Minimally invasive surfactant therapy (MIST) did not reduce mortality or neurodevelopmental disability (NDD) risk in children 2 years of age who were born preterm with respiratory distress syndrome and received continuous positive airway pressure (CPAP) therapy, according to study results published in Journal of the American Medical Association.
Researchers investigated outcomes of MIST in 2-year-old children (corrected age) born preterm with respiratory distress syndrome who were receiving CPAP therapy, comparing this intervention with sham treatment. Primary outcomes of interest were the incidence of death or moderate to severe NDD at 2-years corrected age; the effect of MIST vs sham treatment on adverse respiratory outcomes was also assessed.
The researchers conducted a follow-up study of OPTIMIST-A (ClinicalTrials.gov Identifier: NCT02140580), a randomized clinical trial of 486 infants with a gestational age of 25 to 28 weeks who were admitted to the neonatal intensive care unit for respiratory insufficiency and were subsequently intubated. Infants with another respiratory disease or serious congenital disorder were excluded from the study. Children treated with MIST (n=242) received a dose of 200 mg/kg poractant alfa intratracheally; children in the control group (n=244) received a sham treatment (ie, transient repositioning only).
Outcome data was collected via in-person follow-up assessment at 2 years corrected age, with an online questionnaire administered for children who were unable to do an in-person follow-up. NDD was defined as moderate to severe cognitive or language impairment, cerebral palsy equivalent to the Gross Motor Function Classification System level of 2 or higher, visual impairment, or hearing impairment. Relative risk (RR) was calculated to compare poractant alfa treatment with the sham treatment and was adjusted for gestational age.
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.
Researchers found that 29 infants treated with MIST and 24 infants treated with sham treatment died at 2 years corrected age. Although the RR of death between the treatment and control group was 1.23, it was insignificant (95% CI, 0.69-2.19; P =.48). The relative difference (RD) in death between the 2 groups was also insignificant (RD, 2.4%; 95% CI, -3.6% to 8.4%).
Among the children who survived, 186 in the MIST group and 195 in the control group were fully assessed for NDD at 2 years corrected age. NDD occurred in 49/186 of children in the MIST group and 55/195 children in the control group. The RR and RD of developing NDD was also insignificant by 2 years corrected age (RR, 0.94; 95% CI, 0.71-1.25; RD, -1.6%; 95% CI, -9.4% to 6.2%; P =.69).
Notably, infants treated with MIST had a significantly lower relative reduction of 34% in the frequency of 1 or more hospitalizations for respiratory illness than the control group (MIST group vs control group, 25.1% vs 38.2%; RR, 0.66; 95% CI, 0.54-0.81; P <.001). Infants treated with MIST also had a 24% relative reduction in wheezing or breathing difficulty, compared with the control group (MIST group vs control group, 40.6% vs 53.6%; RR, 0.76; 95% CI, 0.63-0.90; P =.002).
Study limitations include use of an online questionnaire as the dominant method of data collection and the limited sample size. Additionally, the original clinical trial was not designed to detect differences in 2-year outcomes or to assess some of the comparisons made in this follow-up study.
Overall, researchers concluded that “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.”