The Genetics of Bronchopulmonary Dysplasia

Over the last 15 years, neonatal morbidity and mortality has changed little for very low birth weight babies despite significant technological and therapeutic advances. Bronchopulmonary dysplasia (BPD) continues to be a major problem despite antenatal steroid use, surfactant replacement therapy, gentle noninvasive ventilation techniques, permissive hypercarbia, and judicious use of oxygen. Current evidence supports multiple contributing factors. Prematurity is the cardinal factor; others include pulmonary baro/volutrauma, hyperoxia, and inflammation. BPD is an end product of pulmonary inflammatory response and lung repair with impaired alveolarization and vascularization in response to lung injury. These sequences involve multiple morphoregulatory molecules, which have a range of activities largely determined by genetic variability. A clearer understanding of genetic susceptibility for BPD has recently emerged. Twin studies have shown that the BPD status of one twin, even after correcting for contributing factors, is a highly significant predictor of BPD in the second twin. After controlling for covariates, genetic factors account for 53% (P = 0.004, 95% CI = 16%–89%) of the variance in liability for BPD. Incremental improvements will likely depend on identification of these genetic components for targeting specific therapies.