Nasal high flow therapy for breathing support in preterm babies

Review question

In preterm babies, what are the benefits and harms of nasal high flow therapy (high flow) when used for breathing support soon after birth, compared with other types of non-invasive breathing support?

What is respiratory support and how is it treated?

Preterm infants (born before their due date) often require support with their breathing soon after birth. Non-invasive respiratory support is provided without placing a breathing tube in the baby's windpipe. There are several types of non-invasive respiratory support. High flow is one type that delivers warm air and oxygen via two small prongs that sit inside the infant's nostrils. Alternatives to high flow include continuous positive airway pressure (CPAP), where continuous pressure (rather than flow) of oxygen is given via larger prongs or a mask, and nasal intermittent positive pressure ventilation (NIPPV) where, in addition to CPAP, inflations of oxygen at a higher pressure are occasionally given.

What did we do?

We searched medical databases for well-designed studies evaluating the benefits and harms of high flow respiratory support in preterm infants compared to other forms of non-invasive respiratory support.

What did we find?

We found 13 studies including 2540 preterm babies that compared high flow with other non-invasive ways of supporting babies' breathing soon after birth. There are nine studies awaiting classification and 13 ongoing studies. The included studies differed in the treatments they compared, the flows of oxygen used, whether CPAP could be used if high flow did not work and the approach to the use of surfactant (a medication used to help prevent the small airways collapsing down) in babies with more severe breathing difficulties.

What did we find?

When used soon after birth in preterm babies, high flow may make little to no difference to death or bronchopulmonary dysplasia (a chronic lung disease in preterm babies) compared with CPAP or NIPPV. High flow probably increases treatment failure compared with CPAP. For example, babies treated with high flow might have needed higher oxygen concentrations or had worse blood test results. CPAP worked better than high flow in around 10 more babies out of every 100. However, high flow probably makes little to no difference to the likelihood of needing intubation (placement of a breathing tube). High flow probably caused less damage to the infant's nose, compared with CPAP or NIPPV and probably reduced the risk of pneumothorax (air in the space between the lung and the chest wall). There were very few extremely preterm infants (born before 28 weeks' gestation) included in these studies. Therefore, we remain unsure about the benefits and harms of high flow soon after birth for extremely preterm infants.

What are the limitations of the evidence?

Overall, we have very low to moderate confidence in these findings. Our confidence is limited because clinicians in the studies knew which treatment babies received; the results varied widely as some studies showed benefit with one type of breathing support while other studies showed benefit with the comparator type of breathing support; and there were low numbers of events for some outcomes making it difficult to compare groups.

How up to date is this evidence?

The search is up to date as of 12 March 2022.

Authors' conclusions: 

The use of nHF for primary respiratory support in preterm infants of 28 weeks' gestation or greater may result in little to no difference in death or BPD, compared with CPAP or NIPPV. nHF likely results in an increase in treatment failure within 72 hours of trial entry compared with CPAP; however, it likely does not increase the rate of mechanical ventilation. Compared with CPAP, nHF use likely results in less nasal trauma and likely a reduction in pneumothorax. As few extremely preterm infants less than 28 weeks' gestation were enrolled in the included trials, evidence is lacking for the use of nHF for primary respiratory support in this population.

Read the full abstract...
Background: 

Nasal high flow (nHF) therapy provides heated, humidified air and oxygen via two small nasal prongs, at gas flows of more than 1 litre/minute (L/min), typically 2 L/min to 8 L/min. nHF is commonly used for non-invasive respiratory support in preterm neonates. It may be used in this population for primary respiratory support (avoiding, or prior to the use of mechanical ventilation via an endotracheal tube) for prophylaxis or treatment of respiratory distress syndrome (RDS). This is an update of a review first published in 2011 and updated in 2016.

Objectives: 

To evaluate the benefits and harms of nHF for primary respiratory support in preterm infants compared to other forms of non-invasive respiratory support.

Search strategy: 

We used standard, extensive Cochrane search methods. The latest search date March 2022.

Selection criteria: 

We included randomised or quasi-randomised trials comparing nHF with other forms of non-invasive respiratory support for preterm infants born less than 37 weeks' gestation with respiratory distress soon after birth.

Data collection and analysis: 

We used standard Cochrane Neonatal methods. Our primary outcomes were 1. death (before hospital discharge) or bronchopulmonary dysplasia (BPD), 2. death (before hospital discharge), 3. BPD, 4. treatment failure within 72 hours of trial entry and 5. mechanical ventilation via an endotracheal tube within 72 hours of trial entry. Our secondary outcomes were 6. respiratory support, 7. complications and 8. neurosensory outcomes. We used GRADE to assess the certainty of evidence.

Main results: 

We included 13 studies (2540 infants) in this updated review. There are nine studies awaiting classification and 13 ongoing studies. The included studies differed in the comparator treatment (continuous positive airway pressure (CPAP) or nasal intermittent positive pressure ventilation (NIPPV)), the devices for delivering nHF and the gas flows used. Some studies allowed the use of 'rescue' CPAP in the event of nHF treatment failure, prior to any mechanical ventilation, and some allowed surfactant administration via the INSURE (INtubation, SURfactant, Extubation) technique without this being deemed treatment failure. The studies included very few extremely preterm infants less than 28 weeks' gestation. Several studies had unclear or high risk of bias in one or more domains.

Nasal high flow compared with continuous positive airway pressure for primary respiratory support in preterm infants

Eleven studies compared nHF with CPAP for primary respiratory support in preterm infants. When compared with CPAP, nHF may result in little to no difference in the combined outcome of death or BPD (risk ratio (RR) 1.09, 95% confidence interval (CI) 0.74 to 1.60; risk difference (RD) 0, 95% CI −0.02 to 0.02; 7 studies, 1830 infants; low-certainty evidence). Compared with CPAP, nHF may result in little to no difference in the risk of death (RR 0.78, 95% CI 0.44 to 1.39; 9 studies, 2009 infants; low-certainty evidence), or BPD (RR 1.14, 95% CI 0.74 to 1.76; 8 studies, 1917 infants; low-certainty evidence). nHF likely results in an increase in treatment failure within 72 hours of trial entry (RR 1.70, 95% CI 1.41 to 2.06; RD 0.09, 95% CI 0.06 to 0.12; number needed to treat for an additional harmful outcome (NNTH) 11, 95% CI 8 to 17; 9 studies, 2042 infants; moderate-certainty evidence). However, nHF likely does not increase the rate of mechanical ventilation (RR 1.04, 95% CI 0.82 to 1.31; 9 studies, 2042 infants; moderate-certainty evidence). nHF likely results in a reduction in pneumothorax (RR 0.66, 95% CI 0.40 to 1.08; 10 studies, 2094 infants; moderate-certainty evidence) and nasal trauma (RR 0.49, 95% CI 0.36 to 0.68; RD −0.06, 95% CI −0.09 to −0.04; 7 studies, 1595 infants; moderate-certainty evidence).

Nasal high flow compared with nasal intermittent positive pressure ventilation for primary respiratory support in preterm infants

Four studies compared nHF with NIPPV for primary respiratory support in preterm infants. When compared with NIPPV, nHF may result in little to no difference in the combined outcome of death or BPD, but the evidence is very uncertain (RR 0.64, 95% CI 0.30 to 1.37; RD −0.05, 95% CI −0.14 to 0.04; 2 studies, 182 infants; very low-certainty evidence). nHF may result in little to no difference in the risk of death (RR 0.78, 95% CI 0.36 to 1.69; RD −0.02, 95% CI −0.10 to 0.05; 3 studies, 254 infants; low-certainty evidence). nHF likely results in little to no difference in the incidence of treatment failure within 72 hours of trial entry compared with NIPPV (RR 1.27, 95% CI 0.90 to 1.79; 4 studies, 343 infants; moderate-certainty evidence), or mechanical ventilation within 72 hours of trial entry (RR 0.91, 95% CI 0.62 to 1.33; 4 studies, 343 infants; moderate-certainty evidence). nHF likely results in a reduction in nasal trauma, compared with NIPPV (RR 0.21, 95% CI 0.09 to 0.47; RD −0.17, 95% CI −0.24 to −0.10; 3 studies, 272 infants; moderate-certainty evidence). nHF likely results in little to no difference in the rate of pneumothorax (RR 0.78, 95% CI 0.40 to 1.53; 4 studies, 344 infants; moderate-certainty evidence).

Nasal high flow compared with ambient oxygen

We found no studies examining this comparison.

Nasal high flow compared with low flow nasal cannulae

We found no studies examining this comparison.