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Comparison of heated humidified high-flow nasal cannula versus nasal continuous positive airway pressure as a primary mode of respiratory support for respiratory distress in newborns: A tertiary care-based study from Western India
*Corresponding author: Sayan Kumar Das, Department of Paediatrics, Gujarat Medical Education and Research Society (GMERS) Medical College, Gandhinagar, Gujarat, India. dreamysayan@gmail.com
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Received: ,
Accepted: ,
How to cite this article: Gwalani M, Das SK, Dalal E. Comparison of heated humidified high-flow nasal cannula versus nasal continuous positive airway pressure as a primary mode of respiratory support for respiratory distress in newborns: A tertiary care-based study from Western India. Karnataka Paediatr J. doi: 10.25259/KPJ_21_2026
Abstract
Objectives:
One of the main causes of newborn morbidity and mortality is respiratory distress (RD) syndrome. Although it is frequently used for non-invasive assistance, nasal continuous positive airway pressure (NCPAP) can result in nasal damage and poor tolerability. Although there is little comparative data, the heated humidified high-flow nasal cannula (HHHFNC) is a kinder substitute. The objective of the study is to evaluate the results of newborns with RD treated with NCPAP as the primary support against HHHFNC.
Material and Methods:
In a prospective interventional research, 101 newborns were assigned to either NCPAP (n = 50) or HHHFNC (n = 51) within 12 h of birth. Mortality, complications, time to full feeds, ventilator demand, baseline features, and respiratory support duration were documented.
Results:
Groups were comparable in gestation, birth weight, and distress severity. Overall ventilator need and mortality were similar (high-flow nasal cannula [HFNC] 25.5% vs. NCPAP 40%; p = 0.149; mortality 7.8% vs. 8%; p = 1.0). Term infants on HFNC needed significantly less ventilator support (20% vs. 55.6%; p = 0.03). HFNC was associated with lower nasal trauma (0% vs. 8%; p = 0.04) and faster achievement of full feeds (3.98 vs. 4.82 days; p = 0.04).
Conclusion:
With the added advantages of less nasal trauma and faster enteral feeding, HHHFNC is just as effective as NCPAP for moderate paediatric RD. It is easy to use, safe, and well-tolerated.
Keywords
Heated humidified high-flow nasal cannula
Nasal continuous positive airway pressure
Neonates
Non-invasive ventilation
Respiratory distress syndrome
INTRODUCTION
Lung immaturity and surfactant deficiency are the main causes of respiratory distress syndrome (RDS), which is a major contributor to infant respiratory failure and mortality. In infants under 28 weeks and weighing <750 g, the incidence drops by 80% as gestational age and birth weight increase.[1]
Antenatal corticosteroids and early surfactant therapy have significantly minimised the incidence and seriousness of RDS. Increased awareness has also led to more frequent diagnosis in term neonates, with RDS accounting for 6.8% of RD cases in term or near-term infants.[2]
Non-invasive assistance, such as nasal continuous positive airway pressure (NCPAP), has become a typical early intervention to lessen lung damage from mechanical ventilation. Despite its effectiveness, NCPAP has disadvantages such as low tolerance and nasal damage. The use of heated humidified high-flow nasal cannulas (HHHFNCs) in neonatal intensive care units (NICUs) has increased because they provide a positive pressure with greater comfort and fewer problems. However, evidence supporting HHHFNC as primary support remains limited. This study aims to compare outcomes of neonates started on HHHFNC or NCPAP.[3]
Cardiorespiratory transition in neonates
Transition from foetal to neonatal life involves replacement of alveolar fluid with air, initiation of breathing, and elevated pulmonary blood flow due to reduced pulmonary vascular resistance. These changes raise PaO2 from ~25 to 60–80 mmHg, promoting regular breathing. However, ~10% of neonates may have difficulty due to conditions such as fluid retention, congenital anomalies, or apnoea.
RD
A common reason for NICU admission, RD affects 15% of term and 29% of late preterm infants. It is identified by signs such as tachypnoea, nasal flaring, retractions, or grunting. Tachypnoea (respiratory rate [RR] >60/min) is a compensatory response to hypoxemia, hypercarbia, or acidosis. Poor lung compliance or increased airway resistance increases the work of breathing. Conditions such as RDS, transient tachypnoea of the newborn (TTN), pneumonia, or meconium aspiration syndrome (MAS) reduce compliance and tidal volume, necessitating higher RRs. If unmanaged, respiratory failure may occur.[4]
Pathogenesis
Causes of RD include developmental anomalies (e.g., tracheoesophageal fistula [TEF], pulmonary hypoplasia) or transitional disorders (e.g., TTN, RDS, MAS, persistent pulmonary hypertension [PPHN]). Lung development continues postnatally, and disorders such as bronchopulmonary dysplasia (BPD) may arise due to premature exposure to oxygen and ventilation, affecting up to 32% of preterm infants.
Grading severity
Silverman assesses severity–Anderson and Downes’ scores. Increasing FiO2 requirements to maintain saturation is also a sensitive indicator.[5]
Investigations
Essential investigations include chest X-ray, arterial blood gas (ABG), sepsis screen, blood glucose, calcium, haematocrit, and cultures. ABG score ≥3 or specific gas parameters indicate the need for continuous positive airway pressure (CPAP) or ventilation.
Management
Initial steps include airway clearance, oxygen support (head box or nasal cannula), thermal regulation, and pulse oximetry guided by the ‘30-60-90 rule’. Electrolyte, glucose, and calcium management are crucial. Maintain packed cell volume >40%. Start broad-spectrum antibiotics in all preterm and term neonates, based on clinical context.
Pathogenesis
Neonatal RD results from developmental, structural, or transitional disturbances in lung function. Lung maturation continues postnatally up to 2–5 years, making preterm infants vulnerable.[6] Disorders such as TTN, RDS, MAS, pneumonia, and PPHN stem from impaired perinatal transition, while anomalies such as TEF or pulmonary hypoplasia cause developmental distress. BPD represents chronic lung injury due to interrupted alveolarisation from oxygen toxicity and ventilation, affecting up to 50% of very low-birth-weight infants.[7]
Grading of distress severity
Severity is assessed using Silverman–Anderson and Downes’ scores. Regular scoring and FiO2 monitoring help track progression, with rising oxygen needs indicating worsening distress.[8]
Mechanical ventilation–associated morbidities
In neonates, particularly preterm, invasive mechanical ventilation (IMV) is linked with major morbidities, chiefly BPD and brain injury, owing to inflammatory and haemodynamic effects.
Non-invasive ventilation (NIV)
Since the 2000s, NIV has increasingly replaced IMV to prevent lung injury in RDS, especially in extremely preterm infants.[9]
NCPAP
Introduced by Gregory et al.[10] (1971), NCPAP enhances alveolar recruitment, improves compliance, and reduces apnoea. Meta-analyses show NCPAP lowers BPD, death, and surfactant use compared to IMV. Complications include air leaks, intraventricular haemorrhage (IVH), nasal trauma, and renal effects.
High-flow nasal cannula (HFNC)/HHHFNC
HFNC delivers warm, humidified gas (2–8 L/min), reducing airway resistance and nasal trauma. However, evidence is mixed. Some of the trials show higher failure rates with HFNC versus NCPAP, while meta-analyses indicate comparable efficacy with fewer complications.[11]
Randomised controlled trial (Yoder et al.;[12] Lavizzari et al.;[11] Hegde et al.;[13] Shin et al.[14]) consistently found HHHFNC non-inferior to NCPAP for mild–moderate RDS ≥28 weeks GA, with similar intubation rates and significantly less nasal trauma.
Overall, while NIV, especially NCPAP and HHHFNC, has reduced IMV-related complications, optimal mode selection depends on gestational age, disease severity, and local expertise.
Aim
To evaluate the outcomes of newborns with RD managed primarily with HHHFNC or NCPAP.
Objectives
To compare morbidities such as FiO2 requirement, requirement of mechanical ventilation, and duration of respiratory support between the two groups.
To compare baseline clinical characteristics such as time to reach full feeds, gestational age, birth weight, duration of hospital stays, and feeding intolerance amongst newborns managed with HHHFNC or NCPAP.
To assess and compare the side effects associated with both modes of therapy.
MATERIAL AND METHODS
Study area
Department of paediatrics, medical college, and general hospital.
Study population
Newborn with gestational age <42 weeks admitted with RD within the first 12 h of birth.
Study design
This was a hospital-based prospective comparative interventional study.
Sample size
n = (DEFF ×Np [1−p])/([d2/Z21-α/2 × [N−1] + p × [1−p])
| Population size (for finite population correction factor or fpc) (N) | 1000000 |
| Hypothesised % frequency of outcome factor in the population (P) | 7%±5 |
| Confidence limits as % of 100 (Absolute ± %) (d) | 5% |
| Design effect (for cluster surveys-DEFF) | 1 |
| n – 101 newborns |
Study duration
The study duration was from November 2022 to April 2023.
Inclusion criteria
Newborns with gestational age <42 weeks admitted with RD within the first 12 h of birth.
Exclusion criteria
Neonates with an Apgar score <5 at admission.
Neonates with nasopharyngeal pathologies (choanal atresia, cleft lip/palate), the most important congenital malformations, congenital heart disease, or surgical conditions causing RD (e.g., pneumothorax, congenital diaphragmatic hernia).
Neonates whose parents or guardians declined consent.
Methodology
In the Special Newborn Care Unit, Department of Paediatrics, Medical College, a prospective comparative interventional study was carried out.
The Central Research Committee and the Institutional Ethics Committee (IEC) provided their ethical approval.
In front of a witness, parents provided written informed consent.
Included were 101 infants (gestational age <42 weeks) who were taken in with RD during the first 12 h of life.
Four HHHFNC and four bubble NCPAP devices were installed in the unit, and eligible neonates were randomised using the chit method to either the HHHFNC or NCPAP groups.
Definition of mild-to-moderate RD
Preterm infants: Arterial pH >7.2, PaCO2 <60 mmHg, FiO2 ≤60% to maintain SpO2 88–93% and Silverman– Anderson Score (SAS) 3–6.
Term infants: Arterial pH >7.2, PaCO2 <60 mmHg, FiO2 ≤60% to maintain SpO2 88–93% and Downes’ Score 3–6.
Criteria for failure of HHHFNC or NCPAP
Failure was defined as the presence of one or more of the following:
SpO2 ≤60% despite FiO2 >60%, flow >6 L/min (HHHFNC) or positive end-expiratory pressure (PEEP) >7 cm H2O (NCPAP).
SAS score >6 irrespective of maximal settings.
Recurrent apnoea (>3 episodes/24 h) or any episode that needs bag-mask ventilation.
pH <7.2 or PaCO2 >60 mmHg.
Need for inotropic support.
Infants meeting failure criteria were intubated and mechanically ventilated.
Surfactant administration
Exogenous surfactant (100 mg/kg) was administered using the Intubate–Surfactant–Extubate technique if FiO2 ≥40% in 2 h of initiating HHHFNC/NCPAP.
HHHFNC group
The MR850 humidifier (Fisher and Paykel Healthcare) and RT329 Infant Oxygen Therapy Circuit were used together with short nasal prongs (≤50% of nare diameter).
FiO2 was titrated (maximum 60%) to maintain SpO2 between 88 and 93% after starting at 3 L/min.
If the discomfort continued, the flow was raised by 1 L/min increments up to 6 L/min.
Weaning: Before stopping, gradually reduce FiO2 to 21% and flow to 1 L/min.
NCPAP group
Provided using a Bubble CPAP machine (BC 151, Fisher and Paykel Healthcare) equipped with Hudson short binasal prongs and an MR850 humidifier
Started at 5 cm H2O pressure, flowed 6 L/min, and regulated FiO2 (maximum 60%) to keep SpO2 between 88% and 93%
To guarantee sufficient bubbling, pressure was raised to 7 cm H2O, and flow was increased to 8 L/min
Weaning criteria: [15] PEEP <5 cm H2O, SpO2 >90% on FiO2 <30%, RR 40–60/min, and minimal distress (SAS 0–1)
FiO2 was lowered by 5% increments to 21% during the weaning process, and CPAP was lowered to 4 cm H2O before removal.
Data collection
Maternal data: Antenatal complications, mode of delivery, steroid use
Neonatal data: Birth weight, gestational age (based on last menstrual period/ultrasound/New Ballard score), intrauterine growth restriction status, need for resuscitation, chest X-ray findings, ABG results, FiO2 requirement, and SAS at 30 min post-initiation.
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Definitions:
BPD: As per the NIH consensus definition
IVH: As per Papile classification
Necrotising enterocolitis (NEC): Bell’s modified classification (Stage ≥II)
Retinopathy of prematurity: International classification of retinopathy of prematurity
Full feeds: 150 mL/kg/day.
Statistical analysis
A pre-made study pro forma was used to record all of the data. The Chi-square test was used to examine correlations between the qualitative variables, which were expressed as frequency and percentage. Mean ± standard deviation was used to display quantitative data. The Mann–Whitney U test for non-normal data and the unpaired t-test for normally distributed data were used for between-group comparisons. Statistical significance was defined as a p < 0.05. Statistical Package for the Social Sciences Version 26.0 was used for the analyses, and Microsoft Excel 2021 was used to create the graphs.
Ethical issues
Ethical approval for the study was obtained from the IEC. All collected information was kept confidential and used solely for research purposes. Following an explanation of the study’s objectives and methods, parents or guardians provided written informed consent. The annexure contains the Participant Information Sheet and Consent Form.
RESULTS
The study included 101 newborns who were admitted with RD. They were divided into two groups of management, i.e., one group which was initiated on HFNC (n-51 cases) and another group initiated on NCPAP (n-50) as a primary mode of respiratory support. Amongst the 101 newborns, 48 (47.5%) were female, and 53 (52.5%) were male. In the NCPAP group, there were 24 females (48%) and 26 males (52%), while in the HHHFNC group, there were 24 females (47.1%) and 27 males (52.9%). The distribution of gender between the two groups was similar (ρ = 1.0).
While the SAS score is frequently utilised for preterm neonates, the Downes scoring system is employed for term neonates. A score of zero indicates no RD, one to four indicates mild RD, five to seven indicates moderate RD, and more than seven indicates serious distress or imminent respiratory failure. In the present study, all the neonates were of mild RD. Comparison of both groups as per severity scoring is shown in Table 1.
| SAS/Downe score | Group | Total | |
|---|---|---|---|
| NCPAP | HFNC | ||
| 2 | 4 | 7 | 11 |
| 8.0% | 13.7% | 10.9% | |
| 3 | 23 | 22 | 45 |
| 46.0% | 43.1% | 44.6% | |
| 4 | 23 | 22 | 45 |
| 46.0% | 43.1% | 44.6% | |
| Total | 50 | 51 | 101 |
| 100.0% | 100.0% | 100.0% | |
p=0.65, HFNC: High-flow nasal cannula, NCPAP: Nasal continuous positive airway pressure, SAS: Silverman–Anderson score
Overall complication rate was comparable between study groups (ρ > 0.05). Incidence of sepsis was 36% and 31.4% in the NCPAP and HFNC group (ρ = 0.67). Other complications were (IVH – 8% vs. 5.9%), NEC (12% vs. 4%), and BPD (2% each). The incidence of nasal trauma was significantly higher in cases of NCPAP as compared to HFNC (8% vs. 0%; ρ = 0.04), as shown in Table 2.
| Complications | Group | Total | p-value | |
|---|---|---|---|---|
| NCPAP | HFNC | |||
| Sepsis | 18 | 16 | 34 | 0.67 |
| 36.0% | 31.4% | 33.7% | ||
| IVH | 4 | 3 | 7 | 1.00 |
| 8.0% | 5.9% | 6.9% | ||
| NEC | 6 | 4 | 10 | 0.48 |
| 12.0% | 7.8% | 9.9% | ||
| ROP | 0 | 0 | 0 | NA |
| 0.0% | 0.0% | 0.0% | ||
| BPD | 1 | 1 | 2 | 1.00 |
| 2.0% | 2.0% | 2.0% | ||
| Nasal trauma | 4 | 0 | 4 | 0.04 |
| 8.0% | 0.0% | 4.0% | ||
BPD: Bronchopulmonary dysplasia, HFNC: High-flow nasal cannula, NCPAP: Nasal continuous positive airway pressure, IVH: Intraventricular haemorrhage, NEC: Necrotising enterocolitis, ROP: Retinopathy of prematurity; NA: Not available; p<0.05 was considered statistically significant
Out of 101 newborns, 31 (30.7%) received surfactant while 70 (69.3%) did not. In the NCPAP group, 15 (30%) received surfactant, and 35 (70%) did not, whereas in the HHHFNC group, 16 (31.4%) received surfactant and 35 (68.6%) did not. There was no statistically significant difference between the groups (ρ= 1.0).
Surfactants were required in 30% and 31.4% cases of NCPAP and HFNC, respectively (ρ = 1.0), as depicted in Figure 1.
Both the groups were comparable with regards to mean duration of respiratory support and duration of hospital stay for term as well as pre-term babies (ρ > 0.05), as shown in Table 3. The mean time required to return to full feeds was significantly faster in pre-term cases initiated on HFNC (3.87 vs. 4.88; p = 0.02). However, no difference was seen in term babies (ρ = 0.81).
| Duration | Group | n | Mean | Standard deviation | p-value |
|---|---|---|---|---|---|
| Pre-term | |||||
| Respiratory support (days) | NCPAP | 41 | 1.22 | 1.31 | 0.18 |
| HFNC | 46 | 1.71 | 1.91 | ||
| Time to full feeds (days) | NCPAP | 41 | 4.88 | 2.20 | 0.02 |
| HFNC | 46 | 3.87 | 1.86 | ||
| Hospitalisation (days) | NCPAP | 41 | 10.54 | 8.81 | 0.33 |
| HFNC | 46 | 12.43 | 9.10 | ||
| Term | |||||
| Respiratory support (days) | NCPAP | 9 | 1.28 | 1.00 | 0.34 |
| HFNC | 5 | 1.95 | 1.52 | ||
| Time to full feeds (days) | NCPAP | 9 | 4.50 | 1.56 | 0.81 |
| HFNC | 5 | 4.25 | 2.17 | ||
| Hospitalisation (days) | NCPAP | 9 | 12.89 | 8.07 | 0.12 |
| HFNC | 5 | 6.40 | 3.78 |
HFNC: High-flow nasal cannula, NCPAP: Nasal continuous positive airway pressure; p<0.05 was considered statistically significant
On overall comparison, both the groups were comparable with regard to mean duration of respiratory support and duration of hospital stay (p > 0.05) [Table 4]. Mean time required to return to full feeds was significantly faster in cases initiated on HFNC (3.98 vs. 4.82; p = 0.04).
| Duration | Group | n | Mean | Standard deviation | p-value |
|---|---|---|---|---|---|
| Respiratory support (days) | NCPAP | 50 | 1.23 | 1.25 | 0.12 |
| HFNC | 51 | 1.73 | 1.87 | ||
| Time to full feeds (days) | NCPAP | 50 | 4.82 | 2.18 | 0.04 |
| HFNC | 51 | 3.98 | 1.82 | ||
| Hospitalisation (days) | NCPAP | 50 | 10.96 | 8.65 | 0.61 |
| HFNC | 51 | 11.84 | 8.89 |
HFNC: High-flow nasal cannula, NCPAP: Nasal continuous positive airway pressure; p<0.05 was considered statistically significant
Out of 101 newborns, 33 (32.7%) required ventilatory support while 68 (67.3%) did not. In the NCPAP group, 20 (40%) required ventilatory support and 30 (60%) did not, whereas in the HHHFNC group, 13 (25.5%) required ventilatory support and 38 (74.5%) did not. The difference between the groups was not statistically significant (ρ = 0.149). Ventilator support was required in 40% cases initiated in NCPAP as compared to 25.5% cases initiated in HFNC, respectively (ρ = 0.149).
Amongst 87 pre-term infants, 60 (69.0%) did not require ventilatory support, and 27 (31.0%) did. In the NCPAP group, 26 (63.4%) did not require support, and 15 (36.6%) did, while in the HHHFNC group, 34 (73.9%) did not require support and 12 (26.1%) did, as shown in Figure 2. This difference was not statistically significant (ρ = 0.49). Amongst 14 term infants, 8 (57.1%) did not require ventilatory support, and 6 (42.9%) did. In the NCPAP group, 4 (44.4%) did not require support, and 5 (55.6%) did, while in the HHHFNC group, 4 (80.0%) did not require support, and 1 (20.0%) did. This difference was statistically significant (ρ = 0.03). Amongst pre-term babies, 36.6% required ventilator support after they were put on NCPAP, as compared to 27.9% babies who were put on HFNC. The difference was statistically non-significant (ρ = 0.49) [Figure 2]. However, amongst term babies, a significantly lower number of babies required a ventilator when put on HFNC (20%) as compared to NCPAP (55.6%) (ρ = 0.03).
Out of 101 infants, 93 (92.1%) were discharged, and 8 (7.9%) died. In the NCPAP group, 46 (92.0%) were discharged, and 4 (8.0%) died, while in the HHHFNC group, 47 (92.2%) were discharged and 4 (7.8%) died. There was no statistically significant difference between the groups (ρ = 1.0).
Overall mortality rate was comparable amongst babies put on either NCPAP or HFNC (8% vs. 7.8%; p = 1.0).
DISCUSSION
One of the main causes of newborn death is RDS. While heated HHHFNC offer comparable support with fewer restrictions, non-invasive respiratory support in particular, NCPAP is frequently utilised to lessen lung harm.[16-19] In this study of 101 newborns with RD (51 HHHFNC, 50 NCPAP), baseline characteristics including gestational age, birth weight, and severity of distress were comparable.
HHHFNC and NCPAP groups showed similar outcomes regarding surfactant use, duration of respiratory support, hospital stay, sepsis, and mortality. Time to full feeds was significantly shorter in HHHFNC overall (3.98 vs. 4.82 days; ρ = 0.04), especially in preterm infants. Nasal trauma was significantly lower with HHHFNC (0% vs. 8%; ρ = 0.04).[20] Ventilator requirement was lower in HHHFNC (25.5% vs. 40%), consistent with previous studies: Yoder et al.[12] (44% vs. 46%), Hegde et al.[13] (19.5% vs. 26.2%), Shin et al.[14] (38% vs. 20.9%). Amongst term infants, this difference was significant (20% vs. 55.6%; ρ = 0.03).
CONCLUSION
HHHFNC is as effective as NCPAP for primary respiratory support in infants with mild RD. Both modalities showed comparable duration of oxygen therapy and ventilator requirement. HFNC was associated with significantly lower nasal trauma and faster resumption of enteral feeding. It is easy to use and well-tolerated. Further large-scale, multicentric studies are needed to confirm these findings.
Ethical approval:
The research/study was approved by the Institutional Review Board at GMERS Medical College, Gandhinagar, number 2406, dated 20 March 2023.
Declaration of patient consent:
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given consent for clinical information to be reported in the journal. The patient understands that the patient’s names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Conflicts of interest:
There are no conflicts of interest.
Use of artificial intelligence (AI)-assisted technology for manuscript preparation:
The authors confirm that there was no use of artificial intelligence (AI)-assisted technology for assisting in the writing or editing of the manuscript, and no images were manipulated using AI.
Financial support and sponsorship: Nil.
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