Download PDF
Am J Perinatol
DOI: 10.1055/a-2624-5642
Original Article

The Predictors and Outcomes of Early Noninvasive Positive Pressure Ventilation Failure in Very Preterm Infants: A Prospective Study

Mustafa Senol Akin 
1   Department of Neonatology, Ankara Bilkent City Hospital, Ankara, Türkiye
,
Fatma Nur Sari 
2   Department of Neonatology, Ankara Bilkent City Hospital, University of Health Sciences, Ankara, Türkiye
,
Aslihan Kose Cetinkaya 
1   Department of Neonatology, Ankara Bilkent City Hospital, Ankara, Türkiye
,
Ismail Cagri Acikgoz 
1   Department of Neonatology, Ankara Bilkent City Hospital, Ankara, Türkiye
,
Evrim Alyamac Dizdar 
2   Department of Neonatology, Ankara Bilkent City Hospital, University of Health Sciences, Ankara, Türkiye
› Author Affiliations
Funding None.
› Further Information
Also available at
   Permissions and Reprints

Abstract

Objective

Limited data exist on predicting nasal intermittent positive pressure ventilation (NIPPV) failure in very preterm infants. This study aimed to identify factors predicting NIPPV failure, focusing on the fraction of inspired oxygen (FiO2), and evaluating associated outcomes.

Study Design

This prospective observational study included infants with gestational ages between 230/7 and 316/7 weeks, who were managed with NIPPV as the initial respiratory support. Infants were categorized as either successfully managed with NIPPV (NIPPV-S) or failed and required intubation within the first 72 hours of life (NIPPV-F). Predictors of NIPPV failure and clinical outcomes were evaluated. ROC curve analysis was used to determine FiO2 thresholds in the first and second hours of life. Demographic, perinatal, and respiratory parameters were analyzed using univariate and multivariate logistic regression models.

Results

Of the 397 infants, 121 (30.5%) failed NIPPV and required intubation. Multivariate analysis revealed that FiO2 in the first hour, FiO2 in the second hour, and mean airway pressure were independent predictors of NIPPV failure. The optimal FiO2 threshold was 0.32 (sensitivity, 79% and specificity, 50%) for the first hour and 0.31 (sensitivity, 75% and specificity, 55%) for the second hour of life. NIPPV failure was associated with an increased risk of pneumothorax (adjusted odds ratio [aOR]: 16.83; 95% confidence interval [CI]: 2.05–138.45; p < 0.001), BPD (aOR: 2.61; 95% CI: 1.47–4.62; p < 0.001), and mortality (aOR: 2.37; 95% CI: 1.32–4.23; p < 0.001).

Conclusion

FiO2 is a valuable predictor of NIPPV success in the early hours of life. NIPPV failure, predicted by a FiO2 exceeding 0.30 within the first 2 hours of life, is associated with adverse neonatal outcomes.

Key Points

  • FiO2 > 0.30 in first 2 hours predicts NIPPV failure in very preterm infants.

  • Early NIPPV failure is linked to increased risks of BPD, pneumothorax, and death.

  • FiO2 and MAP are independent predictors of NIPPV failure.

Keywords

FiO2 threshold - noninvasive ventilation - preterm infant

Ethical Approval

This study was approved by the Institutional Review Board of our tertiary center. (Ankara Bilkent City Hospital Ethics Committee number 1, ethics approval number E1–20–1250).


Clinical Trial

This study is registered with ClinicalTrial.gov (identifier: NCT05260424; https://clinicaltrials.gov/study/NCT05260424 ).


Patient Consent

Written informed consent was obtained from all the participants included in this study, and no identifying information from any participant was included.


Authors' Contributions

M.S.A. and F.N.S. were responsible for the data collection and analysis. M.S.A. wrote the manuscript, performed the planning of the method, and is responsible for the overall content (as a guarantor). F.N.S. reviewed and revised the manuscript accordingly. I.C.A. recorded the data and E.A.D. and A.K.C. performed statistical analysis of the data.




Publication History

Received: 12 February 2025

Accepted: 29 May 2025

Article published online:
16 June 2025

© 2025. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 

  • References

  • 1 Dumpa V, Bhandari V. Non-invasive ventilatory strategies to decrease bronchopulmonary dysplasia—where are we in 2021?. Children (Basel) 2021; 8 (02) 132
    PubMedSearch in Google Scholar
  • 2 Walsh MC, Morris BH, Wrage LA. et al; National Institutes of Child Health and Human Development Neonatal Research Network. Extremely low birthweight neonates with protracted ventilation: mortality and 18-month neurodevelopmental outcomes. J Pediatr 2005; 146 (06) 798-804
    CrossrefPubMedSearch in Google Scholar
  • 3 Ho JJ, Subramaniam P, Davis PG. Continuous positive airway pressure (CPAP) for respiratory distress in preterm infants. Cochrane Database Syst Rev 2020; 10 (10) CD002271
    PubMedSearch in Google Scholar
  • 4 Subramaniam P, Ho JJ, Davis PG. Prophylactic nasal continuous positive airway pressure for preventing morbidity and mortality in very preterm infants. Cochrane Database Syst Rev 2016; 6 (06) CD001243
    PubMedSearch in Google Scholar
  • 5 Owen LS, Manley BJ, Davis PG, Doyle LW. The evolution of modern respiratory care for preterm infants. Lancet 2017; 389 (10079): 1649-1659
    CrossrefPubMedSearch in Google Scholar
  • 6 Dargaville PA, Gerber A, Johansson S. et al; Australian and New Zealand Neonatal Network. Incidence and outcome of CPAP failure in preterm infants. Pediatrics 2016; 138 (01) e20153985
    CrossrefPubMedSearch in Google Scholar
  • 7 Lemyre B, Deguise M-O, Benson P, Kirpalani H, Ekhaguere OA, Davis PG. Early nasal intermittent positive pressure ventilation (NIPPV) versus early nasal continuous positive airway pressure (NCPAP) for preterm infants. Cochrane Database Syst Rev 2023; 7 (07) CD005384
    PubMedSearch in Google Scholar
  • 8 De Jaegere AP, van der Lee JH, Canté C, van Kaam AH. Early prediction of nasal continuous positive airway pressure failure in preterm infants less than 30 weeks gestation. Acta Paediatr 2012; 101 (04) 374-379
    CrossrefPubMedSearch in Google Scholar
  • 9 Fuchs H, Lindner W, Leiprecht A, Mendler MR, Hummler HD. Predictors of early nasal CPAP failure and effects of various intubation criteria on the rate of mechanical ventilation in preterm infants of <29 weeks gestational age. Arch Dis Child Fetal Neonatal Ed 2011; 96 (05) F343-F347
    CrossrefPubMedSearch in Google Scholar
  • 10 Dargaville PA, Aiyappan A, De Paoli AG. et al. Continuous positive airway pressure failure in preterm infants: incidence, predictors and consequences. Neonatology 2013; 104 (01) 8-14
    CrossrefPubMedSearch in Google Scholar
  • 11 Morley CJ, Davis PG, Doyle LW, Brion LP, Hascoet J-M, Carlin JB. COIN Trial Investigators. Nasal CPAP or intubation at birth for very preterm infants. N Engl J Med 2008; 358 (07) 700-708
    CrossrefPubMedSearch in Google Scholar
  • 12 Sandri F, Plavka R, Ancora G. et al; CURPAP Study Group. Prophylactic or early selective surfactant combined with nCPAP in very preterm infants. Pediatrics 2010; 125 (06) e1402-e1409
    CrossrefPubMedSearch in Google Scholar
  • 13 Roberts CT, Owen LS, Frøisland DH, Doyle LW, Davis PG, Manley BJ. Predictors and outcomes of early intubation in infants born at 28–36 weeks of gestation receiving noninvasive respiratory support. J Pediatr 2020; 216: 109-116.e1
    PubMedSearch in Google Scholar
  • 14 Handoka NM, Azzam M, Gobarah A. Predictors of early synchronized non-invasive ventilation failure for infants < 32 weeks of gestational age with respiratory distress syndrome. Arch Med Sci 2019; 15 (03) 680-687
    PubMedSearch in Google Scholar
  • 15 Textbook of Neonatal Resuscitation. Weiner GM, Zaichkin J. editors: American Academy of Pediatrics; 01 Jun 2021
    Search in Google Scholar
  • 16 Özkan H, Erdeve Ö, Kutman HGK. Turkish Neonatal Society guideline on the management of respiratory distress syndrome and surfactant treatment. Turk Pediatri Ars 2018; 53 (Suppl. 01) S45-S54
    PubMedSearch in Google Scholar
  • 17 Papile L-A, Burstein J, Burstein R, Koffler H. Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weights less than 1,500 gm. J Pediatr 1978; 92 (04) 529-534
    CrossrefPubMedSearch in Google Scholar
  • 18 Bell MJ, Ternberg JL, Feigin RD. et al. Neonatal necrotizing enterocolitis. Therapeutic decisions based upon clinical staging. Ann Surg 1978; 187 (01) 1-7
    CrossrefPubMedSearch in Google Scholar
  • 19 Jobe AH, Bancalari E. Bronchopulmonary dysplasia. Am J Respir Crit Care Med 2001; 163 (07) 1723-1729
    CrossrefPubMedSearch in Google Scholar
  • 20 Owen LS, Morley CJ, Davis PG. Pressure variation during ventilator generated nasal intermittent positive pressure ventilation in preterm infants. Arch Dis Child Fetal Neonatal Ed 2010; 95 (05) F359-F364
    PubMedSearch in Google Scholar
  • 21 Kakkilaya V, Wagner S, Mangona KLM. et al. Early predictors of continuous positive airway pressure failure in preterm neonates. J Perinatol 2019; 39 (08) 1081-1088
    CrossrefPubMedSearch in Google Scholar
  • 22 Kugelman A, Feferkorn I, Riskin A, Chistyakov I, Kaufman B, Bader D. Nasal intermittent mandatory ventilation versus nasal continuous positive airway pressure for respiratory distress syndrome: a randomized, controlled, prospective study. J Pediatr 2007; 150 (05) 521-526 , 526.e1
    CrossrefPubMedSearch in Google Scholar
  • 23 Buzzella B, Claure N, D'Ugard C, Bancalari E. A randomized controlled trial of two nasal continuous positive airway pressure levels after extubation in preterm infants. J Pediatr 2014; 164 (01) 46-51
    CrossrefPubMedSearch in Google Scholar
  • 24 Kidman AM, Manley BJ, Boland RA. et al. Higher versus lower nasal continuous positive airway pressure for extubation of extremely preterm infants in Australia (ÉCLAT): a multicentre, randomised, superiority trial. Lancet Child Adolesc Health 2023; 7 (12) 844-851
    CrossrefPubMedSearch in Google Scholar
  • 25 Dell'Orto V, Nobile S, Correani A. et al. Early nasal continuous positive airway pressure failure prediction in preterm infants less than 32 weeks gestational age suffering from respiratory distress syndrome. Pediatr Pulmonol 2021; 56 (12) 3879-3886
    CrossrefPubMedSearch in Google Scholar
  • 26 Rocha G, Flôr-de-Lima F, Proença E. et al. Failure of early nasal continuous positive airway pressure in preterm infants of 26 to 30 weeks gestation. J Perinatol 2013; 33 (04) 297-301
    CrossrefPubMedSearch in Google Scholar
  • 27 Gulczyńska E, Szczapa T, Hożejowski R, Borszewska-Kornacka MK, Rutkowska M. Fraction of inspired oxygen as a predictor of CPAP failure in preterm infants with respiratory distress syndrome: a prospective multicenter study. Neonatology 2019; 116 (02) 171-178
    PubMedSearch in Google Scholar