Two-Year Outcomes After Minimally Invasive Surfactant Therapy in Preterm Infants

Abstract

ImportanceThe 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.ObjectiveTo examine the effect of MIST on death or neurodevelopmental disability (NDD) at 2 years’ corrected age.Design, Setting, and ParticipantsFollow-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.InterventionsInfants 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 MeasuresThe 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.ResultsAmong 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 RelevanceIn 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 Registrationanzctr.org.au Identifier: ACTRN12611000916943

Outcomes After Minimally Invasive Surfactant Therapy in Preterm Infants

“…In the Discussion section of this study, the authors mentioned that the difference in the number of laryngoscopy procedures between the MIST group and the control group did not result in neurodevelopmental disability differences. However, the calculation method treating the Hobart method and traditional intubation as the same in terms of frequency does not align with clinical experience, given that the Hobart method results in shorter procedure times and less stress for the infants.…”

“…To the Editor A recent 2-year follow-up study of the OPTIMIST-A randomized clinical trial of preterm infants with respiratory distress syndrome found that MIST did not reduce the incidence of death or severe neurodevelopmental disability by 2 years of age. We have several concerns about the interpretation of this study’s results.…”

“…Nevertheless, it is plausible that this variance was associated with a decrease in adverse neurological outcomes attributed to apnea of prematurity in patients who received mechanical ventilation . The recent 2-year follow-up study did not mention the differences in apnea frequency between the 2 groups or the use of medications for apnea, which are factors worth further investigation.…”

Outcomes After Minimally Invasive Surfactant Therapy in Preterm Infants

“…To the Editor A recent 2-year follow-up study compared the effect of minimally invasive surfactant therapy (MIST) vs control (placebo) on neurodevelopment disability and death at 2 years’ corrected age.…”

Outcomes After Minimally Invasive Surfactant Therapy in Preterm Infants—Reply

“…In Reply Regarding our recent article reporting the 2-year outcomes after MIST in preterm infants, Drs Liu and Shi inquire why the BSID-IV was not used for assessment of neurodevelopmental disability. The explanation is that the BSID-IV was published in 2019, which was 5 years after the follow-up assessments were commenced for our study.…”