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Giving Oropharyngeal Surfactant at Birth Is No Help to Preemies

— Increased rates of pneumothorax emerged among newborns treated prophylactically

MedpageToday
A photo of an infant receiving mechanical ventilation in the intensive care unit.

There was no less need for intubation among newborns born preterm who were given prophylactic oropharyngeal surfactant at birth to ward off respiratory failure, a randomized clinical trial found.

Infants randomized to continuous positive airway pressure (CPAP) therapy with or without oropharyngeal surfactant therapy shared similar rates of being intubated within 120 hours for persistent apnea, bradycardia, or respiratory failure (63.5% vs 64.8%, relative risk 0.98, 95% CI 0.81-1.18), reported Colm O'Donnell, MB, PhD, of the National Maternity Hospital in Dublin, Ireland, and co-authors.

Additionally, a significantly greater proportion of infants in the surfactant cohort were ultimately diagnosed and treated for pneumothorax than control infants (16.6% vs 6.4%, P=0.04), according to the POPART trial published in .

"These findings suggest that administration of surfactant into the oropharynx immediately after birth in addition to CPAP should not be routinely used," the authors concluded, though they speculated that "the lack of efficacy in our study was due to insufficient surfactant reaching the lungs."

"In our study, we were uncertain about how much surfactant was aspirated and speculate that it may have been highly variable among newborns," O'Donnell's group noted.

Exogenous surfactant can be administered in various ways to fill the need for surfactant in neonatal respiratory distress syndrome (RDS). Avoiding laryngoscopy and sedatives, the intervention tested in POPART had surfactant instilled into the newborn's oropharynx via a flexible thin catheter as soon as possible after delivery and before CPAP initiation. The surfactant was given from 30 to 60 seconds, ideally before the umbilical cord was clamped.

David Rub, MD, and Nicolas Bamat, MD, MSCE, both of the Perelman School of Medicine at the University of Pennsylvania in Philadelphia, noted that the results of the trial, while important, should be interpreted with caution.

"First, the POPART trial chose to administer surfactant prior to initial resuscitation and lung recruitment with CPAP," the pair wrote in . "It is unclear whether oropharyngeal surfactant was not beneficial in this nonselective population due to insufficient surfactant reaching the lungs, interference with early CPAP resuscitation either by delaying CPAP initiation or obstructing CPAP transmission in the oropharynx, or simply lacking net benefit despite successful delivery."

The pair also suggested that the finding of increased pneumothorax supports the theory that the administered surfactant was not aspirated consistently by the newborns, resulting in "regional hyperinflation and air leak."

"Despite the results of the study indicating no reduction in the rate of intubation in the first 5 days of life, to our knowledge, the POPART trial represents the first rigorous foray into an attractive surfactant administration method and provides valuable information to the neonatology community," Rub and Bamat nevertheless wrote. "The avoidance of laryngoscopy, sedative medications, and specialized equipment makes this method enticing, particularly in resource-limited settings. Further investigation of oropharyngeal surfactant is warranted."

The trial included 251 participants born prior to 29 weeks gestational age (GA). It was conducted at nine medical centers in Ireland, Norway, the Czech Republic, Belgium, Sweden, and Portugal from 2017 to 2020. Patients were randomized to oropharyngeal surfactant treatment followed by CPAP or CPAP therapy alone. In the intervention group, newborns who were under 26 weeks GA received a 120-mg vial of the surfactant and newborns who were 26-28 weeks, plus an additional 6 days of gestation, received a 240-mg vial.

The study cohort averaged 26 weeks GA at enrollment and included slightly more boys than girls. Birth weight was a mean 858 g and 829 g, respectively, for the surfactant and control groups.

O'Donnell's group cited the inability to blind both outcome assessors and caregivers as the primary limitation of the study.

Researchers also noted that POPART was unique in its randomization of patients prior to delivery, which may have affected the results for prophylactic oropharyngeal surfactant therapy.

Previous work had shown that less invasive surfactant administration (LISA) was tied to good outcomes for extremely preterm infants with potential respiratory distress syndrome.

"Future trials should focus on selective rather than prophylactic use, identifying preterm populations most likely to benefit based on clinical respiratory thresholds, and comparing the effectiveness of oropharyngeal administration with LISA and [minimally invasive surfactant therapy] or [intubation-surfactant-extubation], depending on the standard practice in that setting," Rub and Bamat urged.

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    Elizabeth Short is a staff writer for MedPage Today. She often covers pulmonology and allergy & immunology.

Disclosures

This study was supported by the European Union Framework Programme for Research and Innovation Horizon 2020 funded by the Paediatric Clinical Research Infrastructure Network, Chiesi Farmaceutici, and the National Children's Research Centre.

O'Donnell, Rub, and Bamat had no disclosures.

Primary Source

JAMA Pediatrics

Murphy MC, et al "Prophylactic oropharyngeal surfactant for preterm newborns at birth: A randomized clinical trial" JAMA Pediatr 2023; DOI: 10.1001/jamapediatrics.2023.5082.

Secondary Source

JAMA Pediatrics

Rub DM, Bamat NA "Lack of effect for oropharyngeal surfactant for preterm neonates: Method or timing? JAMA Pediatr 2023; DOI: 10.1001/jamapediatrics.2023.5079.