Bronchopulmonary dysplasia (BPD), a chronic lung disease of infancy, is among the most common and consequential complications associated with very preterm birth. Unfortunately, improvements in neonatal care over the past 2 to 3 decades have not resulted in lower rates of BPD among the highest risk infants. One of the ongoing debates in neonatal medicine is how best to define BPD to support the development of new therapies that prevent or treat the disease and to predict which infants are likely to experience adverse respiratory health in childhood.
Along with co-investigators from the Eunice Kennedy Shriver National Institute of Child Health and Human Development’s Neonatal Research Network, members of the Division of Neonatology at CHOP led a recent study that developed a new, evidence-based definition of BPD.1 Using a multicenter cohort of 2677 very preterm infants, our research team studied the prognostic accuracy of 18 potential definitions of BPD. Each definition used different combinations of the level of respiratory support and the amount of supplemental oxygen administered at 36 weeks postmenstrual age (PMA) to define the presence and severity of BPD. The goal of our research was to determine which evaluated definition best predicted the presence or absence of the following composite measure of childhood respiratory morbidity:
Death between 36 weeks postmenstrual age (PMA) and 2 years of age
Continued hospitalization for respiratory reasons at or beyond 50 weeks PMA
Use of supplemental oxygen, respiratory support, or respiratory monitoring (e.g., pulse oximeter, apnea monitor) at 2-year follow-up, or
≥2 re-hospitalizations for respiratory reasons prior to 2-year follow-up
The definition that best discriminated between infants with and without a poor respiratory outcome and those with and without moderate-severe neurodevelopmental impairment defined BPD according to mode of respiratory support administered at 36 weeks PMA, irrespective of prior or current oxygen therapy (see table at right). This new definition was more accurate for predicting adverse respiratory and neurodevelopmental outcomes in early childhood than the commonly used 2001 National Institutes of Health consensus definition and a definition proposed by a recent BPD workshop.
Historically, diagnostic criteria for BPD have relied heavily on the amount and duration of supplemental oxygen administered to very preterm infants. However, heterogeneity in oxygen administration and oxygen saturation targeting reduce the objectivity of these diagnostic criteria. Our data-driven approach showed that neither the use of supplemental oxygen for at least 28 days prior to 36 weeks PMA, nor assessment of the level of supplemental oxygen administered at 36 weeks PMA improved prognostic accuracy—once an infant’s disease severity was classified according to the mode of respiratory support prescribed at 36 weeks PMA. Removing the need to assess oxygen therapy altogether in this new definition may result in greater objectivity in the diagnosis of BPD.
This new definition also proposes another important change—the creation of a separate BPD severity level for infants treated with invasive respiratory support at 36 weeks PMA (grade 3 BPD). Relative to infants with less severe BPD, those with grade 3 BPD are 3 to 5 times more likely to undergo tracheostomy, utilize supplemental oxygen throughout the first 2 years of life, and experience significant and enduring deficits in motor function. 1 Greater recognition and increased research into this distinct subgroup may help improve long-term outcomes among this high-risk subset of infants.
Our research team continues to explore new ways to classify the presence and severity of BPD among very preterm infants. We are also focused on investigating promising therapies aimed at BPD prevention and treatment. One goal of our ongoing research is to define specific disease “phenotypes” in BPD to better individualize therapy selection. While that work is ongoing, we are hopeful that this new, evidence-based definition of BPD will support clinical care and research to improve respiratory outcomes in very preterm infants.