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Surfactant therapy in late preterm and term neonates with respiratory distress syndrome: a systematic review and meta-analysis
  1. Viraraghavan Vadakkencherry Ramaswamy1,
  2. Thangaraj Abiramalatha2,
  3. Tapas Bandyopadhyay3,
  4. Elaine Boyle4,
  5. Charles Christoph Roehr5,6,7
  1. 1 Department of Neonatology, Ankura Hospital for Women and Children, Hyderabad, Telangana, India
  2. 2 Department of Neonatology, Sri Ramachandra Institute of Higher Education and Research, Chennai, India
  3. 3 Department of Neonatology, Dr Ram Manohar Lohia Hospital and Post Graduate Institute of Medical Education and Research, New Delhi, Delhi, India
  4. 4 Department of Health Sciences, University of Leicester, Leicester, UK
  5. 5 Nuffield Department of Population Health, Medical Sciences Division, National Perinatal Epidemiology Unit, University of Oxford, Oxford, UK
  6. 6 Newborn Services, Southmead Hospital, North Bristol Trust, Bristol, UK
  7. 7 Faculty of Health Sciences, University of Bristol, Bristol, UK
  1. Correspondence to Dr Charles Christoph Roehr, Nuffield Department of Population Health, Medical Sciences, Division, University of Oxford, National Perinatal Epidemiology Unit, Oxford OX3 7LF, Oxfordshire, UK; ccroehr{at}


Background There are no evidence-based recommendations for surfactant use in late preterm (LPT) and term infants with respiratory distress syndrome (RDS).

Objective To investigate the safety and efficacy of surfactant in LPT and term infants with RDS.

Methods Systematic review, meta-analysis and evidence grading.

Interventions Surfactant therapy versus standard of care.

Main outcome measures Mortality and requirement for invasive mechanical ventilation (IMV).

Results Of the 7970 titles and abstracts screened, 17 studies (16 observational studies and 1 randomised controlled trial (RCT)) were included. Of the LPT and term neonates with RDS, 46% (95% CI 40% to 51%) were treated with surfactant. We found moderate certainty of evidence (CoE) from observational studies evaluating infants supported with non-invasive respiratory support (NRS) or IMV that surfactant use may be associated with a decreased risk of mortality (OR 0.45, 95% CI 0.32 to 0.64). Very low CoE from observational trials in which surfactant was administered at FiO2 >0.30–0.40 to infants on Continuous Positive Airway Pressure (CPAP) indicated that surfactant did not decrease the risk of IMV (OR 1.20, 95% CI 0.40 to 3.56). Very low to low CoE from the RCT and observational trials showed that surfactant use was associated with a significant decrease in risk of air leak, persistent pulmonary hypertension of the newborn (PPHN), duration of IMV, NRS and hospital stay.

Conclusions Current evidence base on surfactant therapy in LPT and term infants with RDS indicates a potentially decreased risk of mortality, air leak, PPHN and duration of respiratory support. In view of the low to very low CoE and widely varying thresholds for deciding on surfactant replacement in the included studies, further trials are needed.

  • neonatology
  • respiratory medicine

Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information.

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Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information.

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  • Contributors CCR, EB and VVR conceptualised the systematic review. TB, TA and VVR did acquisition, analysis and interpretation of data. CCR and EB provided further intellectual input and revised the first draft. All authors approved the final version submitted for publication and agree to be accountable for all aspects of the work. VVR is the guarantor for this manuscript.

  • 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.

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