Sex differences after NICU discharge in infants with BPD: Observations from one center

Nearly 50 years ago, Northway and colleagues at Stanford described the development of a new chronic lung disease in a group of premature infants who had respiratory distress syndrome after prolonged ventilation with high concentrations of oxygen and high peak inspiratory pressures. They coined the term bronchopulmonary dysplasia (BPD) to emphasize that both the airway and parenchyma of the lung tissues were affected. In the case definition, the infants all required oxygen at 28 days after birth and had progressive changes on chest radiograph that were graded in severity. The definition of BPD has evolved since its original clinical, radiographic, and pathologic description. With advances in care, more preterm infants needing oxygen at 28 days did not require its use in later weeks and before discharge. In 1988, Shennan and colleagues at Toronto retrospectively looked at pulmonary outcomes at age 2 in 606 infants born weighing less than 1500 grams. Infants with a normal pulmonary outcome came off supplemental oxygen at close to the same post-menstural age (PMA) despite the gestational age (GA) at which they were born. When the data was reviewed to look at pulmonary outcomes based on persistence of oxygen by PMA, specificity (the likelihood of those with a normal oxygen having no oxygen requirement) approached 90% at 36 weeks PMA. This important study shifted the concept of BPD from a clinical entity to a predictor of abnormal respiratory outcomes based on the use of supplemental oxygen at 36 weeks. Walsh et al. further refined the definition by requiring a room air challenge at 36 weeks PMA, and “physiologic BPD” was defined as failure to maintain a sustained oxygen saturation >90% when weaned off supplemental oxygen. Although a more recent NICHD/NHLBI Consensus Statement also incorporated gestational age and included levels of BPD severity, for practical purposes BPD is now defined as those infants who remain on supplemental oxygen at 36 weeks PMA. When you look at risk factors associated with the original clinical description, BPD occurred in late preterm infants whose lungs were severely affected by primitive mechanical ventilation and high oxygen levels. The use of antenatal corticosteroids and surfactant, along with a number of neonatal intensive care unit (NICU) strategies focused on reducing barotrauma and oxygen toxicity, resulted in the survival of very premature infants whose lungs are characterized not by fibrosis but instead by alveolar simplification with reduced surface area for gas exchange. In the modern era, gestational age is the risk factor most closely associated with BPD. Incidence of BPD increases with decreasing GA, with rates >50% in children born at less than 25 weeks GA. Antenatal factors, such as choriomanionitis and intrauterine growth restriction, as well as postnatal exposures, including infections and persistent patent ductus arteriosus, have consistently been associated with BPD. One particularly intriguing risk factor that has persisted over decades is male sex. Why premature male infants have higher rates of BPD is not understood, although the persistence of this sex difference despite tremendous advances in neonatal care and improved survival of premature infants has raised the possibility that there may