Surfactant Administration in Preterm Infants: Drug Development Opportunities

J Pediatr. 2019 May;208:163-168. doi: 10.1016/j.jpeds.2018.11.041. Epub 2018 Dec 21.


Objective: To evaluate how frequently surfactant is used off-label in preterm infants.

Study design: We conducted a retrospective cohort analysis of prospectively collected administrative data for 2005-2015 from 348 neonatal intensive care units in the US. We quantified off-label administration of poractant alfa, calfactant, or beractant in inborn infants born at <37 weeks of gestational age (GA). Off-label surfactant administration was defined according to the Food and Drug Administration (FDA) label.

Results: Of a total of 110 822 preterm infants who received surfactant, 68 226 (62%) received the surfactant off-label. The majority of infants who received surfactant off-label had a higher birth weight than those who received surfactant on-label (40 716 [37%]), had an older GA than those who received surfactant on-label (35 191 [32%]), or were treated with intubation and surfactant administration followed by immediate extubation (INSURE) (32 310 [29%]). Poractant alfa was administered via INSURE more frequently than beractant or calfactant (16 688 [38%], 7137 [20%], and 8485 [27%], respectively). An increasing number of infants received surfactant via INSURE from 2005 to 2015 (from 1697 [19%] to 3368 [36%]).

Conclusions: The majority of surfactant given to preterm infants is administered off-label. The uptrend in administration via INSURE coincides with increased supporting evidence. The gap between FDA labeling and current clinic practice exemplifies an opportunity for label expansion, which may require additional prospective or retrospective safety and/or effectiveness data for infants of older GA and higher birth weight.

Keywords: drug development; surfactant.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Biological Products / administration & dosage*
  • Birth Weight
  • Drug Industry / trends
  • Drug Labeling
  • Electronic Health Records
  • Female
  • Gestational Age
  • Humans
  • Infant, Newborn
  • Infant, Premature
  • Infant, Premature, Diseases / drug therapy
  • Intensive Care, Neonatal*
  • Male
  • Off-Label Use
  • Phospholipids / administration & dosage*
  • Pulmonary Surfactants / administration & dosage*
  • Respiratory Distress Syndrome, Newborn / prevention & control
  • Retrospective Studies
  • United States
  • United States Food and Drug Administration


  • Biological Products
  • Phospholipids
  • Pulmonary Surfactants
  • poractant alfa
  • calfactant
  • beractant