Diaphragm-triggered non-invasive respiratory support for preventing respiratory failure in preterm infants

Review question

In preterm infants, does diaphragm-triggered non-invasive respiratory support compared with other modes of non-invasive respiratory support prevent respiratory failure?


Diaphragm-triggered non-invasive respiratory support uses the electrical signal from the breathing muscles to guide when an infant is trying to breathe. This gives infants support that is both timed with their breathing efforts and in proportion to how hard they are working to breathe. It has the potential to help infants avoid invasive breathing support with a breathing tube. It is currently unclear whether there is a beneficial effect on outcomes for preterm infants.

Study characteristics

We found 15 studies that assessed the effect of diaphragm-triggered non-invasive respiratory support in infants through searches of medical databases up to 10 May 2019. Of these 15, two studies (involving a total of 23 preterm infants) were eligible for inclusion in the review. Ten studies were either awaiting publication or are ongoing.

Key results

There is limited data from randomised controlled trials to determine the effect of diaphragm-triggered non-invasive respiratory support on important outcomes. We were able to include only two small randomised controlled trials in the review. Both studies involved infants switching from one type of support to the other and were focused on short-term changes in breathing patterns.

Quality of evidence

We were not able to make any meaningful conclusions in this review due to limited data and very low quality evidence. Large, high-quality studies are needed to determine whether diaphragm-triggered non-invasive respiratory support can prevent respiratory failure.

Authors' conclusions: 

Due to limited data and very low certainty evidence, we were unable to determine if diaphragm-triggered non-invasive respiratory support is effective or safe in preventing respiratory failure in preterm infants. Large, adequately powered randomised controlled trials are needed to determine if diaphragm-triggered non-invasive respiratory support in preterm infants is effective or safe.

Read the full abstract...

Diaphragm-triggered non-invasive respiratory support, commonly referred to as NIV-NAVA (non-invasive neurally adjusted ventilatory assist), uses the electrical activity of the crural diaphragm to trigger the start and end of a breath. It provides variable inspiratory pressure that is proportional to an infant's changing inspiratory effort. NIV-NAVA has the potential to provide effective, non-invasive, synchronised, multilevel support and may reduce the need for invasive ventilation; however, its effects on short- and long-term outcomes, especially in the preterm infant, are unclear.


To assess the effectiveness and safety of diaphragm-triggered non-invasive respiratory support in preterm infants (< 37 weeks' gestation) when compared to other non-invasive modes of respiratory support (nasal intermittent positive pressure ventilation (NIPPV); nasal continuous positive airway pressure (nCPAP); high-flow nasal cannulae (HFNC)), and to assess preterm infants with birth weight less than 1000 grams or less than 28 weeks' corrected gestation at the time of intervention as a sub-group.

Search strategy: 

We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2019, Issue 5), MEDLINE via PubMed (1946 to 10 May 2019), Embase (1947 to 10 May 2019), and CINAHL (1982 to 10 May 2019). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi-randomised trials.

Selection criteria: 

Randomised and quasi-randomised controlled trials that compared diaphragm-triggered non-invasive versus other non-invasive respiratory support in preterm infants.

Data collection and analysis: 

Two review authors independently selected trials, assessed trial quality and extracted data from included studies. We performed fixed-effect analyses and expressed treatment effects as mean difference (MD), risk ratio (RR), and risk difference (RD) with 95% confidence intervals (CIs). We used the generic inverse variance method to analyse specific outcomes for cross-over trials. We used the GRADE approach to assess the certainty of evidence.

Main results: 

There were two small randomised controlled trials including a total of 23 infants eligible for inclusion in the review. Only one trial involving 16 infants included in the analysis reported on either of the primary outcomes of the review. This found no difference in failure of modality between NIV-NAVA and NIPPV (RR 0.33, 95% CI 0.02 to 7.14; RD −0.13, 95% CI -0.41 to 0.16; 1 study, 16 infants; heterogeneity not applicable).

Both trials reported on secondary outcomes of the review, specific for cross-over trials (total 22 infants; 1 excluded due to failure of initial modality). One study involving seven infants reported a significant reduction in maximum FiO₂ with NIV-NAVA compared to NIPPV (MD −4.29, 95% CI −5.47 to −3.11; heterogeneity not applicable). There was no difference in maximum electric activity of the diaphragm (Edi) signal between modalities (MD −1.75, 95% CI −3.75 to 0.26; I² = 0%) and a significant increase in respiratory rate with NIV-NAVA compared to NIPPV (MD 7.22, 95% CI 0.21 to 14.22; I² = 72%) on a meta-analysis of two studies involving a total of 22 infants. The included studies did not report on other outcomes of interest.