Cheng et al. BMC Pediatrics(2024) 24:514
https://doi.org/10.1186/s12887-024-04981-y

BMC Pediatrics

RESEARCH

Open Access

Non-invasive neurally adjusted ventilatory
assist (NIV-NAVA) in the neonatal intensive
care unit (NICU): an Australian NICU
experience
Jonathan Cheng1,2, Trisha Parmar3, John Smyth1,3, Srivinas Bolisetty1,3, Kei Lui1,3 and Tim Schindler1,3*
Abstract
Background Preterm infants often require non-invasive breathing support while their lungs and control ofrespiration are still developing. Non-invasive neurally adjusted ventilatory assist (NIV-NAVA) is an emerging technologythat allows infants to breathe spontaneously while receiving support breaths proportional to their effort. This study
describes the first Australian Neonatal Intensive Care Unit (NICU) experience of NIV-NAVA.
Methods Retrospective cohort study of infants admitted to a major tertiary NICU between October 2017 and April
2021 supported with NIV-NAVA. Infants were divided into three groups based on the indication to initiate NIV-NAVA(post-extubation; apnoea; escalation). Successful application of NIV-NAVA was based on the need for re-intubation
within 48 h of application.
Results There were 169 NIV-NAVA episodes in 122 infants (82 post-extubation; 21 apnoea; 66 escalation). The median(range) gestational age at birth was 25 + 5 weeks (23 + 1 to 43 + 3 weeks) and median (range) birthweight was 963 g(365–4320 g). At NIV-NAVA application, mean (SD) age was 17 days (18.2), and median (range) weight was 850 g(501–4310 g). Infants did not require intubation within 48 h in 145/169 (85.2%) episodes [72/82 (87.8%) extubation;
21/21 (100%) apnoea; 52/66 (78.8%) escalation).
Conclusion NIV-NAVA was successfully integrated for the three main indications (escalation; post-extubation;
apnoea). Prospective clinical trials are still required to establish its effectiveness versus other modes of non-invasive
support.
Keywords Neurally adjusted ventilatory assist, Non-invasive ventilation, Ventilation weaning, Premature infant,Interactive ventilatory support*Correspondence:
Tim Schindler
tim.schindler@health.nsw.gov.au
1
University of New South Wales, Sydney, NSW 2032, Australia
2Westmead Hospital, Westmead, NSW 2145, Australia
3
Department of Newborn Care, Royal Hospital for Women, Barker St,
Randwick, NSW 2031, Australia© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0
International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you
give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified thelicensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images orother third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to thematerial. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation
or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://
creativecommons.org/licenses/by-nc-nd/4.0/.

Cheng et al. BMC Pediatrics(2024) 24:514

Background
Advancing medical knowledge and improving technology over the past decades has seen consistent increases
in survival rates for extreme preterm infants. Despite
these improvements, there continues to be high rates
of ventilator-associated complications with little reduction in rates of bronchopulmonary dysplasia (BPD). This
has resulted an increased use of non-invasive ventilation(NIV), including more sophisticated methods of achieving patient-triggered ventilation [1, 2]. Systems that synchronise respiratory effort with lung inflation may help
mitigate the long-term consequences of asynchrony
including lung injury via volutrauma or hyperoxia [3].
Consequently, the use of NIV continues to increase, however, there are a paucity of data demonstrating clinicalbenefit [2, 4].
Neonatal non-invasive ventilation is used for a variety
of indications which include respiratory failure, prevention of extubation failure and persistent, severe apnoea ofprematurity [4–7]. Well-established non-invasive modesof respiratory support range from nasal continuous positive airway pressure (NCPAP), nasal intermittent positive
pressure ventilation (NIPPV) and high-flow nasal cannula (HFNC). These all have varying volume and qualityof supporting literature [4–6, 8]. Indeed, NCPAP, NIPPVand HFNC have respective benefits with regard to safety,
efficacy, and ease of clinical use [1, 9]. However, there arelimitations to these modalities particularly in terms ofsynchrony with infants breathing efforts for NIPPV andinfants with absent or insufficient respiratory drive [4, 10,
11].
Neurally adjusted ventilatory assist (NAVA) differs from traditional ventilatory support, which adjusts
ventilation according to pressure or flow changes, as
NIV-NAVA delivers synchronised and scaled inspiratory support based upon the electrical diaphragmatic
signal (Edi) activity [12, 13]. Minute sensors are embedded within standard feeding tubes to detect Edi [3, 12,14]. This has no impact on feeding whilst monitoring
the overall respiratory drive [15]. A computer algorithm
analyses a filtered and amplified Edi signal to trigger
the ventilation system. The system detects the start of abreath as it is being initiated in the diaphragm and provides synchronised support during inspiration. The levelof support changes during inspiration in proportion to
the detected Edi [13, 14]. Inspiratory support discontinues as the system detects the Edi signal decreasing toallow expiration. With adequate support, neural feedback
mechanisms theoretically result in a decrease in respiratory drive with subsequent lower levels of inspiratory
support [15]. However, this is not always seen in preterm
infants due to immature neural feedback mechanisms[16].

Page 2 of 6

The aim of this study was to evaluate our experience
with NIV-NAVA by describing the intubation rate at 48 hfollowing the initiation of NIV-NAVA for the following
indications:• 	 Post-extubation as a weaning mode from invasive
ventilation.
• 	 As an escalation mode from NCPAP.
• 	 NCPAP therapy with a backup breath facility to treat
apnoeas.

Methods
This was a retrospective cohort study conducted at theRoyal Hospital for Women Neonatal Intensive Care Unit
(NICU). Infants admitted to this unit between 4 October
2017 and 20 April 2021 who received NIV-NAVA during their admission were included in the study. Standard
demographic maternal, perinatal, and neonatal data variables were extracted. Inclusion criteria included: inpatient, complete electronic medical records, indications
for NIV-NAVA applications including post-extubation,
escalation and apnoea (NIV-NAVA is not currently
used as a primary mode of respiratory support in thisunit). Exclusion criteria included: application of NIVNAVA at another hospital or for other indications and if
the patient had known congenital malformations of thelungs, airways or chest wall. All infants were managed
using the Royal Hospital for Women’s, “NAVA (Neurally
Adjusted Ventilatory Assist”, clinical guidelines (Appendix 1). Indications for the initiation of NIV-NAVA andtypical settings for these indications can be found in theclinical guidelines.
The primary outcome was the need for intubation
within 48 h of NIV-NAVA initiation. The decision for
intubation was at the discretion of the treating neonatologist. Infants were stratified by indication and analysed in subgroups. We also investigated change in FiO2
and PCO2 when NIV-NAVA was used as an escalation
mode. Infants may have required NIV-NAVA multiple
times and subsequently appear across multiple indicationgroups or record more than one episode for the same
indication.
The Respiratory Severity Score (RSS) was calculated
prior to initiation of NIV-NAVA to indicate level of respiratory illness upon study entry point. This was calculated
as either:
RSS (invasively ventilated inf ants)
P IP 2 × P EEP=+× F iO2%
3
3
ORCheng et al. BMC Pediatrics(2024) 24:514

RSS (non − invasively supported inf ants)
MAP=
× F iO2%P EEP
MAP, mean arterial pressure; PIP, Peak inspiratory pressure in cm; PEEP, Positive end-expiration pressure in cm
H2O; FiO2, fraction of inspired oxygen.
All statistical analyses were conducted using IBM
SPSS Statistics for Windows, Version 26.0 (IBM Corp.,
Armonk, NY: IBM Corp). Descriptive statistics were used
to present the results of the study and summarised to theindication for NIV-NAVA. Data was inspected for normality before further analysis. Continuous demographic
variables including the outcomes of FiO2 and pCO2 weresummarised by mean and standard deviation if normally
distributed and by median and range if not. Differences
between initial and subsequent FiO2 and pCO2 were analysed by a paired samples test across all three indications.
Statistical significance was set at p < 0.05.
The study was approved by the South Eastern Sydney
Local Health District (Northern Sector) Human Research
Ethics Committee (2020/ETH02488).

Results
122 infants were included in the study period; there were
169 episodes of NIV-NAVA use for the three different
indications. The average age of the infants commencing
NIV-NAVA therapy was 17.2 days with a median weightof 839 g. The median respiratory severity score was 2.6.
The perinatal clinical characteristics of included infants issummarised in Table 1.
Of the infants requiring extubation from invasive
ventilation, 72 (87.8%) did not require intubation after
48 h. 52 (78.8%) infants were successfully escalated from
NCPAP to NIV-NAVA. 21 (100%) of those requiring
NIV-NAVA for apnoea treatment were not intubated at
48 h. The overall rate of not requiring intubation following NIV-NAVA use was 145/169 (86%). There were 110
infants < 1000 g at the time of application of NIV-NAVA.
90/110 (82%) in this subgroup did not require intubation. The reason for intubation was not consistently
reported but was usually for oxygenation and/or ventilation failure. There were no significant changes in mean
FiO2 (33.8% before; 32.7% after [p = 0.353]) or pCO2 (49.4mmHg before; 48.8 mmHg after [p = 0.547]) with application of NIV-NAVA in the escalation group. The clinical characteristics of the infants whilst on NIV-NAVA in
addition to their prior ventilation modes is summarisedin Table 2. There were no adverse events documented
related to either the use of the NAVA catheter or the ventilation system.

Page 3 of 6

Discussion
This retrospective cohort study describes the first experience of NIV-NAVA in an Australian NICU and represents the largest reported cohort of NIV-NAVA infants[9, 10, 16–18]. Within 48 h of application of NIV-NAVA
for all indications, the majority of infants did not require
intubation (86%). This is encouraging as these infants
were at high risk of intubation, as evidenced by thecohort’s Respiratory Severity Scores (RSS) [19, 20]. The
particularly high rate of success in infants with apnoeas
highlights the effectiveness of the back-up support thatis activated when the system detects an apnoeic episode.
These results are consistent with other studies that haveshown low intubation rates following the application of
NIV-NAVA [21–27].
As a surrogate marker of respiratory status, we compared FiO2 and pCO2 before and after the application of
NIV-NAVA in the escalation group and found no significant differences. Previous similar studies have shown thatthe application of NIV-NAVA in this setting either has noeffect or improves these parameters [18, 22, 25, 28, 29].
The blood gases in this study were based on clinical need
and were not timed. As a result, there was significant
variability in the timing of FiO2 and pCO2 measurements
both before and after the application of NIV-NAVA as
well as the overall time between blood gases. In some circumstances, the two gases may not have been optimally
timed to accurately capture the change in respiratory status [30, 31].
There are a number of important limitations to
acknowledge in this study. Although it is reassuring thatthe rate of intubation in this cohort was low, there was
no way of determining how many of these infants would
have required intubation if alternative modes of noninvasive respiratory support were used. It was not possible to find a suitable control group of infants in whom
NIV-NAVA was not used as the infants in this cohort
were at significantly higher risk of needing intubationin which case their respiratory support was escalated
to NIV-NAVA. They were also not representative of atypical cohort of infants requiring non-invasive respiratory support. The study is also inherently limited by its
opportunistic nature, particularly with respect to finding objective measures of clinical change before and after
the application of NIV-NAVA. While it is reassuringthat infants in the escalation group had stable blood gas
parameters, the lack of control in the timing of blood collection limits what we can conclude.
NCPAP has a well-established, evidenced-based rolein the NICU environment and is the most widely used
non-invasive mode of support for infants with respiratory distress. However, there are clinical circumstanceswhere NCPAP alone does not provide adequate support
and other forms of NIPPV may not be synchronised.

Cheng et al. BMC Pediatrics(2024) 24:514

Page 4 of 6

Table 1 Perinatal clinical characteristics
Extubation(n = 62)
41 (62%)25 + 2 weeks(23 + 1 to 37 + 5)

Escalation(n = 55)
39 (67%)26 + 1 weeks(23 + 1 to 41 + 3)

Apnoeas(n = 18)
13 (65%)26 + 6 weeks(23 + 6 to 34 + 3)

Overall(n = 113)
78 (64%)25 + 5 weeks(23 + 1 to
43 + 3)708 (365–4310)
12 (18%)6 (9.1%)810 (365–3740)
9 (16%)
3 (5.2%)894 (498–2324)
1 (5.0%)1 (5.0%)963(365–4310)
18 (15%)8 (6.6%)53 (86%)8 (13%)
1 (1.6%)44 (80%)10 (18%)1 (1.8%)11 (65%)5 (28%)
1 (5.6%)

93/112* (83%)
18/112* (16%)
1/112* (0.9%)

45 (73%)5 (8.1%)
12 (19%)22 (36%)40 (73%)4 (7.3%)
11 (20%)18 (33%)19 (56%)
3 (17%)
5 (28%)
3/17* (18%)

78 (69%)23 (20%)12 (11%)
34/112* (30%)

15 (23%)10 (15%)3 (4.5%)38 (58%)12 (21%)6 (10%)
3 (5.2%)37 (64%)4 (20%)
0 (0.0%)1 (5.0%)15 (75%)30 (25%)14 (12%)5 (4.1%)73 (60%)5 (1–9)7 (1–9)6 (1–9)8 (4–10)5 (2–9)8 (4–9)5 (1–9)8 (1–10)

1/65* (1.5%)
27/65* (42%)
65 (99%)0 (0.0%)25 (43%)57 (98%)

1/19* (5.3%)
7/19* (37%)
19/19* (100%)

Surfactant, number receiving surfactant (%)
Caffeine use, number who received caffeine (%)

63 (95%)59 (89%)55 (95%)50/57* (88%)

19 (95%)
19/20* (95%)

Intraventricular haemorrhage (IVH)
All IVH (%)
Major IVH (Grade 3/4) (%)
Necrotising enterocolitis (NEC) (%)
Postnatal steroids (%)
Bronchopulmonary dysplasia (BPD) (%)
Retinopathy of prematurity (ROP) requiring laser or intra-vitreal injection(%)
Survival (%)

18 (27%)7 (10.6%)

8 (14%)
3 (5.2%)

2/17* (12%)
1/17* (5.9%)

2/120* (1.7%)
48/120* (40%)
119/121*(98%)
115 (94%)
109/121*(90%)
25/119* (21%)
11/119* (9.2%)

7/65* (11%)
48 (73%)49 (74%)10 (15%)

4/57* (7.0%)
31 (53%)43 (74%)6 (10%)

1/17* (5.9%)
8 (44%)
12 (60%)
1/18* (5.6%)

11/117* (9.4%)
71 (59%)88 (72%)
15/120* (13%)

61 (92%)54 (93%)20 (100%)

113 (93%)

Male sex (%)
Gestational age, median age in weeks and days (minimum-maximum)

Birthweight (BW)Median BW in grams (minimum-maximum)
BW number < 10th percentile (%)
BW < 3rd percentile (%)
Plurality
Singleton (%)
Twins (%)
Triplets (%)
Antenatal steroids
Complete (%)
Incomplete (%)
Nil (%)
Chorioamnionitis (%)
Delivery mode
Normal vaginal
Breech vaginalInstrumental vaginal
Lower segment caesarean section
Apgar score
Median Apgar 1 min (minimum-maximum)Median Apgar 5 min (minimum-maximum)
Sepsis
Early onset sepsis (%)
Late onset sepsis (%)
Respiratory distress syndrome (RDS) (%)*Incomplete data
List of Abbreviations
BW, birthweight; RDS, respiratory distress syndrome; IVH, intraventricular haemorrhage; NEC, necrotising enterocolitis; BPD, bronchopulmonary dysplasia; ROP, retinopathy ofprematurity

NIV-NAVA has the theoretical advantages of optimisingsynchrony with breathing and providing support that is
proportional to infants’ breathing efforts. Cohort studies such as this continue to show the stability that can beachieved with the application of NIV-NAVA in high-risk
infants and adds to the growing body of evidence that
supports its use in the NICU environment in selectedclinical circumstances. Large, high-quality randomised
trials are currently lacking but are essential to help further establish where NIV-NAVA fits into clinical practice[12, 32].
This study has shown that NIV-NAVA can be successfully integrated into the NICU environment for threemain indications (escalation; post-extubation; apnoea).

Cheng et al. BMC Pediatrics(2024) 24:514

Page 5 of 6

Table 2 NIV-NAVA clinical characteristics

Age when on NIV-NAVA, age in days (SD)
Corrected gestational age on NIV-NAVA, median corrected gestational age inweeks and days (minimum-maximum)
Weight when on NIV-NAVA, median weight in grams (minimum-maximum)
Previous Ventilation
Conventional ventilation (%)
NCPAP (%)
High flow (%)
HFOV (%)
Respiratory Severity Score (RSS)**, median RSS (minimum-maximum)
Intubation not required within 48 h of initiation of NIV-NAVA (%)
Weight on NAVA ≤ 1000 g

Extubation(n = 82)
18.8 (19.2)
27 + 5 weeks(23 + 6 to 42 + 0)

Escalation(n = 66)
17.3 (18.8)
28 + 3 weeks(25 + 3 to 44 + 4)827
(490–4310)

901(575–3740)

Apnoeas (n = 21) Overall(n = 169)
10.4 (9.6)
17.2 (18.2)
28 + 0 weeks
28 + 1 weeks(24 + 6 to 34 + 3) (23 + 6 to
44 + 4)847
839(575–2350)(490–4310)

80 (98%)N/A
N/A
2 (2.4%)2.8(1.72–6.90)
72/82 (88%)
48/58 (83%)

N/A
65 (99%)1 (1.5%)N/A
2.5(0.8-7.0)
52/66 (79%)
30/40 (75%)

N/A
20 (95%)1 (4.8%)N/A
1.8(1.3–3.2)
21/21 (100%)
12/12 (100%)

80 (47%)85 (50%)2 (1.2%)2 (1.2%)2.6(0.8-7.0)
145/169 (86%)
90/110 (82%)**Calculated by RSS = MAP/PEEP x FiO2% or (PIP/3 + PEEPx2/3) x FiO2%
List of Abbreviations
NIV-NAVA, non-invasive neurally adjusted ventilatory assist; SD, standard deviation; NCPAP, nasal continuous positive airway pressure; HFOV, high frequency oscillatory ventilation;
RSS, Respiratory Severity Score; MAP, mean arterial pressure; PEEP, Positive end-expiration pressure; FiO2, fraction of inspired oxygen; PIP, Peak inspiratory pressure; Rate, rate inbreaths per minute; Ti, total inspiratory time in seconds;

Although promising, it is important to note that prospective clinical trials are still required to establish the effectiveness of NIV-NAVA by comparing it to other modes of
non-invasive support.

Supplementary Information

The online version contains supplementary material available at https://doi.
org/10.1186/s12887-024-04981-y.

study, being a retrospective study of de-identified data. All data was handled
as per the New South Wales Information Privacy Commission Statutory
Guidelines for Research and the study was conducted in accordance withapplicable Privacy Acts and Regulations.
Consent for publication
Not applicable.
Competing interests
The authors declare no competing interests.
Received: 15 May 2024 / Accepted: 29 July 2024

Supplementary Material 1
Acknowledgements
We acknowledge Dr Kylie-Ann Mallit for her support and expertise withstatistical analysis. We also acknowledge the Bidjigal and Gadigal Peoples of
the Eora Nation, whose land on which this research was conducted.
Author contributions
TS developed the original concept for the study. TP, JS, SB, and KL provided
important intellectual input into the development of the study protocol.
TS and TP performed a preliminary analysis to establish feasibility. JC was
responsible for all data collection. JC performed statistical analysis with theassistance of Dr Kylie-Ann Mallit (acknowledgements). JC drafted the initialmanuscript and all authors provided editorial input and approved the final
manuscript.
Funding
This research was investigator-initiated and did not require external funding.
Data availability
The datasets used and analysed during the study are available from thecorresponding author (Dr Tim Schindler) on reasonable request.

Declarations
Ethics approval and consent to participate
The study was approved by the South Eastern Sydney Local Health District(Northern Sector) Human Research Ethics Committee (2020/ETH02488) who
deemed that individual consent was not required due to the nature of theReferences
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