ventilation when possible, and using lung-protective ventilation; lung-protective ventilation aims to reduce volutrauma (injury from excessive lung inflation), barotrauma (injury from excessive airway pressure), and oxygen-related lung injury. Oxygen therapy is adjusted to avoid both hypoxemia and oxygen toxicity.
Adequate nutrition is required to maintain lung growth and repair after birth. Infants with BPD often require increased energy intake to support growth and compensate for the increased work of breathing. Human breast milk feeding is associated with a lower risk of BPD in preterm infants.
Caffeine, usually given as caffeine citrate, is used to treat apnea of prematurity and may also help prevent BPD. Early administration, within the first three days of life, is associated with improved extubation success, shorter duration of mechanical ventilation, and improved lung function.
Vitamin A treatment in low birth weight babies may improve the 36-week mortality risk, decrease the days of mechanical ventilation, and decrease the incidence of BPD. Use of vitamin A is limited by the small size of the clinical benefit and the need for repeated painful intramuscular injections. It is not clear if treatment with superoxide dismutase supplementation is effective at preventing BPD or reducing mortality in preterm infants.
There is evidence that steroids like dexamethasone (systemic corticosteroid treatment) given to babies less than seven days old can prevent BPD. However, this treatment increases the risk of neurodevelopmental sequelae (e.g., cerebral palsy) and gastrointestinal perforation.
Evolving BPD Evolving BPD refers to the phase of disease after the first week of life and before assessment at 36 weeks' postmenstrual age. Respiratory management involves maintaining respiratory stability while avoiding prolonged intubation; non-invasive respiratory support (e.g., nasal CPAP) is preferred when possible.
For babies seven days old and older, "late systemic postnatal corticosteroid treatment" may reduce the risk of death and of BPD. There is some evidence that this treatment does not increase the risk of cerebral palsy; however, long-term studies considering the neurodevelopmental outcomes is needed to further understand the risk of this treatment option. Late systemic postnatal corticosteroid treatment is therefore generally reserved for babies seven days old or older who cannot be taken off of a ventilator. The benefits and risks of systemic corticosteroid treatment in older babies who are not intubated (on a ventilator) are not known.
Some infants with BPD may be treated with diuretics that decrease excess fluid in the lungs or with bronchodilators that relax the airway muscles to facilitate breathing. The use of diuretics and bronchodilators varies significantly between centers. Diuretic therapy is generally limited to infants with pulmonary edema or fluid overload who show clinical improvement with treatment. Bronchodilators have not been shown to reduce BPD or mortality, but may be used in selected infants with severe BPD who have asthma-like symptoms or reversible airway obstruction.
Hypercarbia (too much carbon dioxide [CO2] in the blood) may contribute to the development of BPD. In neonatal intensive care, CO2 monitoring is used to avoid both hypercarbia and hypocarbia (too little CO2 in the blood). Carbon dioxide can be monitored by taking a blood sample (arterial blood gas), through exhaled breath using capnography, or continuously through the skin using noninvasive transcutaneous CO2 monitors. The most effective and safest approach for measuring CO2 in newborn infants is not clear.
Established BPD