Two-Year Outcomes After Minimally Invasive Surfactant Therapy in Preterm Infants (OPTIMIST-A)

Key Points

Question For preterm infants with respiratory distress syndrome supported with continuous positive airway pressure (CPAP), does administration of surfactant via a thin catheter improve survival without moderate to severe neurodevelopmental disability (NDD) at 2 years of age compared with sham treatment?

Findings In this follow-up of a randomized clinical trial of 486 infants at 25 to 28 weeks’ gestation, the composite outcome of death or NDD at 2 years of age occurred in 36.3% receiving minimally invasive surfactant therapy compared with 36.1% receiving sham treatment.

Meaning In preterm infants supported with CPAP, minimally invasive surfactant therapy did not lead to a reduction in the composite outcome of death or neurodevelopmental disability at 2 years of age.

Abstract

Importance The long-term effects of surfactant administration via a thin catheter (minimally invasive surfactant therapy [MIST]) in preterm infants with respiratory distress syndrome remain to be definitively clarified.

Objective To examine the effect of MIST on death or neurodevelopmental disability (NDD) at 2 years’ corrected age.

Design, Setting, and Participants Follow-up study of a randomized clinical trial with blinding of clinicians and outcome assessors conducted in 33 tertiary-level neonatal intensive care units in 11 countries. The trial included 486 infants with a gestational age of 25 to 28 weeks supported with continuous positive airway pressure (CPAP). Collection of follow-up data at 2 years’ corrected age was completed on December 9, 2022.

Interventions Infants assigned to MIST (n = 242) received exogenous surfactant (200 mg/kg poractant alfa) via a thin catheter; those assigned to the control group (n = 244) received sham treatment.

Main Outcomes and Measures The key secondary outcome of death or moderate to severe NDD was assessed at 2 years’ corrected age. Other secondary outcomes included components of this composite outcome, as well as hospitalizations for respiratory illness and parent-reported wheezing or breathing difficulty in the first 2 years.

Results Among the 486 infants randomized, 453 had follow-up data available (median gestation, 27.3 weeks; 228 females [50.3%]); data on the key secondary outcome were available in 434 infants. Death or NDD occurred in 78 infants (36.3%) in the MIST group and 79 (36.1%) in the control group (risk difference, 0% [95% CI, −7.6% to 7.7%]; relative risk [RR], 1.0 [95% CI, 0.81-1.24]); components of this outcome did not differ significantly between groups. Secondary respiratory outcomes favored the MIST group. Hospitalization with respiratory illness occurred in 49 infants (25.1%) in the MIST group vs 78 (38.2%) in the control group (RR, 0.66 [95% CI, 0.54-0.81]) and parent-reported wheezing or breathing difficulty in 73 (40.6%) vs 104 (53.6%), respectively (RR, 0.76 [95% CI, 0.63-0.90]).

Conclusions and Relevance In this follow-up study of a randomized clinical trial of preterm infants with respiratory distress syndrome supported with CPAP, MIST compared with sham treatment did not reduce the incidence of death or NDD by 2 years of age. However, infants who received MIST had lower rates of adverse respiratory outcomes during their first 2 years of life.

Trial Registration anzctr.org.au Identifier: ACTRN12611000916943

JAMA. 2023;330(11):1054-1063. doi:10.1001/jama.2023.15694

https://jamanetwork.com/journals/jama/fullarticle/2809514