September 18, 2023

2 min read

Dargaville reports receiving personal fees from AbbVie and Chiesi Farmaceutici, surfactant at reduced cost and support for conference travel from Chiesi Farmaceutici during the conduct of the study, and owning a patent for a catheter design (USD752215S). Please see the study for all relevant financial disclosures.

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Key takeaways:

  • Minimally invasive surfactant therapy did not lower mortality among preterm infants with respiratory distress syndrome.
  • It did lower other secondary outcomes such as hospitalization and wheezing.

Minimally invasive surfactant therapy did not reduce a composite outcome of death and neurodevelopmental disability before age 2 years among preterm infants with respiratory distress syndrome who are on continuous positive airway pressure.

The results are from a 2-year follow-up of the OPTIMIST-A randomized controlled trial of minimally invasive surfactant therapy (MIST) conducted in 33 neonatal ICUs in 11 countries.


Data derived from Dargaville PA, et al. JAMA. 2023;doi: 10.1001/jama.2023.15694.

Although there was not a reduction in the “key” secondary outcome of composite death and moderate to severe neurodevelopmental disability (NDD), researchers did see a reduction in other secondary outcomes, including hospitalization for respiratory illness and wheezing.

Bronchopulmonary dysplasia, or BPD, the chronic disease of the preterm lung, has lasting effects on respiratory health in infancy and childhood and may be associated with a greater risk of neurodevelopmental disability throughout childhood and adolescence,” Peter A. Dargaville, MD, a pediatric physician at Royal Hobart Hospital in Hobart, Australia, and colleagues wrote in the study, which was published in JAMA.

Peter A. Dargaville

“It has been posited that interventions to reduce BPD frequency could produce lasting benefit on neurodevelopment and/or respiratory health,” they wrote.

MIST is the delivery of surfactant “via a thin catheter” and is “an emerging technique for spontaneously breathing preterm infants with respiratory distress syndrome,” the authors wrote. It “is known to improve survival without BPD in preterm infants,” they wrote.

The OPTIMIST-A trial compared MIST with sham treatment, and in relation to outcomes during first hospitalization.

The investigator-initiated, international, multicenter, blinded randomized control trial assessed data collected in 33 tertiary-level NICUs in Australia, Canada, Israel, New Zealand, Qatar, Singapore, Slovenia, the Netherlands, Turkey, the United Kingdom and the United States.

Infants were included if they were within a gestation range between 25 weeks and 28 weeks, 6 days, were admitted to a study center’s NICU, were supported with CPAP or noninvasive positive pressure ventilation for respiratory insufficiency without prior intubation, and needed a fraction of inspired oxygen of 0.3 or greater in the first 6 hours following birth.

Among 453 infants with follow-up data included in the study, 224 received MIST and 229 received sham treatment.

Ultimately, death or moderate to severe NDD occurred in 36.3% of infants in the MIST group and 36.1% of infants the control group. However, other secondary outcomes — which included the composite of death and moderate to severe NDD — did favor the MIST group, with hospitalization with respiratory illness occurring in 25.1% of the MIST group vs. 38.2% in the control group, and parent-reported wheezing or breathing difficult occurring in 40.6% of the MIST group vs. 53.6% in the control group.

“The effects of MIST on respiratory health in infancy appeared to be greater than on the outcome of BPD at 36 weeks’ postmenstrual age,” the authors wrote. “This finding bespeaks the difficulty of accurately quantifying the degree of lung injury in early life after preterm birth, with the current metrics of BPD being overly reductionist for this purpose.”

The authors speculated that infants in the study cohort without a diagnosis of BPD had a “lasting lung injury that manifested in early life with respiratory symptoms and rendered them vulnerable to respiratory infection.”

“Rates of respiratory symptoms and hospitalizations observed in other studies in the first 2 years in preterm infants without a BPD diagnosis would support this contention,” they wrote.

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