Nasal high-frequency oscillatory ventilation versus nasal continuous positive airway pressure as primary respiratory support strategies for respiratory distress syndrome in preterm infants: a systematic review and meta-analysis

Abstract

Nasal high-frequency oscillatory ventilation (NHFOV) has been described to be an advanced version of nasal continuous positive airway pressure (NCPAP). However, its beneficial effects among different studies were inconsistent. The aim of the present study was to assess the effects between NHFOV and NCPAP as the primary respiratory supporting strategies on the intubation rate in preterm infants with respiratory distress syndrome(RDS). Medline, the Cochrane library, the Cochrane Controlled Trials Register, EMBASE, Chinese National Knowledge Infrastructure (CNKI), and Wanfang data Information Site were searched from inception to Jan 1, 2021(Prospero2019 CRD42019129316, date of registration:Apr-23,2019). Pooled data from clinically randomized controlled trials(RCTs) comparing NHFOV with NCPAP as the primary respiratory supporting strategies in preterm infants with RDS were performed using the fixed-effects models whenever no heterogeneity was shown. The primary outcome was intubation rate. Four randomized controlled trials involving 570 participants were included. Comparing with NCPAP, NHFOV resulted in less intubation rate(relative risk(RR):0.47; 95% confidence interval(CI):0.31–0.70, P = 0.0002), and heterogeneity was not found among the trials in the fixed effects model (P = 0.69, I² = 0%). Similar result also appeared in sensitivity analysis after excluding one study with significant difference(RR:0.49; 95% CI:0.29–0.81, P = 0.006) (P = 0.52, I² = 0%).

Conclusion NHFOV is superior to NCPAP in decreasing the risk of intubation as a primary respiratory supporting strategies in preterm infants suffering from RDS.

Introduction

Invasive ventilation(IV) is a key procedure to reduce respiratory mortality and morbidity in preterm infants with respiratory distress syndrome(RDS). However, it inhibits normal respiratory physiological process and is associated with the increased risks of bronchopulmonary dysplasia (BPD),[1] re-hospitalization and brain injury among the survivors.[2–4] How to avoid IV in early life is therefore a critical procedure to reduce respiratory mortality and morbidity.

To date, nasal continuous positive airway pressure(NCPAP) remains one widely used way of the noninvasive ventilation modes to avoid intubation in preterm infants. However, the failure rate is high and ranges from about 20–60%.[5–8] Nasal intermittent positive pressure ventilation (NIPPV) is another respiratory supporting strategy. Systematic review has proven that NIPPV is superior to NCPAP to avoid re-intubation in preterm infants after extubation.[7] However, early use of NIPPV was not shown beneficial effects for decreasing the need for intubation as compared with NCPAP alone in preterm infants with RDS. [5, 6]

Supplying with the combined advantages of NCPAP with higher mean airway pressure and NIPPV without need for synchronization, nasal high-frequency oscillatory ventilation (NHFOV) should be beneficial to reduce the incidences of re-intubation and complications in preterm infants.[9–11] A multicenter study has indicated that NHFOV was related to the reduced numbers of apnea, bradycardia and oxygen desaturation as a remedial measure after failing to other noninvasive modes in preterm infants.[12] And it was consistent with the previous small sample and non-randomized controlled studies.[13–15] Despite no compelling evidences about the safety and efficacy of NHFOV from multicenter randomized controlled trials, NHFOV was widely used and no obvious side effects were observed.[16] In 2017, we reported a small randomized controlled study, and the result showed that, comparing

with NCPAP, NHFOV was associated with lower rate of intubation as primary respiratory support strategy. [17] And it was consistent with the subgroup analysis of Shi et al., [18] of which NHFOV showed a lower rate of treatment failure than NCPAP in the strata of 26^+ 0 to 29^+ 6 weeks’ gestational age (11.9% vs 32.4%, 95%CI, 0.088 to 0.898, P = 0.032) and BW < 1500g (10.4% vs 29.6%, 95%CI, 0.104 to 0.736, P = 0.010). However, as far as the primary outcome was concerned, NHFOV was not shown to superior to NCPAP(9.9% vs 17.3%, 95%CI, 0.264 to 1.031, P = 0.066). And it was consistent with the report of Malakian et al., [19] in which NHFOV did not reduce the need for IV during the first 72 hours after birth as compared with NCPAP. Therefore, there was an urgent need to assess the beneficial effects between NHFOV and NCPAP on intubation rate and the other complications.

The purpose of the systematic review and meta-analysis was to evaluate whether NHFOV would reduce the need for intubation as compared with NCPAP in the treatment of preterm infants with RDS as the primary respiratory supporting mode.

Methods

The protocol of this systematic review and meta-analysis was registered before the studies search in PROSPERO (Prospero2019 CRD42019129316). And it was performed conforming to the Methodological Expectations of Cochrane Intervention Reviews and was shown in accordance with the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. [20]

Types of studies, eligibility criteria and interventions

The criteria for a trial to be included in the meta-analysis were as follows: (1) trial involving human newborn infants in the early stage of RDS, (2) trial comparing NHFOV with NCPAP as the primary respiratory support strategies, (3) it was a clinically randomized controlled trial. Only RCTs were included because they are the best design to obtain unbiased assessment of beneficial effects through restricting the known and underlying confounders affecting the primary and secondary outcomes.

The excluded criteria were: (1) trials involving animal or pre-clinical studies, (2) duplicate reports, (3) studies without the primary outcomes. Furthermore, the studies would be excluded if they were cross-over, quasi-RCTs, or observational studies.

The primary and secondary outcome measures

The primary outcomes was intubation rate, and the secondary outcomes included the incidences of bronchopulmonary dysplasia (BPD), retinopathy of prematurity(ROP), intraventricular hemorrhage(IVH), necrotizing enterocolitis(NEC), air leak and mortality.

Search strategies

A systematic literature search was conducted in Jan 1, 2021, using the methods of the Cochrane Collaboration for Systematic Reviews of Interventions. [20] We searched studies included in Medline, the Cochrane library, the Cochrane Controlled Trials Register, EMBASE, Chinese National Knowledge Infrastructure (CNKI), and Wanfang data Information Site. Furthermore, any ongoing or unpublished trials were also identified. We did not restrict studies according to language, and searched for studies written in any language from inception to Jan 1, 2021.

Following keywords were used: “noninvasive high-frequency oscillatory ventilation” or “nasal high-frequency oscillatory ventilation” or “noninvasive high-frequency oscillation ventilation” or “nasal high-frequency oscillation ventilation” and “preterm” or “infant” were used. Other neonatal experts were asked to search any unpublished or ongoing trials and two studies were identified. We applied the Cochrane sensitivity-maximizing and Cochrane sensitivity and precision-maximizing strategies as our special search strategies. [20]

Collection and assessment of the included and excluded studies

The obtained studies through the search strategies above were imported to an electronic bibliographic management program. We reviewed the titles and abstracts of the remaining articles and excluded those that were not related to our topic and those that did not meet the eligibility criteria. The full text versions were obtained for the relevant articles that could be included in the review.

The research strategies, article-extracting and data analysis were performed independently by three reviewers(Li Jie, Chen Long, Shi Yuan). Data analysis included study design, study interventions, number of subjects in each group, demographic characteristics, inclusion and exclusion criteria, primary and secondary outcomes, and variables used to assess study quality.

Statistical analyses

The Cochrane Risk of Bias tool[20] was applied to assess the methodological quality of the included studies. The statistical analyses were similar to the previous study. [21] Discrepancies among the three reviewers were resolved by discussion. Meta-analysis was performed using version 5.2 of Review Manager. To assess heterogeneity, 2 distribution and Higgins I² statistics were calculated to determine the percentage of total variation across studies resulting from heterogeneity. I² statistics approximating 25%, 50%, and 75% were considered low, medium, and high heterogeneity, respectively. The fixed-effects models were present, and the random-effects models were used whenever considerable heterogeneity was shown. For categorical data, the effect is expressed as the relative risk(RR), and for continuous data the effect is expressed as the weighted mean difference(MD) (95% confidence interval(CI)). Otherwise, to further assess effect of the individual study on the primary outcome, sensitivity or subgroup analysis would be performed after excluding the included studies with significant difference.

Results

Description of the included studies

Generally, fourteen randomized controlled studies were identified, of which ten were excluded for the following causes: one was the protocol[22] and one was the preliminary report[23] in Chinese of Zhu et al[17], three were compared after extubation, [24-26] three were randomized crossover studies,[13,27,28] one was compared between NHFOV and DuoPAP,[29] and one was compared between NHFOV and BP-CPAP as rescuing treatment of failure of NCPAP.[14] Finally, four eligible studies and 570 participants were included in the subsequent analysis. [17-19,30]（Fig.1）Tables 1-3 summarized the characteristics and quality assessments of these studies.

The primary and secondary outcomes

The meta-analysis indicated that NHFOV resulted in less intubation rate(RR:0.47; 95% CI:0.31-0.70, P=0.0002) as compared with NCPAP and heterogeneity was not found among the four trials in the fixed effects model (P=0.69, I²=0%) (Fig. 2). In sensitivity analysis, after excluding the study by Zhu et al. [17], the present study also indicated that NHFOV resulted in less intubation rate(RR:0.49; 95% CI:0.29-0.81, P=0.006) as compared with NCPAP and heterogeneity was not found among the other three trials in the fixed effects model (P=0.52, I²=0%)

Furthermore, the meta-analysis did not report significant differences in the incidence of BPD(RR:1.14; 95% CI:0.66-1.96, P=0.64), mortality (RR:1.00; 95% CI:0.44-2.25, P=0.99), IVH(RR:0.77; 95% CI:0.39-1.53, P=0.45), NEC(RR:1.19; 95% CI:0.52-2.69, P=0.68), ROP(RR:0.61; 95% CI:0.26-1.44, P=0.26), and air leak(RR:1.71; 95% CI:0.51-5.68, P=0.38) as compared with NCPAP, and heterogeneities were also not found among the four trials in the fixed effects model.(P=0.43, I²=0%)(P=0.70, I²=0%)(P=0.29, I²=20%)(P=0.21, I²=37%)(P=0.35, I²=0%)(P=0.54, I²=0%)(supplementary Fig. 3-8)

Discussion

In the present systematic review and meta-analysis, we aimed to evaluate whether NHFOV would reduce intubation rate as compared with NCPAP as the primary respiratory supporting modes in preterm infants with RDS. As a result, we found that NHFOV was superior to NCPAP in reducing the rate of intubation, and no heterogeneity was found. Similar result also appeared in sensitivity analysis after excluding one study with significant difference. And it was consistent with the subgroup analysis of the multicenter study by Shi et al. [18] The result suggests that NHFOV is a more reasonable selection to reduce the risk of intubation as compared with NCPAP in preterm neonate with RDS.

In the past twenty years, several studies have been enforced to compare the beneficial effects between NHFOV and NCPAP in preterm infants, and the results were encouraging. The study by van der Hoeven M et al. in 1998 demonstrated that, comparing with the NCPAP group, the PCO₂ level was lower in the NHFOV group in preterm and term neonates and the using criteria of NHFOV was deterioration on NCPAP. [31] A multicenter study also indicated the beneficial effects of NHFOV for preterm infants as a remedial measure after failing to other noninvasive modes in the mean number of apneas, bradycardias, or desaturations (3.2±0.4 vs. 1.2±0.3; P< 0.001), FiO2 (0.48±0.03 vs. 0.40±0.02; P<0.001) and the levels of PCO₂ (74±6 vs. 62 ±4; P= 0.025). [12] Otherwise, a study by Wang et al. in 2017 also indicated that, as a method of rescuing treatment after failure of other noninvasive respiratory supporting strategies, NHFOV significantly reduced the numbers of apnea(1.2±1.1 vs. 6.3±2.1, P<0.01) and SpO₂<0.85(1.1±1.2 vs. 4.3±1.5, P<0.01), the levels of PCO₂(43±8 vs. 56±10, P<0.01) and FiO₂(0.30±0.07 vs. 0.39±0.11, P<0.01). And it was consistent with the meta-analysis by Li et al., [32] in which NHFOV was demonstrated to increase the removal of carbon dioxide and reduce the risk of intubation and IV as compared with NCPAP/BP-CPAP in preterm infants. In contrast, NHFOV did not improve the oxygenation (0.42±0.12 vs. 0.40±0.10, P>0.05) and reduced the levels of PCO2 (49±8 vs. 48±7, P>0.05) as a prophylactically used mode in neonates after extubation, [33] and which was consistent with another randomized controlled cross-over study by Klotz D et al. [27] and the result did not show difference in levels of PCO₂(54.8±14.6 vs. 52.7±9.3, P=0.44; 49.0±8.1 vs. 47.7±9.5, P=0.55) between the NHFOV-NCPAP and NCPAP-NHFOV periods.

The first reasonable cause to explain the differences among the studies might be the diagnosis, and NHFOV might be more suitable in newborn infants with more severe respiratory distress. Previous studies were mainly enforced in the pre-neonatal acute respiratory distress syndrome(ARDS) era. In 2017, the first consensus definition for neonatal acute respiratory distress syndrome(ARDS) was provided, [34] and RDS and ARDS should be therefore diagnosed and compared independently. Our previous randomized controlled study also compared the beneficial effects between NHFOV with NCPAP on the need for IV in preterm infants with RDS and ARDS after extubation, and the results indicated that NHFOV did reduce significantly the need for endotracheal ventilation and levels of the PCO₂ as compared with NCPAP, especially in the subgroup of infants diagnosed with ARDS. [24] Among the trials included in the present study, the diagnosis of "the included criteria" were no completely consistent and ARDS was not included. The diagnosis of "the included criteria" was "RDS" in the studies by Shi et al. [18], Malakian et al. [19] and ranpour et al. [30]. But it was "moderate-severe RDS" in the study by Zhu et al. [17] And it was consistent with the previous reports by Mukerji et al. [12] and Wang et al., [33] in which NHFOV was successfully used in reduced PCO₂ and/or intubation rate as rescuing treatment after failure of other noninvasive ventilation. In contrast, there was similar intubation rate between NHFOV and NCPAP when the infants was stable on NCPAP after extubation. [27]

The second cause to explain the inconsistence might be the observation time of "need for mechanical ventilation". Among the trials included, the observation time of "need for mechanical ventilation" were different. The time of observation of "failure of NIPPV or NCPAP" was "7 days after birth" in the study by Shi et al. [18] and "within the first 72hr of life" in the studies by Malakian et al. [19] and Zhu et al. [17] and Iranpour et al. [30] did not limit the observation time of "failed nasal support".

The third cause might be the initial setting and subsequent adjustment of respiratory parameters of NHFOV. Among the four trials included, the parameters were different.(table 2) To further verify the results, a summary of all clinical studies referring to NHFOV in newborn infants was made and it was shown in table 4. [35-38] According to the summary, four reasons were accessible. Firstly, according to the report of Mukerji et al., [39] visible chest oscillation was not necessary because of elimination of CO₂ during NHFOV also occurring in the upper respiratory airway deadspace; Secondly, the mean tidal volume was higher with I:E at 50% than at 33% (2.4 ml vs. 1.4 ml; P < 0.001); [10] Thirdly, the setting of respiratory parameters should also be adjusted according to diagnosis and purpose, and an example was that Luca et al. suggested different parameters boundaries for NHFOV use in BPD-risk and postextubation newborn infants. [40] Last, the classifications of respiratory failure should be considered. Insufficient removal of carbon dioxide was usually one of the most important causes to induce higher incidence of intubation. Therefore, besides amplitude firstly up-regulated, frequency should be adjusted within the reported ranges to avoid hypercarbia. [11,39]

Besides efficacy, safety is another important focus when NHFOV was used. Similar to other noninvasive ventilation, NHFOV could also result in side effects. In the four included studies, Malakian et al. [19] reported that there were no differences in traumatization of nasal skin and mucosa, air leaks, IVH, feed intolerance and time to full feeds between the two groups. And there were no relevant reports in the studies by ranpour et al. [30] and Zhu et al. [17]. Shi et al. [18] indicated that the rate of thick secretions causing an airway obstruction was higher in the NHFOV group than in the NCPAP group(13.8% vs 5.3%; 95% CI of risk difference, 1.218 to 6.645; P = 0.018).

and it was consistent with the study by Fischer HS et al.. [16] Other than, air-trapping and NEC were shown in the study of Czernik Cet al. [41]

The major limitations of the present study: 1) The included studies were mainly performed in the pre-ARDS era, and no ARDS was included. 2) The initial respiratory parameters of NHFOV were different among the four trials. 3) The assessment for secondary outcomes were not enough in the small sample size. They might induce potential bias, including restricted application scope. These problems could be overcome in additional studies according to the present data. Recently, we have organized a multi-centers, randomized controlled trials regarding comparing NHFOV and NCPAP as the respiratory support modes after extubation in preterm infants (NCT03099694), and the results could give us more reasonable explanations.

In summary, among preterm infants with RDS, NHFOV was superior to NCPAP with respect to reducing the risk of intubation as the primary respiratory support strategies in the early life. Larger trials are needed to verify the beneficial effects.

Abbreviations

acute respiratory distress syndrome: ARDS; bronchopulmonary dysplasia: BPD; conventional mechanical ventilation: CMV; invasive ventilation: IV; intraventricular hemorrhage: IVH;  necrotizing enterocolitis: NEC; nasal continuous positive airway pressure: NCPAP; nasal intermittent positive pressure ventilation: NIPPV; nasal high frequency oscillatory ventilation: NHFOV; periventricular leukomalacia: PVL; retinopathy of prematurity: ROP; respiratory distress syndrome: RDS;

Declarations

Funding: The study was funded by Medical Science Study Program of Chongqing Hygiene and Health Commission(No. 2017MSXM018), Natural Science Foundation of Chongqing (cstc2020jcyj-msxmX0197), and "guan'ai" preterm Study Program of Renze Foundation of Beijing(K022).

Conflicts of interest: Shi Yuan have no conflicts of interest, and the other authors also have indicated they have no potential conflicts of interest to disclose.

Availability of data and material: Not applicable

Code availability: Not applicable

Author Contributions:

Li Jie: Dr Li accomplished the article-extracting and data analysis, drafted the initial manuscript and reviewed the manuscript.

Chen Long: Dr Chen conceptualized and designed the study, revised the initial manuscript.

Shi Yuan: Dr Shi conceptualized and designed the study, accomplished the article-extracting and data analysis, critically reviewed the manuscript for important intellectual content.

All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

Ethics approval: Not applicable

Consent to participate: Not applicable

Consent for publication: Not applicable

What's Known:

Nasal high-frequency oscillatory ventilation (NHFOV) has been described to be another advanced version of nasal continuous positive airway pressure (NCPAP). However, its beneficial effects among different studies as the primary modes in early life of preterm infants with respiratory distress syndrome(RDS) were inconsistent.

What is new:

Comparing with NCPAP, NHFOV decreases the risk of intubation as a primary respiratory supporting strategies in early life for preterm infants suffering from RDS.

Acknowledgments:

The study was funded by Medical Science Study Program of Chongqing Hygiene and Health Commission(No.2017MSXM018), Natural Science Foundation of Chongqing (cstc2020jcyj-msxmX0197) and "guan'ai" preterm Study Program of Renze Foundation of Beijing(K022).

References

1. Blencowe H, Cousens S, Oestergaard MZ, et al(2012) National, regional, and worldwide estimates of preterm birth rates in the year 2010 with time trends since 1990 for selected countries:a systematic analysis and implications. 379(9832): 2162-72. https://doi: 10.1016/S0140-6736(12)60820-4.
2. Stoll BJ, Hansen NI, Bell EF, et al (2010) Neonatal outcomes of extremely preterm infants from the NICHD Neonatal Research Network. Pediatrics. 126(3):443-56. https:// doi: 10.1542/peds.2009-2959.
3. Smith VC, Zupancic JA, McCormick MC, et al(2004) Rehospitalization in the first year of life among infants with bronchopulmonary dysplasia. J Pediatr.144(6):799-803. https:// doi: 10.1016/j.jpeds.2004.03.026.
4. Schmidt B, Asztalos EV, Roberts RS, et al(2003) Impact of bronchopulmonary dysplasia, brain injury, and severe retinopathy on the outcome of extremely low-birth-weight infants at 18 months: results from the trial of indomethacin prophylaxis in preterms.289(9):1124-9. https:// doi: 10.1001/jama.289.9.1124.
5. Kirpalani H, Millar D, Lemyre B, et al(2013) A trialcomparing noninvasive ventilation strategies in preterm infants. N Engl J Med. 369(7):611-20. https:// doi: 10.1056/NEJMoa1214533.
6. Chen L, Wang L, Li J, Wang N, Shi Y(2015) Noninvasive Ventilation for Preterm Twin Neonates with Respiratory Distress Syndrome: A Randomized Controlled Trial. Sci Rep.2015 Sep 24;5:14483. https://doi: 10.1038/srep14483.
7. Lemyre B, Davis PG, De Paoli AG, Kirpalani H(2017) Nasal intermittent positive pressure ventilation (NIPPV) versus nasal continuous positive airway pressure (NCPAP) for preterm neonates after extubation. Cochrane Database Syst Rev.2017 Feb 1;2:CD003212. https://doi: 10.1002/14651858.CD003212.pub3.
8. Lemyre B, Laughon M, Bose C, Davis PG(2016) Early nasal intermittent positive pressure ventilation (NIPPV) versus early nasal continuous positive airway pressure (NCPAP) for preterm infants. Cochrane Database Syst Rev.2016 Dec 15;12:CD005384. https://doi: 10.1002/14651858.CD005384.pub2.
9. De Luca D, Carnielli VP, Conti G, Piastra M(2010) Noninvasive high frequency oscillatory ventilation through nasal prongs: bench evaluation of efficacy and mechanics. Intensive Care Med. 36(12):2094-100. https:// doi: 10.1007/s00134-010-2054-7.
10. De Luca D, Piastra M, Pietrini D, Conti G(2012) Effect of amplitude and inspiratory time in a bench model of non-invasive HFOV through nasal prongs. Pediatr Pulmonol. 47(10):1012- https:// doi: 10.1002/ppul.22511.
11. De Luca D, Costa R, Visconti F, Piastra M, Conti G(2016) Oscillation transmission and volume delivery during face mask-delivered HFOV in infants: Bench and in vivo study. Pediatr Pulmonol. 51(7):705-12. https:// doi: 10.1002/ppul.23403.
12. Mukerji A,Singh B, Helou SE, et al(2018) Use of noninvasive high-frequency ventilation in the neonatal intensive care unit: a retrospective review. Am J Perinatol. 2015;30(2):171-6. https:// doi: 10.1055/s-0034-1381317.
13. Bottino R, Pontiggia F, Ricci C, et al(2018) Nasal high-frequency oscillatory ventilation and CO₂removal: A randomized controlled crossover trial. Pediatr Pulmonol. 53(9):1245-1251. https:// doi: 10.1002/ppul.24120.
14. Mukerji A, Sarmiento K, Lee B, Hassall K, Shah V(2017) Non-invasive high-frequency ventilation versus bi-phasic continuous positive airway pressure(BP-CPAP) following CPAP failure in infants <1250g: a pilot randomized controlled trial. J Perinatol. 37:49-53. https:// doi: 10.1038/jp.2016.172.
15. Hoehn T, Krause MF(2000) Effectiveelimination of carbon dioxide by nasopharyngeal high-frequency ventilation. Respir Med. 94(11):1132-4. https:// doi: 10.1053/rmed.2000.0889.
16. Fisher HS, Bohlin K, Buhrer C, et al(2015) Nasal high-frequency oscillation ventilation in neonates: a survey in five European Countries. Eur J Pediatr. 174:465-71. https:// doi: 10.1007/s00431-014-2419-y.
17. Zhu XW, Zhao JN, Tang SF, Yan J, Shi Y(2017) Noninvasive high-frequency oscillatory ventilationversus nasal continuous positive airway pressure in preterm infants with moderate-severe respiratory distress syndrome: A preliminary report. Pediatr Pulmonol. 52(8):1038-42. https:// doi: 10.1002/ppul.23755.
18. Shi Y, NHFOV group. Noninvasive high frequency oscillatory ventilation versus nasal continuous positive airway pressure in preterm infants with respiratory distress syndrome: A multi-center, prospective, randomized, controlled clinical superior trial. Neonatology.(accept)
19. Malakian A, Bashirnezhadkhabaz S, Aramesh MR, Dehdashtian M(2020) Noninvasive high-frequencyoscillatory ventilation versus nasal continuous positive airway pressure in preterm infants with respiratory distress syndrome: A randomized controlled trial. J Matern Fetal Neonatal Med. 33(15):2601-7. https:// doi: 10.1080/14767058.2018.1555810.
20. Moher D, Liberati A, Tetzlaff J, et al(2019) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 2009;6:e1000097. https:// doi: 10.1371/journal.pmed.1000097.
21. Long C, Li W, Wanwei L, Jie L, Yuan S(2016) Noninvasive Ventilation with Heliox for RespiratoryDistress Syndrome in Preterm Infant:A Systematic Review and Meta-Analysis. Can Respir J. 2016:9092871. https:// doi: 10.1155/2016/9092871.
22. Zhu XW, Shi Y, Shi LP, et al(2018) Non-invasive high-frequency oscillatory ventilation versus nasal continuous positive airway pressure in preterm infants with respiratory distress syndrome: Study protocolfor a multi-center prospective randomized controlled trial. 19(1):319. https:// doi: 10.1186/s13063-018-2673-9.
23. Zhu XW, Yan J, Ran Q, et al(2017) Noninvasive high-frequency oscillatory ventilation versus for respiratory distress syndrome in preterm infants: a preliminary report. Chin J Neonatol. 32:291-4.(In Chinese) https:// DOI: 10.3760/cma.j.issn.2096-2932.2017.04.012
24. Long Chen, Li Wang, Juan Ma, Zhichun Feng, Jie Li, Yuan Shi(2019) Nasal high-frequency oscillatory ventilation in preterm infants with respiratory distress syndrome(RDS) and acute respiratory distress syndrome(ARDS) after extubation: a Randomized Controlled Trial. Chest. 155(4):740-748. https:// doi: 10.1016/j.chest.2019.01.014.
25. Lou WB, Zhang WX(2017) Noninvasive high-frequency oscillatory ventilation versus nasal continuous positive airway pressure in premature infants with respiratory distress syndrome after weaning: A randomized controlled trial. Guangdong Med J. 38:2037-40. (In Chinese)
26. Fischer HS, Bührer C, Czernik C(2019) Hazards to avoid in future neonatal studies of nasal high-frequency oscillatory ventilation: lessons from an early terminated trial. BMC Res Notes.12(1):237. https:// doi: 10.1186/s13104-019-4268-2.
27. Klotz D, Schneider H, Schumann S, et al(2018) Non-invasive high-frequency oscillatory ventilation in preterm infants: a randomised controlled cross-over trial. Arch Dis Child Fetal Neonatal Ed. 103:1-5. https:// doi: 10.1136/archdischild-2017-313190.
28. Rüegger CM, Lorenz L, Kamlin COF, et al(2018) The Effects of Noninvasive High-Frequency OscillatoryVentilation on Desaturations and Bradycardia in Very Preterm Infants:A Randomized Crossover Trial. J Pediatr. 201:269-273.e2. https:// doi: 10.1016/j.jpeds.2018.05.029.
29. Lou WB, Zhang WX, Yuan L, Zhang B(2018) Comparative study of noninvasive high-frequency oscillatory ventilation and bilevel positive airway pressure ventilation for preterm infants with respiratory distress syndrome. Chinese Gen Prac. 21:1983–8.(In Chinese)
30. Iranpour R, Armanian AM, Abedi AR, Farajzadegan Z(2019) Nasal high-frequency ventilation (NHFV) versus nasal continuous positive airway pressure (NCPAP) as an initial therapy for respiratory distress syndrome (RDS) in preterm newborns. BMJ Pediatrics Open. 3:e000443. https://doi:10.1136/bmjpo-2019-000443.
31. van der Hoeven M, Brouwer E, Blanco CE(1998) Nasalhigh frequency ventilation in neonates with moderate respiratory insufficiency. Arch Dis Child Fetal Neonatal Ed. 79(1):F61-3. https:// doi: 10.1136/fn.79.1.f61.
32. Li J, Li X, Huang X, Zhang Z(2019) Noninvasive high-frequency oscillatory ventilationas respiratory support in preterm infants: a meta-analysis of randomized controlled trials. Respir Res. 20(1):58. https:// doi: 10.1186/s12931-019-1023-0.
33. Wang CH, Shi LP, Ma XL, et al(2017) Use of noninvasivehigh frequency oscillatory ventilation in very low birth weight infants. Zhonghua Er Ke Za Zhi. 55(3):177-181. https://doi: 10.3760/cma.j.issn.0578-1310.2017.03.003.
34. De LucaD, van Kaam AH, Tingay DG, et al(2017) The Montreux definition of neonatal ARDS: biological and clinical background behind the description of a new entity. Lancet Respir Med. 5(8):657-666. https:// doi: 10.1016/S2213-2600(17)30214-X.
35. Colaizy TT, Younis UM, Bell EF, Klein JM(2008) Nasalhigh-frequency ventilation for premature infants. Acta Paediatr. 97(11):1518-22. https:// doi: 10.1111/j.1651-2227.2008.00900.x.
36. Aktas S, Unal S, Aksu M, et al(2016) Nasal HFOV with Binasal Cannula Appears Effective and Feasiblein ELBW Newborns. J Trop Pediatr. 62(2):165-8. https:// doi: 10.1093/tropej/fmv088.
37. Thatrimontrichai A, Sirianansopa K, Janjindamai W, et al(2020) Comparison of Endotracheal Reintubationbetween Nasal High-Frequency Oscillationand Continuous Positive Airway Pressure in Neonates. Am J Perinatol. 37(4):409-14. https:// doi: 10.1055/s-0039-1679932.
38. Łoniewska B, Tousty J, Michalczyk B, et al(2019) The Use of NoninvasiveVentilation with High Frequency in Newborns-A Single-CenterExperience. Am J Perinatol. 36(13):1362-7. https:// doi: 10.1055/s-0038-1677471.
39. Mukerji A,Finelli M, Belik J(2013) Nasal high-frequency oscillation for lung carbon dioxide clearance in the newborn. 103(3):161-5. https:// doi: 10.1159/000345613.
40. De Luca D,Dell'Orto V(2016) Noninvasive high-frenquency oscillatory ventilation in neonates: review of physiology, biology and clinical data. Arch Dis Child Fetal Neonatal Ed. 101(6):F565-70. https:// doi: 10.1136/archdischild-2016-310664.
41. Czernik C,Schmalisch G, Bührer C, Proquitté H(2012) Weaning of neonates from mechanical ventilation by use of nasopharyngeal high-frequency oscillatory ventilation: a preliminary study. J Matern Fetal Neonatal Med. 25(4):374-8. https:// doi: 10.3109/14767058.2011.580401.

Tables

Table 1 The characteristics of included studies

NHFOV: nasal high frequency oscillation ventilation; NCPAP: nasal continuous positive airway pressure

Table 2: Details of included papers

NHFOV: nasal high frequency oscillation ventilation; NCPAP: nasal continuous positive airway pressure; "-": no data available;

Table 3: Bias assessment of included papers

table 4 the characteristics, initial settings for respiratory parameters and key results of the published clinical studies referring to NHFOV.

RDS, respiratory distress syndrome; TTN, transient tachypnea of newborn; NCPAP, nasal continuous positive airway pressure; RCT, randomized controlled trial; MAP: mean airway pressure;

NEC, necrotizing enterocolitis; NIV, noninvasive ventilation;