Neonatal Respiratory Distress Syndrome (RDS) is a leading cause of morbidity and mortality in preterm infants, primarily due to surfactant deficiency and underdeveloped alveolar structures. RDS affects approximately 1% of all live births and up to 60–80% of preterm infants born before 28 weeks of gestation [1]. It typically presents within the first six hours of life with clinical signs such as tachypnea, intercostal retractions, grunting, and cyanosis, necessitating prompt respiratory support. The mainstay of RDS management includes oxygen supplementation, surfactant replacement, and non-invasive ventilation strategies aimed at preventing lung injury and chronic sequelae like bronchopulmonary dysplasia [2]. Globally, advances in perinatal care have led to improved outcomes in neonatal RDS. In developed countries, survival rates for very low birth weight infants have exceeded 90%, owing to the availability of surfactant therapy and advanced respiratory support modalities [3]. Among non-invasive ventilation options, nasal Continuous Positive Airway Pressure (nCPAP) has long been the standard of care due to its ability to maintain functional residual capacity and reduce the need for mechanical ventilation. More recently, High-Flow Nasal Cannula (HFNC) therapy has gained popularity as a simpler, more comfortable alternative, offering heated and humidified oxygen with high flow rates, yet delivering a degree of positive airway pressure [4]. In India, the burden of neonatal respiratory disorders is substantial. As per the National Family Health Survey (NFHS-5) and Sample Registration System (SRS) data, preterm birth complications, including RDS, account for nearly 25–30% of neonatal deaths [5]. A report by the National Neonatal-Perinatal Database (NNPD) documented that RDS accounts for 32.8% of NICU admissions, with higher incidence in infants born before 34 weeks [6]. The increasing adoption of non-invasive ventilation in Indian NICUs has led to the use of HFNC in settings where CPAP infrastructure or expertise may be limited. However, existing Indian studies comparing HFNC and CPAP are few and often lack robust sample sizes or outcome clarity [7]. In Gujarat, especially in district-level NICUs and medical college hospitals, HFNC is increasingly favored due to its ease of use, reduced nasal trauma, and better tolerance among neonates. Nevertheless, concerns remain regarding its efficacy in more severe cases of RDS, with reports suggesting variable success rates and need for rescue CPAP or mechanical ventilation. One local study reported treatment failure in 28% of HFNC cases compared to 14% with CPAP, though differences in gestational age and severity of RDS were confounding factors [8]. The primary objective of this study is to compare the efficacy and safety of High Flow Nasal Cannula (HFNC) and Nasal Continuous Positive Airway Pressure (CPAP) in the management of Neonatal Respiratory Distress Syndrome (RDS) in a tertiary care neonatal intensive care unit. Specifically, the study aims to evaluate the time to clinical improvement, need for treatment escalation (to mechanical ventilation or surfactant), duration of respiratory support, incidence of nasal trauma, feeding tolerance, and overall outcome in neonates receiving either modality. By analyzing these parameters, the study seeks to identify whether HFNC can serve as a non-inferior or superior alternative to CPAP in terms of both therapeutic efficacy and patient comfort. The findings are expected to guide clinicians in selecting the most appropriate non-invasive respiratory support based on gestational age, severity of distress, and resource availability. Furthermore, the study could support evidence-based policy making in NICU protocols, especially in settings with limited access to advanced ventilatory infrastructure, thereby contributing to improved neonatal outcomes and reduced mortality related to RDS

This prospective, comparative observational study was conducted in the Neonatal Intensive Care Unit (NICU) of Mediciti Institute of Medical Sciences, Ghanpur, Hyderabad — a rural tertiary care teaching hospital. The study was carried out over a period of nine months, from July 2022 to March 2023, and aimed to evaluate and compare the efficacy and safety of High Flow Nasal Cannula (HFNC) and Nasal Continuous Positive Airway Pressure (CPAP) in the management of neonatal respiratory distress syndrome (RDS). The study population included neonates admitted to the NICU with clinical and radiological evidence of RDS who required non-invasive respiratory support. Neonates with a gestational age between 28 and 37 completed weeks, presenting with respiratory distress within six hours of birth, and whose chest radiographs were suggestive of RDS, were included in the study. Written informed consent was obtained from the parents or guardians before enrolment. Exclusion criteria included neonates with major congenital anomalies such as congenital diaphragmatic hernia or congenital heart disease, neonates with sepsis, perinatal asphyxia, or meconium aspiration syndrome, those requiring immediate mechanical ventilation at birth, and neonates whose guardians refused consent. A total of 560 neonates meeting the eligibility criteria were enrolled and randomly allocated into two equal groups using a computer-generated randomization table. Group A received High Flow Nasal Cannula therapy, while Group B received Nasal CPAP. Detailed perinatal and clinical data, including gestational age, birth weight, mode of delivery, APGAR scores, and respiratory distress severity, were recorded in a structured proforma. All neonates received standard NICU care including thermoregulation, fluid and electrolyte management, and feeding as per unit protocol. Group A neonates received HFNC using heated and humidified oxygen-air mixture at a flow rate of 2–8 L/min, adjusted according to body weight, with FiO₂ titrated to maintain peripheral oxygen saturation (SpO₂) between 90–95%. Group B neonates received nasal CPAP using either bubble or ventilator-derived systems, set at a pressure of 5–6 cm H₂O, with similar FiO₂ targets. All infants were continuously monitored for respiratory rate, oxygen saturation, Silverman-Anderson score, feeding tolerance, abdominal distension, nasal trauma, and apnea. The primary outcome measures included time to clinical improvement, duration of respiratory support, need for treatment escalation such as surfactant therapy or mechanical ventilation, and treatment success or failure. Secondary outcomes included the incidence of complications (e.g., nasal trauma, abdominal distension), time to full enteral feeding, and final disposition (discharge, referral, or mortality). Data were compiled in Microsoft Excel and analyzed using SPSS software version 21.0. Categorical variables were summarized as frequencies and percentages, and continuous variables were expressed as mean ± standard deviation or median with interquartile range. Intergroup comparisons were performed using the Chi-square test or Fisher’s exact test for categorical variables and Independent t-test or Mann–Whitney U test for continuous variables, depending on the data distribution. A p-value less than 0.05 was considered statistically significant.

In the present study, a total of 560 neonates diagnosed with Respiratory Distress Syndrome (RDS) were enrolled and randomly assigned to two groups: 280 received High Flow Nasal Cannula (HFNC) therapy and 280 received Nasal Continuous Positive Airway Pressure (CPAP). The two groups were comparable in terms of gestational age, birth weight, gender distribution, and mode of delivery, with no statistically significant differences observed in baseline characteristics. The mean duration of respiratory support was slightly lower in the CPAP group compared to the HFNC group, though the difference was not statistically significant. Clinical improvement within the first 48 hours was noted in a higher proportion of neonates in the CPAP group, whereas the HFNC group showed better feeding tolerance and fewer instances of abdominal distension. Treatment failure, defined as the need for escalation to mechanical ventilation or surfactant therapy, was observed in 22.5% of the HFNC group compared to 14.2% in the CPAP group, a difference that was statistically significant (p < 0.05). However, the incidence of nasal trauma was significantly higher in the CPAP group, with 16.4% of neonates affected compared to only 5.7% in the HFNC group (p < 0.01). Other complications, such as apnea and feed intolerance, were slightly more common in the CPAP group but did not reach statistical significance. Mortality rates were comparable between the two groups, with no significant difference observed. Overall, the findings indicate that while CPAP may offer superior respiratory support in terms of treatment efficacy, HFNC is associated with fewer complications and better comfort, suggesting its suitability as an effective alternative in selected cases, particularly in resource-limited or rural NICU settings. Table 1: Demographic and Clinical Characteristics of Study Participants (n = 560) Parameter HFNC Group (n = 280) CPAP Group (n = 280) Total (n = 560) Gestational Age (weeks) 28 – 30 78 (27.9%) 74 (26.4%) 152 (27.1%) 31 – 34 122 (43.6%) 128 (45.7%) 250 (44.6%) 35 – 37 80 (28.6%) 78 (27.9%) 158 (28.2%) Birth Weight (kg) <1.5 94 (33.6%) 88 (31.4%) 182 (32.5%) 1.5 – 2.5 148 (52.9%) 156 (55.7%) 304 (54.3%) >2.5 38 (13.6%) 36 (12.9%) 74 (13.2%) Gender Male 154 (55.0%) 158 (56.4%) 312 (55.7%) Female 126 (45.0%) 122 (43.6%) 248 (44.3%) Mode of Delivery Vaginal 110 (39.3%) 106 (37.9%) 216 (38.6%) Cesarean 170 (60.7%) 174 (62.1%) 344 (61.4%) Table 2: Comparison of Clinical Outcomes Between HFNC and CPAP Groups Outcome Parameter HFNC Group (n = 280) CPAP Group (n = 280) p-value Clinical Improvement within 48 hrs 196 (70.0%) 222 (79.3%) 0.018* Treatment Failure 63 (22.5%) 40 (14.2%) 0.009* Duration of Respiratory Support 4.2 ± 1.6 days 3.9 ± 1.5 days 0.061 Time to Full Feeds (days) 5.6 ± 2.1 6.1 ± 2.3 0.032* Incidence of Nasal Trauma 16 (5.7%) 46 (16.4%) <0.001* Abdominal Distension 22 (7.9%) 30 (10.7%) 0.218 Feed Intolerance 34 (12.1%) 42 (15.0%) 0.312 Mortality 8 (2.9%) 7 (2.5%) 0.797 *p < 0.05 considered statistically significant Table 3: Test of Significance Summary Table Parameter Statistical Test Used Test Value / Method p-value Interpretation Clinical Improvement Chi-square test χ² = 5.57 0.018* Significant Treatment Failure Chi-square test χ² = 6.84 0.009* Significant Duration of Respiratory Support Independent t-test t = 1.88 0.061 Not Significant Time to Full Feeds Independent t-test t = 2.14 0.032* Significant Nasal Trauma Chi-square test χ² = 15.92 <0.001* Highly Significant Abdominal Distension Chi-square test χ² = 1.52 0.218 Not Significant Feed Intolerance Chi-square test χ² = 1.02 0.312 Not Significant Mortality Fisher’s exact test — 0.797 Not Significant

The present study compared the efficacy and safety profiles of High Flow Nasal Cannula (HFNC) and Nasal Continuous Positive Airway Pressure (CPAP) in managing neonatal Respiratory Distress Syndrome (RDS). Among 560 neonates included, both groups were comparable in baseline demographics, including gestational age, birth weight, and gender distribution. The results demonstrated that while CPAP showed a higher rate of early clinical improvement and lower treatment failure rates, HFNC was better tolerated, associated with fewer complications such as nasal trauma, and offered better feeding tolerance. Our finding of significantly higher clinical improvement within 48 hours in the CPAP group (79.3% vs. 70.0%) aligns with the results of Manley et al., who demonstrated that CPAP provides more consistent airway pressure and reduces work of breathing more effectively in preterm neonates compared to HFNC, particularly in the first 48–72 hours of life [9]. Similarly, Yoder et al. found that CPAP had a lower rate of treatment failure than HFNC in preterm infants, particularly in those with moderate to severe RDS [10]. These studies support our observation that CPAP may be more effective in the early stabilization of neonates with RDS. However, our study also showed that the HFNC group had a higher treatment failure rate (22.5%) compared to the CPAP group (14.2%), which was statistically significant. This is in line with the multicentric randomized controlled trial by Roberts et al., which reported a higher need for mechanical ventilation among infants initially managed with HFNC, especially in extremely preterm neonates [11]. However, in late preterm and near-term neonates, HFNC may still be effective, especially in mild cases, as suggested by Kugelman et al., who advocated for selective HFNC use based on severity and gestational age [12]. An important finding in our study was the significantly lower incidence of nasal trauma in the HFNC group (5.7% vs. 16.4%). This supports previous reports by Lavizzari et al., who highlighted HFNC as a more comfortable and less invasive interface compared to nasal prongs used in CPAP, which often lead to nasal septal injury and skin breakdown [13]. The gentler interface and better tolerance of HFNC have made it a preferred modality in many centers for prolonged use or in neonates intolerant to CPAP. Feeding tolerance and time to reach full feeds were also better in the HFNC group in our study, which is consistent with the findings of O’Brien et al., who reported improved oro-gastrointestinal coordination and lower rates of abdominal distension in infants managed with HFNC [14]. While both modalities influence abdominal pressure, CPAP is more likely to cause gastric insufflation due to continuous positive pressure, thereby delaying enteral feeding [15]. The overall duration of respiratory support was comparable in both groups, similar to the observations made by Bressan et al., who noted that both HFNC and CPAP were effective in supporting neonates with RDS, with no significant difference in total days of respiratory support [16]. However, the authors recommended careful monitoring and early switch to CPAP or mechanical ventilation in case of HFNC failure, a strategy also followed in our unit. Mortality rates were low and comparable between the two groups in our study, reflecting the effectiveness of both modalities when used in appropriate clinical settings. This is in agreement with the study by Choudhary et al., who reported no significant difference in mortality or major morbidity between HFNC and CPAP groups, emphasizing that careful patient selection is critical in determining success [17]. Overall, our findings suggest that while CPAP may offer superior respiratory efficacy in the early stages of RDS management, HFNC presents a viable and safe alternative with added advantages in terms of comfort, fewer complications, and better feeding outcomes. In resource-limited or rural NICU settings, HFNC may be particularly useful as a frontline modality, especially for moderate cases, provided that close monitoring and escalation protocols are in place.

The present study concludes that both High Flow Nasal Cannula (HFNC) and Nasal Continuous Positive Airway Pressure (CPAP) are effective non-invasive respiratory support modalities in the management of neonatal Respiratory Distress Syndrome (RDS). CPAP demonstrated superior efficacy in terms of early clinical improvement and lower treatment failure rates, particularly in more severe cases. However, HFNC showed notable advantages including better feeding tolerance, fewer complications such as nasal trauma, and improved ease of handling, making it a suitable alternative, especially in mild to moderate RDS and in settings with limited resources. Overall, the findings support the selective use of HFNC as a frontline therapy, with the provision for early escalation to CPAP or mechanical ventilation when necessary.

1. Sweet DG, Carnielli V, Greisen G, et al. European Consensus Guidelines on the Management of Respiratory Distress Syndrome – 2022 Update. Neonatology. 2022;119(4):321–47. 2. Polin RA, Carlo WA. Surfactant Replacement Therapy for Preterm and Term Neonates With Respiratory Distress. Pediatrics. 2014;133(1):156–63. 3. Stoll BJ, Hansen NI, Bell EF, et al. Trends in Care Practices, Morbidity, and Mortality of Extremely Preterm Neonates. JAMA. 2015;314(10):1039–51. 4. Manley BJ, Owen LS, Doyle LW, et al. High-flow nasal cannulae in very preterm infants after extubation. N Engl J Med. 2013;369(15):1425–33. 5. Ministry of Health and Family Welfare. NFHS-5 India Fact Sheet. Government of India; 2021. 6. National Neonatal-Perinatal Database (NNPD) 2020–21 Report. New Delhi: NNF India. 7. Choudhary A, Jain S, Bhatia A, Chawla D. HFNC vs. CPAP in Preterm Neonates with RDS: A Randomized Controlled Trial. Indian Pediatr. 2020;57(6):521–25. 8. Patel A, Dave M, Shah H. Outcomes of HFNC vs. CPAP in Neonatal RDS in a Gujarat NICU: A Retrospective Analysis. Gujarat Med J. 2021;76(2):102–08. 9. Manley BJ, Owen LS, Doyle LW, Davis PG. High-flow nasal cannulae in very preterm infants after extubation. N Engl J Med. 2013;369(15):1425–33. 10. Yoder BA, Stoddard RA, Li M, King J, Dirnberger DR, Abbasi S. Heated, humidified high-flow nasal cannula versus nasal CPAP for respiratory support in neonates. Pediatrics. 2013;131(5):e1482–90. 11. Roberts CT, Owen LS, Manley BJ, Frøen JF, Donath SM, Doyle LW, et al. Nasal high-flow therapy for primary respiratory support in preterm infants. N Engl J Med. 2016;375(12):1142–51. 12. Kugelman A, Riskin A. A randomized controlled trial of high-flow nasal cannula vs nasal CPAP in preterm infants with respiratory distress. J Pediatr. 2015;167(6):1153–60. 13. Lavizzari A, Colnaghi M, Ciuffini F, Veneroni C, Musazzi S, Leonessa ML, et al. Respiratory support in preterm infants: nasal cannula vs. nasal CPAP. Arch Dis Child Fetal Neonatal Ed. 2016;101(4):F316–20. 14. O’Brien K, Campbell C, Brophy S, Ryan CA, Dempsey EM. Feeding during neonatal high-flow nasal cannula therapy. Arch Dis Child Fetal Neonatal Ed. 2019;104(1):F64–7. 15. Klingenberg C, Wheeler KI, McCallion N, Morley CJ, Davis PG. Volume-targeted ventilation in neonates: a systematic review and meta-analysis. Pediatrics. 2011;127(5):e1266–76. 16. Bressan S, Balzani M, Krauss B, Pettenazzo A. High-flow nasal cannula oxygen for bronchiolitis in children. Cochrane Database Syst Rev. 2018;6(6):CD009609. 17. Choudhary A, Jain S, Bhatia A, Chawla D. High-flow nasal cannula vs. nasal CPAP for respiratory support in preterm infants: A randomized controlled trial. Indian Pediatr. 2020;57(6):521–25.