The disease that has defined the history of neonatology is what we now call respiratory distress syndrome (RDS). The enigmatic hyaline membrane disease was uniformly fatal for preterm infants before neonatal care was available.1 The atelectasis, epithelial injury, and accumulation of eosinophilic proteinaceous material in the airspaces were attributed primarily to aspiration or infection. The recognition that the early respiratory failure of some preterm infants could be treated with oxygen in the 1950s contributed to the development of early newborn care centers that have morphed into modern neonatal intensive care units. However, excessive oxygen use resulted in an epidemic of retrolental fibroplasia (now called retinopathy of prematurity).2
The seminal 1959 observation of Avery and Mead3 that the lungs of preterm infants who died of hyaline membrane disease had decreased amounts of surfactant finally identified the primary abnormality that caused the respiratory failure. However, little progress in treatment other than oxygen occurred until the invention of continuous positive airway pressure (CPAP) by Gregory et al4 in 1971 and the concurrent development of mechanical ventilators with positive end-expiratory pressure (PEEP) for infants. Maternal treatment with corticosteroids was described by Liggins and Howie5 in 1972 and to date is the only therapy to prevent RDS. In 1971, Gluck et al6 reported that the L/S (lecithin/sphingomyelin) ratio, a test to measure surfactant components in amniotic fluid, could predict infants at risk of RDS prior to birth. These advances, together with improvements in the general care for preterm infants (better temperature control, fluid therapy, nutrition, physiological monitoring) resulted in high survival rates for the larger and more mature preterm infants, but with the appearance of a new lung disease—bronchopulmonary dysplasia (BPD), caused primarily by oxygen and mechanical ventilation.7 With increased survival, the name of the disease changed from the signature pathologic finding—the hyaline membrane to the physiologic descriptor—respiratory distress.
Experimental studies with premature animals demonstrated that surfactant given via the trachea could improve lung function,8,9 and the first report of successful surfactant treatment of RDS was published in 1980 by Fujiwara et al.10 Surfactants were licensed for general clinical use in 1999–2000 by the Food and Drug Administration (FDA). Subsequent technological improvements in infant ventilators, in the general care of very preterm infants, and in physician skills for the treatment of RDS have resulted in remarkable survival rates with minimal complications for infants with RDS who are greater than 28 weeks’ gestational age at birth.11 Thus, the epidemiology of RDS has changed as the recognition and treatment of the disease has evolved.
In the current era, about 500,000 preterm infants are born in the United States each year, representing about 13% of all live births. Most of these infants are late-preterm infants born between 35 and 37 weeks’ gestational age who have an increased incidence of transient tachypnea of the newborn (TTN) but about a 1% ...