CLINICAL REPORT Surfactant-Replacement Therapy for Respiratory Distress in the Preterm and Term Neonate

Respiratory failure secondary to surfactant deficiency is a major cause of morbidity and mortality in preterm infants. Surfactant therapy substantially reduces mortality and respiratory morbidity for this population. Secondary surfactant deficiency also contributes to acute respiratory morbidity in late-preterm and term neonates with meconium aspiration syndrome, pneumonia/sepsis, and perhaps pulmonary hemorrhage; surfactant replacement may be beneficial for these infants. This statement summarizes indications, administration, formulations, and outcomes for surfactant-replacement therapy. The impact of antenatal steroids and continuous positive airway pressure on outcomes and surfactant use in preterm infants is reviewed. Because respiratory insufficiency may be a component of multiorgan dysfunction, preterm and term infants receiving surfactant-replacement therapy should be managed in facilities with technical and clinical expertise to administer surfactant and provide multisystem support. BACKGROUND Surfactant replacement was established as an effective and safe therapy for immaturity-related surfactant deficiency by the early 1990s.1–21 Systematic reviews of randomized, controlled trials have confirmed that surfactant replacement reduces initial inspired oxygen and ventilation requirements as well as the incidence of respiratory distress syndrome, death, pneumothorax, and pulmonary interstitial emphysema (Table 1).2–4,13 After the initial surfactant efficacy and safety trials were conducted, additional studies led to refinements in treatment strategies,5–7,10,11,13,22–36 choice of preparations,37–54 techniques for administration,55–65 and indications other than respiratory distress syndrome.66–87 The preponderance of evidence indicates that surfactant replacement increases survival rates without an increase in risk of disabilities. Thus, surfactant replacement is associated with an absolute increase in the number of preterm infants who survive with and without disabilities.88–112 However, the risk of long-term disability remains uncertain, because few follow-up studies at school age and adolescence for preterm infants treated with surfactant have been reported.* Antenatal steroid use to stimulate structural maturation and surfactant synthesis in the fetal lung increased significantly after completion of the pivotal surfactant trials.113–127 Investigations powered to assess the benefit of antenatal steroid exposure combined with surfactant replacement have not been reported, although secondary analyses of surfactant trials,113,114,116 animal studies,125–127 and clinical experience have indicated that, together, the 2 therapies have an additive effect. Preliminary studies of either continuous positive airway pressure alone or exogenous surfactants and rapid extubation to continuous positive airway pressure have suggested that the need for surfactant replacement and incidence of bronchopulmonary dysplasia in extremely preterm infants may be reduced.128–144 The purpose of this clinical report is to update and expand our previous statement about surfactant replacement in newborn infants.1 Specifically, the topics reviewed include efficacy in preterm infants, prophylactic versus rescue surfactant replacement, surfactant preparations and administration techniques, effects of surfactant on short-term and long-term outcomes, and surfactant replacement for respiratory disorders other than respiratory distress syndrome. The impact of antenatal steroid exposure and continuous positive airway *Refs 90, 93, 94, 101–103, 106, 107, and 111. www.pediatrics.org/cgi/doi/10.1542/ peds.2007-3283 doi:10.1542/peds.2007-3283 All clinical reports from the American Academy of Pediatrics automatically expire 5 years after publication unless reaffirmed, revised, or retired at or before that time. The guidance in this report does not indicate an exclusive course of treatment or serve as a standard of medical care. Variations, taking into account individual circumstances, may be appropriate.