Two-Year Outcomes After Minimally Invasive Surfactant Therapy in Preterm Infants
Authors: Dargaville Peter A. , Kamlin C. Omar F. , Orsini Francesca , Wang Xiaofang , De Paoli Antonio G. , Kanmaz Kutman H. Gozde , Cetinkaya Merih , Kornhauser-Cerar Lilijana , Derrick Matthew , Özkan Hilal , Hulzebos Christian V. , Schmölzer Georg M. , Aiyappan Ajit , Lemyre Brigitte , Kuo Sheree , Rajadurai Victor S. , O’Shea Joyce , Biniwale Manoj , Ramanathan Rangasamy , Kushnir Alla , Bader David , Thomas Mark R. , Chakraborty Mallinath , Buksh Mariam J. , Bhatia Risha , Sullivan Carol L. , Shinwell Eric S. , Dyson Amanda , Barker David P. , Kugelman Amir , Donovan Tim J. , Goss Kevin C. W. , Tauscher Markus K. , Murthy Vadivelam , Ali Sanoj K. M. , Clark Howard W. , Soll Roger F. , Johnson Samantha , Cheong Jeanie L. Y. , Carlin John B. , Davis Peter G. ,   OPTIMIST-A Trial Investigators, Darlow Brian A , Dunn Michael , Salter Amy , Butterley Karen , Stephens Nicky , Reid Lizzy , Dunn Ross , Stephens Luke , Matzolic Tammy , Argus Brenda , Twitchell Emily , Barrotta Joanna , Noble Elizabeth , Tan Kenneth , Yeomans Emma , Lai Melissa , Koorts Pieter , Broom Margaret , Law Brenda , Cheung Po-Yin , Van Os Sylvia , Fray Caroline , Huneault-Purney Nicole , Faulkner Melissa , Horth Chantal , Grimwood Rebecca , Riskin A , Kalinina Tatiana , Tsafrir C , Afuta S , Timstut Fanny , Huth Sabine , McCaffrey Frances , Hummler Helmut , Gupta Samir , Dinan Mary , Casiraghi Miriam , Yan Yip Wai , Gopagondanahalli Krishna R , Chandran Suresh , Dela Puerta Rowena , Lučovnik Miha , Kurtovič Vlasta L , Olthuis Annelies J , Baptist Dyvonne H , Bouma Helene A , Büyüktiryaki Mehmet , Sahin Suzan , Cebeci Burcu , Ozdemir Sule , Vantansever Aylin , McKay Lorna , McSorley Therese , Crowley Philippa , Pond Jenny , Mellish Christie , Hayward Rachel M , Morris Ian P , Elliot Sian , Patel Deena-Shefali , Andrzejewska Izabela , Cook Amanda , Wolf Sue , Tong Micah , Ericksen Rosanna , Logan Amanda , Niblack Patricia , Tauscher Zenaida R , Whitlow Pamela 
Published: September 2023

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