The Randomized, Controlled Trial of Late Surfactant: Effects on Respiratory Outcomes at 1-Year Corrected Age

Roberta L. Keller, Eric C. Eichenwald, Anna Maria Hibbs, Elizabeth E. Rogers, Katherine C. Wai, Dennis M. Black, Philip L. Ballard, Jeanette M. Asselin, William E. Truog, Jeffrey D. Merrill, Mark C. Mammel, Robin H. Steinhorn, Rita M. Ryan, David J. Durand, Catherine M. Bendel, Ellen M. Bendel-Stenzel, Sherry E. Courtney, Ramasubbareddy Dhanireddy, Mark L. Hudak, Frances R. KochDennis E. Mayock, Victor J. McKay, Jennifer Helderman, Nicolas F. Porta, Rajan Wadhawan, Lisa Palermo, Roberta A. Ballard

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13 Scopus citations


Objective To determine the effects of late surfactant on respiratory outcomes determined at 1-year corrected age in the Trial of Late Surfactant (TOLSURF), which randomized newborns of extremely low gestational age (≤28 weeks' gestational age) ventilated at 7-14 days to late surfactant and inhaled nitric oxide vs inhaled nitric oxide-alone (control). Study design Caregivers were surveyed in a double-blinded manner at 3, 6, 9, and 12 months' corrected age to collect information on respiratory resource use (infant medication use, home support, and hospitalization). Infants were classified for composite outcomes of pulmonary morbidity (no PM, determined in infants with no reported respiratory resource use) and persistent PM (determined in infants with any resource use in ≥3 surveys). Results Infants (n = 450, late surfactant n = 217, control n = 233) were 25.3 ± 1.2 weeks' gestation and 713 ± 164 g at birth. In the late surfactant group, fewer infants received home respiratory support than in the control group (35.8% vs 52.9%, relative benefit [RB] 1.28 [95% CI 1.07-1.55]). There was no benefit of late surfactant for No PM vs PM (RB 1.27; 95% CI 0.89-1.81) or no persistent PM vs persistent PM (RB 1.01; 95% CI 0.87-1.17). After adjustment for imbalances in baseline characteristics, relative benefit of late surfactant treatment increased: RB 1.40 (95% CI 0.89-1.80) for no PM and RB 1.24 (95% CI 1.08-1.42) for no persistent PM. Conclusion Treatment of newborns of extremely low gestational age with late surfactant in combination with inhaled nitric oxide decreased use of home respiratory support and may decrease persistent pulmonary morbidity. Trial registration NCT01022580

Original languageEnglish (US)
Pages (from-to)19-25.e2
JournalJournal of Pediatrics
StatePublished - Apr 1 2017

Bibliographical note

Funding Information:
TOLSURF was funded by National Heart, Lung, and Blood Institute (NHLBI; U01 HL094338, U01 HL094355, and UL1 TR000004 [to K.W.]). The NHLBI Scientific Officer, Carol Blaisdell, MD, was present and participated in all Steering Committee meetings as a nonvoting member. Ikaria Inc and ONY Inc provided drugs for the conduct of the trial but had no input into study design, data analysis, data interpretation or manuscript preparation. R.S. serves as Associate Editor of The Journal of Pediatrics. The other authors declare no conflicts of interest.


  • bronchopulmonary dysplasia
  • prematurity
  • pulmonary morbidity
  • wheeze

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