European Journal of Pediatrics

, Volume 175, Issue 12, pp 1933–1942 | Cite as

Surfactant instillation in spontaneously breathing preterm infants: a systematic review and meta-analysis

  • Vincent RigoEmail author
  • Caroline Lefebvre
  • Isabelle Broux
Original Article


Less invasive surfactant therapies (LIST) use surfactant instillation through a thin tracheal catheter in spontaneously breathing infants. This review and meta-analysis investigates respiratory outcomes for preterm infants with respiratory distress syndrome treated with LIST rather than administration of surfactant through an endotracheal tube. Randomised controlled trial (RCT) full texts provided outcome data for bronchopulmonary dysplasia (BPD), death or BPD, early CPAP failure, invasive ventilation requirements and usual neonatal morbidities. Relative risks (RR) from pooled data, with subgroup analyses, were obtained from a Mantel-Haenszel analysis using a random effect model. Six RCTs evaluated LIST: 4 vs InSurE and 1 each vs delayed or immediate intubation for surfactant. LIST resulted in decreased risks of BPD (RR = 0.71 [0.52–0.99]; NNT = 21), death or BPD (RR = 0.74 [0.58–0.94]; NNT = 15) and early CPAP failure or invasive ventilation requirements (RR = 0.67 [0.53–0.84]; NNT = 8 and RR = 0.69 [0.53–0.88]; NNT = 6). Compared to InSurE, LIST decreased the risks of BPD or death (RR = 0.63 [0.44–0.92]; NNT = 11) and of early CPAP failure (RR = 0.71 [0.53–0.96]; NNT = 11). Common neonatal morbidities were not different.

Conclusions: Respiratory management with LIST decreases the risks of BPD and BPD or death, and the need for invasive ventilation. This strategy appears safe, but long-term follow-up is lacking.

What is Known:

Initial management of preterm infants with CPAP decreases the risk of death or BPD, but many still require surfactant or invasive ventilation.

Surfactant can be instilled through a tracheal thin catheter while the infant breathes on CPAP, but improvement in BPD is inconsistent between studies.

What is New:

Less invasive surfactant therapy (LIST) strategies decrease the risks of BPD, of death or BPD, and of CPAP failure compared to strategies where surfactant is administered through an endotracheal tube.

LIST strategies decrease the risks of the composite outcome of BPD or death and of early CPAP failure when compared to “intubation-surfactant-extubation” approaches.


Less/minimally invasive surfactant Preterm infant Respiratory distress syndrome Bronchopulmonary dysplasia Meta-analysis 



Avoidance of Mechanical Ventilation Study


Bronchopulmonary dysplasia (here: moderate to severe)


Cystic periventricular leucomalacia




Intraventricular haemorrhage


Less invasive surfactant administration


Less invasive surfactant therapy


Mechanical ventilation


Minimally invasive surfactant therapy


Nasal continuous positive airway pressure


Necrotising enterocolitis


Numbers needed to treat/to harm


Nonintubated Surfactant Application Study


Patent ductus arteriosus


Randomised controlled trial


Retinopathy of prematurity


Relative risk



We thank Professor Filip Cools (AZ-VUB, Brussels) for his helpful comments on a previous version of this manuscript. We thank Mr. Luc Hourlay (KCE, Centre fédéral d’expertise des soins de santé, Brussels) for his assistance in the EMBASE search.

Authors’ Contributions

VR designed the study, analysed the data and wrote the initial draft of the manuscript. VR and CL performed the literature search. VR and IB evaluated the RCTs and extracted the data. All the authors interpreted the results and revised and approved the manuscript.

Compliance with ethical standards

Conflict of interest

VR has received speaker honoraria and sponsoring to attend a scientific meeting from Chiesi Belgium, a surfactant-producing company. The company was not involved in this study. CL and IB declare having no conflict of interest.

Financial support


Ethical approval

This article does not contain any study with human participants performed by any of the authors. All studies included in the meta-analysis were approved by ethical review boards and requested parental consent.

Supplementary material

431_2016_2789_MOESM1_ESM.pdf (225 kb)
Online Resource 1 Figure: Flow diagram for selection of eligible studies. (PDF 224 kb)
431_2016_2789_MOESM2_ESM.pdf (42 kb)
Online Resource 2 Table: Risk of bias assessment. (PDF 41 kb)
431_2016_2789_MOESM3_ESM.pdf (318 kb)
Online Resource 3 Figure: Forest plots for each dichotomous outcomes. (PDF 318 kb)
431_2016_2789_MOESM4_ESM.pdf (125 kb)
Online Resource 4 Figure: Forest plots for infants born below 29 weeks. (PDF 124 kb)
431_2016_2789_MOESM5_ESM.pdf (56 kb)
Online Resource 5 Table: Data for continuous outcomes. (PDF 55 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  1. 1.Neonatology divisionCHU de Liège, University of Liège, and CHR CitadelleLiègeBelgium

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