Article Text

Download PDFPDF
Late surfactant administration after 48 hours of age in preterm neonates with respiratory insufficiency: a systematic review and meta-analysis
  1. Gonzalo Solís-García1,2,
  2. Sara Elias1,
  3. Michael Dunn3,
  4. Bonny Jasani1
  1. 1 Neonatology, The Hospital for Sick Children, Toronto, Ontario, Canada
  2. 2 Neonatology, Hospital Universitario Doce de Octubre, Madrid, Spain
  3. 3 Neonatology, Sunnybrook Health Sciences Center, Toronto, Ontario, Canada
  1. Correspondence to Dr Gonzalo Solís-García, Neonatology, The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada; gonsolisg92{at}


Objective To systematically review and meta-analyse the effect of late surfactant administration versus placebo in reducing the incidence of death or bronchopulmonary dysplasia (BPD) in preterm infants.

Design PubMed, EMBASE, CINAHL and Cochrane CENTRAL were searched until 30 May 2023, for randomised controlled trials (RCTs) comparing administration of surfactant after 48 hours of age versus placebo in preterm ventilator-dependent neonates. The primary outcome was incidence of death or BPD at 36 weeks’ postmenstrual age (PMA). Secondary outcomes included incidence of BPD at 36 weeks PMA, pre-discharge mortality, use of postnatal steroids, post-discharge respiratory support, treatment with steroids or hospitalisation prior to 1-year corrected age.

Results Pooled analyses of four RCTs (N=850) showed no statistically significant difference between groups in the incidence of death or BPD at 36 weeks’ PMA (relative risk (RR) 0.99; 95% CI 0.90 to 1.10; Grades of Recommendation, Assessment, Development and Evaluation (GRADE): moderate). Late surfactant administration significantly decreased the need for post-discharge respiratory support prior to 1-year corrected age (two RCTs; N=522; RR 0.72; 95% CI 0.59 to 0.89; GRADE: low). Other secondary outcomes did not differ significantly between the groups.

Conclusions Administration of late surfactant does not improve the rates of death or BPD at 36 weeks when administered to preterm infants with prolonged respiratory insufficiency. Additional adequately powered trials are needed to establish the efficacy of late surfactant therapy in preterm infants.

PROSPERO registration number CRD42023432463.

  • Neonatology
  • Respiratory Medicine

Data availability statement

Data are available upon reasonable request.

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

Data availability statement

Data are available upon reasonable request.

View Full Text


  • X @gonsolisg

  • Contributors GS-G, BJ and SE designed the protocol for the study and collected the data. GS-G analysed the data and wrote the initial draft of the manuscript. BJ and MD critically reviewed and contributed significantly to the manuscript. GS-G, BJ and MD are guarantors and take full responsibility for the work.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

Linked Articles

  • Highlights from this issue
    Ben J Stenson