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This review found that heated, humidified high-flow oxygen therapy by nose was a safe and effective alternative to other non-invasive methods for supporting breathing for preterm babies. It was less likely to cause nasal injury compared with other methods that used nose tubes. Oxygen therapy is commonly used as a form of breathing support for preterm babies with respiratory distress syndrome, a common complication of premature delivery that makes it hard for a baby to breathe. High-flow therapy may therefore be used instead of mechanical ventilation for some babies or after mechanical ventilation, though it is still uncertain as to whether the therapies are equivalent. Data remains scarce for very preterm infants (less than 28 weeks gestational age) and so high-flow therapy is not for them until further research is completed.

Why was this study needed?

Preterm babies often have underdeveloped lungs which are stiff and don’t carry oxygen efficiently into the blood. Mechanical ventilation has traditionally been used to support the baby’s breathing by blowing air directly into the lungs via a tube into the airway. This form of ventilation, even with great care, can risk damaging the baby’s lungs or airway. Efforts are made either to avoid mechanical ventilation or to shorten the time for which it is needed by using alternative means of support for breathing.

In Europe in 2010, 92% of babies born at 24–25 weeks’ gestation had respiratory distress syndrome and needed some form of ventilation. This fell to 88% at 26–27 weeks, 76% at 28–29 weeks and 57% at 30–31 weeks. When managed with early non-invasive ventilation, babies of 26–29 weeks can be managed without intubation or surfactant about half the time.

The usual non-invasive respiratory support has hitherto been nasal continuous positive airway pressure. Heated, humidified high-flow cannula therapy has become a commonly used alternative in recent years but the evidence supporting its efficacy and safety has not yet been established. This review compared high-flow therapy with other non-invasive ventilation techniques in preterm infants.

What did this study do?

This was a systematic review with meta-analysis of nine randomised controlled trials in preterm infants that compared high-flow therapy with other modes of non-invasive ventilation. Preterm infants were described as being less than 37 weeks’ gestational age at birth. Eight of the nine studies compared high-flow therapy with nasal continuous positive airway pressure.

The review followed reliable systematic review methodology and most of the trials had an overall low risk of bias.

What did it find?

  • There was no difference in failure rate when used as the primary mode of respiratory support. High flow therapy failed 17% of the time compared with 16% of the time with other non-invasive ventilators (odds ratio [OR] 1.02, 95% confidence interval [CI] 0.55 to 1.88). Failure was defined differently across trials, but most definitions included the observation of vital signs such as body temperature, blood pressure, heart rate and breathing rate. Failure resulted in either transferring the baby to a mechanical ventilator or alternative non-invasive ventilation. This result was from a meta-analysis of four trials.
  • There was also no difference in failure rate when used after removal from a mechanical ventilator. High-flow therapy failed 24% of the time compared to 21% of the time with other non-invasive methods (OR 1.09, 95% CI 0.58 to 2.02). This result was from a meta-analysis of three trials.
  • There were no significant differences in mortality between the groups.
  • Preterm infants on high-flow therapy had a third of the instances of nasal injury compared to other forms of non-invasive ventilation. Nasal injury occurred in fewer babies on humidified, heated high flow therapy, than on other modes of non-invasive ventilation using nasal cannula.

What does current guidance say on this issue?

The European Consensus Guidelines 2013 state that respiratory support in the form of mechanical ventilation may be lifesaving but can cause lung injury. Protocols should be directed at avoiding mechanical ventilation where possible by using non-invasive respiratory support. Humidified, heated high flow therapy should be properly evaluated compared to nasal continuous positive airway pressure before firm recommendations can be made.

A guideline in development from NICE on preterm labour and birth is expected to be published in November 2015.

What are the implications?

High-flow therapy was similar in efficacy and safety compared to other conventional modes of non-invasive ventilation in preterm infants, and less likely to cause nasal injury. The underlying trials were small and none, on their own, showed a statistically significant effect. They showed very different results with a lack of consistency in the direction of effect. It may be too soon to say confidently that these types of treatment are equivalent and so further data may still be required to help decision makers.

Note that only two of the included studies included infants born at less than 32 weeks’ gestational age and data remain scarce for extreme preterm infants born less than 28 weeks’ gestational age. Until further research is done, high flow therapy is therefore not recommended in extremely preterm infants.


Kotecha SJ, Adappa R, Gupta N, et al. Safety and Efficacy of High-Flow Nasal Cannula Therapy in Preterm Infants: A Meta-analysis. Pediatrics. 2015;136(3):542-53.


NHS Choices. Neonatal respiratory distress syndrome. London: NHS Choices; 2015.

Sweet DG, Carnielli V, Greisen G, et al; European Association of Perinatal Medicine. European consensus guidelines on the management of neonatal respiratory distress syndrome in preterm infants - 2013 update. Neonatology. 2013;103(4):353-68.

Wilkinson D, Andersen C, O'Donnell CP, De Paoli AG. High flow nasal cannula for respiratory support in preterm infants. Cochrane Database Syst Rev. 2011;(5):CD006405.

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


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Neonatal respiratory distress syndrome is a common reason for babies needing support for breathing. The underlying cause is the lack of surfactant in the lungs. Surfactant is made up of proteins and fats, helps keep the lungs inflated and prevents the lung’s air sacs collapsing.

A baby normally begins producing surfactant sometime between weeks 24 and 28 of pregnancy. Most babies produce enough surfactant to breathe normally by week 34. Premature babies may not have enough surfactant in their lungs. These babies often require respiratory support by either mechanical ventilation or non-invasive ventilation.


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