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

Abstract

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: ClinicalTrials.gov: NCT01022580.

Keywords: bronchopulmonary dysplasia; prematurity; pulmonary morbidity; wheeze.

Figure 1

(online only): Patient flow diagram. Deaths and study withdrawals prior to neonatal discharge detailed in Ballard et al, 2016 (13).

Figure 2

Proportion of infants with respiratory resource utilization at each survey time point, 3, 6, 9 and 12 months corrected age, in late surfactant and control groups: A, Total resource utilization, B, Respiratory medication exposure, C, Home respiratory support, D, Hospitalization for respiratory cause, and E, Diuretic, F, Bronchodilator, G, Inhaled corticosteroid and H, Systemic steroid exposure.