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Original Investigation
April 2016

Late Surfactant Administration in Very Preterm Neonates With Prolonged Respiratory Distress and Pulmonary Outcome at 1 Year of AgeA Randomized Clinical Trial

Author Affiliations
  • 1Maternite Regionale Universitaire, EA 3450 Devah, Université de Lorraine, Nancy, France
  • 2Hôpital de la Croix-Rousse, Hospices Civils de Lyon, Lyon, France
  • 3Assistance Publique-Hopitaux Marseille, Marseille, France
  • 4Centre Hospitalier Universitaire Rouen, Rouen, France
  • 5 Centre Hospitalier Universitaire Amiens, Amiens, France
  • 6 Centre Hospitalier Montreuil, Montreuil, France
  • 7Assistance Publique-Hopitaux Clamart, Clamart, France
  • 8Centre Hospitalier Arras, Arras, France
  • 9Centre Hospitalier Universitaire Caen, Caen, France
  • 10Centre Hospitalier Universitaire Tours, Tours, France
  • 11Centre Hospitalier Universitaire Lille, Lille, France
  • 12Assistance Publique-Hopitaux Paris Port Royal, Paris, France
  • 13Centre Hospitalier Universitaire Reims, Reims, France
  • 14Maternite Regionale Universitaire, EA 4360 APEMAC, Université de Lorraine, Nancy, France
JAMA Pediatr. 2016;170(4):365-372. doi:10.1001/jamapediatrics.2015.4617

Importance  Although immature neonate survival has improved, there is an increased risk of developing bronchopulmonary dysplasia, leading to significant respiratory morbidity. Measures to reduce bronchopulmonary dysplasia are not always effective or have important adverse effects.

Objective  To evaluate the effect of late surfactant administration in infants with prolonged respiratory distress on ventilation duration, respiratory outcome at 36 weeks’ postmenstrual age, and at 1 year postnatal age.

Design, Setting, and Participants  Double-blind randomized clinical trial at 13 level III French perinatal centers. Participants included 118 neonates at less than 33 weeks’ gestation who still required mechanical ventilation on day 14 (SD, 2) with fraction of inspired oxygen of more than 0.30. All survivors were eligible for follow-up. We performed an intent-to-treat analysis.

Interventions  Infants received 200 mg/kg of poractant alfa (surfactant) or air after randomization. At 1 year, after parents’ interview, infants underwent physical examination by pediatricians not aware of the randomization.

Main Outcomes and Measures  The duration of ventilation was the primary outcome. The combined outcome of death or bronchopulmonary dysplasia at 36 weeks’ postmenstrual age and respiratory morbidity at 1 year of age were the main secondary outcome measures.

Results  Of the 118 infants who participated in the study, 65 (55%) were male. Fraction of inspired oxygen requirements dropped after surfactant, but not air, for up to 24 hours after instillation (0.36 [0.11] vs 0.43 [0.18]; P < .005). Severe bronchopulmonary dysplasia/death rates at 36 weeks’ postmenstrual age were similar (27.1% vs 35.6%; P = .32). Less surfactant-treated infants needed rehospitalization for respiratory problems after discharge (28.3% vs 51.1%; P = .03); 39.5% vs 50% needed respiratory physical therapy (P = .35). No difference was observed for weight (7.8 [1.2] kg vs 7.6 [1.1] kg), height (69 [5] cm vs 69 [3] cm), and head circumference (44.4 [1.7] cm vs 44.2 [1.7] cm) measured at follow-up, nor for neurodevelopment outcome.

Conclusions and Relevance  Late surfactant administration did not alter the early course of bronchopulmonary dysplasia. However, surfactant-treated infants had reduced respiratory morbidity prior to 1 year of age.

Trial Registration  clinicaltrials.gov Identifier: NCT01039285