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This is a plain English summary of an original research article. The views expressed are those of the author(s) and reviewer(s) at the time of publication.

This systematic review found high-flow oxygen delivered by nose was as effective and safe as other non-invasive methods of breathing support for preterm babies. The numbers of treatment failures, deaths and rates of chronic lung disease were similar.

Most studies were of high-flow oxygen for babies after tubes used for ventilation had been removed. For these babies use of high-flow techniques were less likely to cause nasal damage or a collapsed lung than other non-invasive methods.

High-flow oxygen therapy delivers gas through thin tubes that sit just inside each nostril, whereas the most common non-invasive alternative - continuous positive airway pressure –usually delivers gas through tight fitting nasal prongs. Both carry risk of damaging the nose.

The review analysed 15 trials that were open to bias due to potential selective reporting of outcomes.

It was not possible to say which non-invasive option was best, so the benefits and limitations of different approaches should be weighed up on a case by case basis.

Why was this study needed?

About eight out of every 100 babies born in the UK are born prematurely and many need help to breathe because of underdeveloped lungs.

Mechanical ventilation has traditionally been used to support the baby’s breathing by blowing air directly into the lungs via a tube in the airway. It is available in hospitals where babies are delivered, but even with great care, it risks damaging the baby’s lungs or airway.

So efforts are made either to avoid mechanical ventilation, or to shorten the time it is needed by using other less-invasive methods, once mechanical ventilation tubes are removed.

Nasal continuous positive airway pressure is a common and effective non-invasive breathing support option. High-flow nasal cannula therapy has been adopted in recent years with the perceived advantage of being less risky or invasive and simpler to administer. The efficacy and safety evidence for high-flow therapy is still uncertain, despite its widespread use in neonatal practice and this study set out to try clarify the issue.

This review aimed to find out how high-flow therapy compared with other non-invasive forms of breathing support in preterm babies by combining the results of several trials. It updates a similar 2011 systematic review that concluded there was insufficient evidence to establish the effectiveness or safety of high flow therapy, having identified just four relevant trials.

A previous 2015 NIHR Signal looked at heated, humidified high-flow oxygen to support breathing in preterm babies, one way of delivering this therapy. The review underlying this identified nine trials.

What did this study do?

This Cochrane review found 15 randomised trials comparing high flow therapy with other non-invasive breathing support methods in 1,730 preterm babies (before 37 weeks of pregnancy).

It mainly compared high-flow therapy with nasal continuous positive airway pressure (CPAP) and nasal intermittent positive pressure ventilation. Researchers identified one trial of humidified versus non-humidified high flow therapy.

Breathing support occurred immediately after birth, or following the removal of a breathing tube (extubation) already in place as part of mechanical breathing support.

Trials were rarely registered and so were open to bias due to potential selective reporting of outcomes. This lessens the chance high-flow therapy will be shown to be worse than alternatives.

What did it find?

  • Deaths were rare, but after high flow nasal oxygen use, the rate was similar to the death rate using CPAP. For example, in six trials including 934 babies treated with high flow oxygen, the risk of deaths in babies that were intubated first and then given oxygen after extubation was statistically no different whichever method was used, the typical RR was 0.77, (95% CI 0.43 to 1.36).
  • There were also no significant differences in rates chronic lung disease, treatment failure (see Definitions) or re-intubation between high flow therapy and the other non-invasive techniques tested (six trials, 934 babies).
  • Only one trial (75 babies) compared high flow therapy with nasal intermittent positive pressure ventilation shortly after birth, and also found no difference.
  • For babies who were stable on CPAP, two trials (149 babies) found those who switched to high flow therapy spent around three days less time in hospital compared with those who remained on CPAP. The effect of high flow therapy on duration of breathing in this scenario was not clear; one trial showed high flow therapy increased the duration of breathing support, the other trial showed the opposite.
  • Compared with nasal CPAP, babies using high flow therapy had less damage to their nose (four trials, 645 babies).

What does current guidance say on this issue?

NICE guidance on Preterm labour and birth (2015) does not give specific recommendations on breathing support in newborns.

What are the implications?

The newer high-flow therapy was similar in efficacy and safety compared with more established non-invasive alternatives for breathing support in the preterm babies, with a lower chance of nasal injury.

The trials were small and many were likely to be affected by bias; meaning we don’t know if some of the lack of differences observed were real, or due to study biases.

The effectiveness of high-flow therapy in very preterm (less than 28 weeks gestational age) or late preterm infants (more than 32 weeks) was not addressed, due to trials in these groups.


Citation and Funding

Wilkinson D, Andersen C, O'Donnell CPF et al. High flow nasal cannula for respiratory support in preterm infants. Cochrane Database Syst Rev. 2016;(2):CD006405.

This review was funded by the University of Oxford, Adelaide and Melbourne, as well as NHMRC (Australia) and US Department of Health and Human Services.



NHS Choices. Premature labour and birth. Signs of premature labour. London: Department of Health; last reviewed 2015.

NICE. Preterm labour and birth. NG25. London: National Institute for Health and Care Excellence; 2015.

NIHR DC. Heated, humidified high-flow oxygen therapy may be a useful alternative to other forms of respiratory support for preterm babies. Southampton: National Institute for Health Research Dissemination Centre; 2015.

Produced by the University of Southampton and Bazian on behalf of NIHR through the NIHR Dissemination Centre

NIHR Evidence is covered by the creative commons, CC-BY licence. Written content may be freely reproduced provided that suitable acknowledgement is made. Note, this license excludes comments made by third parties, audiovisual content, and linked content on other websites.

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Treatment failure was variably defined across the 15 trials but usually included the need to insert a breathing tube into the baby’s windpipe (intubation) based on different medical needs such as:

  • temporary pauses in breathing (apnoea)
  • respiratory distress (rapid, shallow breathing, blue lips and extremities)
  • breathing failure leading to a build-up of carbon dioxide in the blood (respiratory acidosis)
  • sustained need for oxygen (showing high-flow nasal cannula therapy wasn’t working)

Other criteria of treatment failure included the use of rescue treatment following HFNC, such as continuous positive airway pressure or nasal intermittent positive pressure ventilation without subsequent intubation. Some trials didn’t give definitions of treatment failure.

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