Pulmonary hemorrhage in premature infants after treatment with synthetic surfactant: An autopsy evaluation

In an across study analysis of five multicenter, placebo-controlled trials of the synthetic surfactant, Exosurf Neonatal in infants weighing at least 700 gm, the incidence of clinical pulmonary hemorrhage was 1.9% in treated infants and 1.0% in control infants. To investigate whether a similar increase was also present histologically at postmortem examination, a blinded retrospective review of all autopsy reports from infants dying during these five trials was conducted. Pulmonary hemorrhage was present in 55% of 159 infants undergoing autopsy; the incidence was not different in infants treated with surfactant or air placebo. Birth weight was inversely related to the incidence of pulmonary hemorrhage in both groups. Pulmonary pathologic findings significantly associated with pulmonary hemorrhage included pulmonary interstitial emphysema and necrotizing laryngotracheitis in both groups. In the surfactant group, patent ductus arteriosus, intraventricular hemorrhage, and pneumothorax were significantly more frequent among those who developed pulmonary hemorrhage. In contrast to clinical diagnosis, pathologic diagnosis of pulmonary hemorrhage at autopsy was not more common in infants treated with Exosurf Neonatal.