Surfactant Treatment—A National, Population-Based Study of Adherence to Best Practice, Off-Label Use, and Associations With Outcomes | Neonatology | JAMA Network Open | JAMA Network
[Skip to Navigation]
Sign In
Invited Commentary
May 5, 2021

Surfactant Treatment—A National, Population-Based Study of Adherence to Best Practice, Off-Label Use, and Associations With Outcomes

Author Affiliations
  • 1Department of Pediatrics, LAC+USC Medical Center, Keck School of Medicine of USC, Los Angeles, California
JAMA Netw Open. 2021;4(5):e217848. doi:10.1001/jamanetworkopen.2021.7848

Respiratory distress syndrome (RDS) is primarily due to surfactant deficiency in preterm infants. Surfactant treatment is the standard of care in preterm neonates with RDS. Surfactant therapy has been shown to decrease pneumothorax and improve newborn and infant survival.1 Timing of surfactant administration, fraction of inspired oxygen (FIO2) criteria for first dose of surfactant, and method of surfactant administration using a thin catheter or an endotracheal tube are evolving after more than 3 decades of using surfactant in preterm infants.2,3 The study by Challis et al4 describes different surfactant strategies, such as early surfactant (within 2 hours of birth), off-label use, and no treatment when it was indicated, and examines outcomes associated with these strategies using a large population-based cohort from Sweden. The study population was a more recent cohort of newborns born between 2009 and 2019, making the findings from this study more relevant to current practice. Surfactant used in this population was limited to porcine surfactant, poractant alfa. Studies comparing porcine vs bovine surfactants have shown better outcomes with porcine surfactant, especially when a higher initial dose of 200 mg/kg was used.5,6

In the study by Challis et al,4 early rescue treatment within 2 hours of birth was associated with lower odds for pneumothorax, severe grades of intraventricular hemorrhage, and need for postnatal corticosteroid use and with shorter duration of mechanical ventilation, which are consistent with previous studies. However, the Challis et al4 found lower survival in infants treated earlier. It is likely that preterm infants who were intubated for respiratory failure or had more severe RDS were treated earlier, accounting for this increased mortality. In term infants with meconium aspiration syndrome (MAS), surfactant treatment was not associated with improved outcomes. This may be owing to the small number patients with MAS in the study by Challis et al.4 A 2021 randomized clinical trial by González et al7 that enrolled 100 term neonates with MAS and hypoxemic respiratory failure treated with porcine surfactant in combination with inhaled nitric oxide found a significant reduction in the combined outcome of death or need for extracorporeal membrane oxygenation.

Limitations in the study by Challis et al4 include lack of data on the method of surfactant administration. For example, in a systematic review, Aldana-Aguirre et al8 reported that a less invasive surfactant administration technique, compared with the intubation, surfactant, extubation technique for surfactant delivery in preterm infants, was associated with less bronchopulmonary dysplasia, less of a composite outcome of bronchopulmonary dysplasia or death at 36 weeks, and less need for invasive mechanical ventilation.

The findings by Challis and colleagues4 provide a strong rationale to use this extensively studied treatment of RDS with surfactant as an early rescue therapy within 2 hours of birth when preterm infants are receiving FIO2 of 0.30 or greater to improve overall outcomes.

Back to top
Article Information

Accepted for Publication: March 20, 2021.

Published: May 5, 2021. doi:10.1001/jamanetworkopen.2021.7848

Correction: This article was corrected on July 23, 2021, because it incorrectly stated that study by Challis et al4 did not report data on oxygen requirement at 36 weeks postmenstrual age.

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2021 Ramanathan R. JAMA Network Open.

Corresponding Author: Rangasamy Ramanathan, MBBS, MD, DCH, Department of Pediatrics, LAC+USC Medical Center, Keck School of Medicine of USC, 1200 N State St, IRD-820, Los Angeles, CA 90033 (

Conflict of Interest Disclosures: Dr Ramanathan reported receiving grants from Chiesi Farmaceutici.

Sardesai  S, Biniwale  M, Wertheimer  F, Garingo  A, Ramanathan  R.  Evolution of surfactant therapy for respiratory distress syndrome: past, present, and future.   Pediatr Res. 2017;81(1-2):240-248. doi:10.1038/pr.2016.203PubMedGoogle ScholarCrossref
Polin  RA, Carlo  WA; Committee on Fetus and Newborn; American Academy of Pediatrics.  Surfactant replacement therapy for preterm and term neonates with respiratory distress.   Pediatrics. 2014;133(1):156-163. doi:10.1542/peds.2013-3443PubMedGoogle ScholarCrossref
Sweet  DG, Carnielli  V, Greisen  G,  et al.  European consensus guidelines on the management of respiratory distress syndrome—2019 update.   Neonatology. 2019;115(4):432-450. doi:10.1159/000499361PubMedGoogle ScholarCrossref
Challis  P, Nydert  P, Håkansson  S, Norman  M.  Association of adherence to surfactant best practice uses with clinical outcomes among neonates in Sweden.   JAMA Netw Open. 2021;4(5):e217269. doi:10.1001/jamanetworkopen.2021.7269Google Scholar
Singh  N, Halliday  HL, Stevens  TP, Suresh  G, Soll  R, Rojas-Reyes  MX.  Comparison of animal-derived surfactants for the prevention and treatment of respiratory distress syndrome in preterm infants.   Cochrane Database Syst Rev. 2015;(12):CD010249. doi:10.1002/14651858.CD010249.pub2PubMedGoogle Scholar
Tridente  A, De Martino  L, De Luca  D.  Porcine vs bovine surfactant therapy for preterm neonates with RDS: systematic review with biological plausibility and pragmatic meta-analysis of respiratory outcomes.   Respir Res. 2019;20(1):28. doi:10.1186/s12931-019-0979-0PubMedGoogle ScholarCrossref
González  A, Bancalari  A, Osorio  W,  et al.  Early use of combined exogenous surfactant and inhaled nitric oxide reduces treatment failure in persistent pulmonary hypertension of the newborn: a randomized controlled trial.   J Perinatol. 2021;41(1):32-38. doi:10.1038/s41372-020-00777-xPubMedGoogle ScholarCrossref
Aldana-Aguirre  JC, Pinto  M, Featherstone  RM, Kumar  M.  Less invasive surfactant administration versus intubation for surfactant delivery in preterm infants with respiratory distress syndrome: a systematic review and meta-analysis.   Arch Dis Child Fetal Neonatal Ed. 2017;102(1):F17-F23. doi:10.1136/archdischild-2015-310299PubMedGoogle ScholarCrossref
Limit 200 characters
Limit 25 characters
Conflicts of Interest Disclosure

Identify all potential conflicts of interest that might be relevant to your comment.

Conflicts of interest comprise financial interests, activities, and relationships within the past 3 years including but not limited to employment, affiliation, grants or funding, consultancies, honoraria or payment, speaker's bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued.

Err on the side of full disclosure.

If you have no conflicts of interest, check "No potential conflicts of interest" in the box below. The information will be posted with your response.

Not all submitted comments are published. Please see our commenting policy for details.

Limit 140 characters
Limit 3600 characters or approximately 600 words