Fraction of Inspired Oxygen as a Predictor of CPAP Failure in Preterm Infants with Respiratory Distress Syndrome: A Prospective Multicenter Study1
Gulczyńska, E., Szczapa, T., Hożejowski, R., Borszewska-Kornacka, M. K., & Rutkowska, M. (2019). Fraction of Inspired Oxygen as a Predictor of CPAP Failure in Preterm Infants with Respiratory Distress Syndrome: A Prospective Multicenter Study. Neonatology, 116(2), 171–178.
Introduction
Treatment of respiratory distress syndrome (RDS) with early nasal continuous positive airway pressure (CPAP) is widespread for infants who do not require intubation during post-birth stabilisation. Early CPAP is recommended for those who are at risk of RDS, but do not require mechanical ventilation (MV) and early CPAP has the clinical benefit of the potential avoidance of invasive ventilation.
Infants who fail CPAP are at an increased risk of death, pneumothorax and bronchopulmonary dysplasia (BPD). This study therefore aimed to identify relevant prognostic factors and define the FiO2 as threshold indicative of likely CPAP failure.
Study design:
This was a prospective, multicentre cohort study conducted across 29 tertiary neonatal intensive care units (NICUs) from October 2016 to January 2018. It included preterm infants (<30 weeks gestation) who required CPAP within 15 minutes of birth and excluded those with significant congenital abnormalities. CPAP failure was defined as the need for MV within 72 hours. Univariate and multivariate logistic regression models analysed demographic, perinatal, and respiratory parameters, and receiver operating characteristic (ROC) analysis identified an FiO₂ threshold predictive of CPAP failure.
If surfactant was required, centres with limited experience in less invasive surfactant administration (LISA) were permitted to use the INSURE technique (intubation-surfactant-extubation). Use of the INSURE technique was not considered as CPAP failure as long as the infant was extubated within 30 minutes.
Adapted from Gulczyńska, et al 2019.
Results:
A total of 389 preterm infants were included in the analysis after five were excluded due to transfer or insufficient data. The mean gestational age was 28.2 weeks (±1.2 weeks), and the mean birth weight was 1,115 g. Most infants (83.5%) were delivered via Caesarean section, and 89.7% had received antenatal steroids.
Incidence of CPAP failure:
CPAP failure was observed in 27.8% (108/389) of the study population, with incidence varying by gestational age, from 50% at 23–24 weeks to 22.7% at 29 weeks.
Infants who experienced CPAP failure had lower gestational age (GA), birth weight, and five-minute Apgar scores compared with those who succeeded. They also required significantly higher FiO₂ levels and were more likely to have received exogenous surfactant (Table 1).
Predictors of CPAP failure:
CPAP failure was observed in 27.8% (108/389) of the study population, with incidence varying by GA, from 50% at 23–24 weeks to 22.7% at 29 weeks.
Univariate analysis identified gestational age, birth weight, and FiO₂ levels in the first and second hours of life as significant predictors of CPAP failure with the following considerations (Table 2):
- Each additional week of GA reduced the odds of failure by 19%
- Each 100 g increase in birth weight decreased the odds by 16%
- Higher FiO2 levels both in the first and second hour of life increased the odds for CPAP failure by 4.2% and 7.5%, respectively, per each percentage point of oxygen concentration
Multivariate analysis and FiO2 threshold:
In the final multivariate analysis, birth weight and FiO₂ during the second hour of life emerged as the strongest predictors of CPAP failure. ROC analysis indicated that an FiO₂ threshold of 0.29 in the second hour was most predictive, with a sensitivity of 73% and specificity of 57%. The area under the curve (AUC) for this model was 0.7, (Figure 1).
Complications associated with CPAP failure:
CPAP failure was associated with increased odds of unfavourable outcomes, including significantly higher rates of mortality (OR= 26.5; 95% CI: 7.8, 90 .1), an approximately 2- to 5-fold increase in the incidence of typical complications of prematurity, and respiratory complications encompassing moderate to severe BPD, as shown in Figure 2.
Conclusion:
FiO₂ in the second hour of life was identified as a significant predictor of CPAP failure in preterm infants with respiratory distress syndrome. An FiO2 threshold of 0.29 demonstrated the best discriminatory ability for predicting CPAP outcome.
CPAP failure was strongly associated with adverse outcomes, including a more than 20-fold increase in mortality and significantly higher rates of complications. These findings emphasise the importance of early identification and targeted management to optimise outcomes for preterm infants requiring respiratory support.
Never miss an update on new clinical summaries! Sign up to be notified when we publish comprehensive overviews on the latest neonatal topics, ensuring you stay informed with the newest insights.
Abbreviations
AUC, area under the curve; CPAP, continuous positive airway pressure; FiO₂, fraction of inspired oxygen; GA, gestational age; INSURE, intubation-surfactant-extubation; IQR, interquartile range; IVH, intraventricular haemorrhage; LISA, less invasive surfactant administration; MV, mechanical ventilation; NICU, neonatal intensive care unit; OR, odds ratio; PDA, patent ductus arteriosus; RDS, respiratory distress syndrome; ROC, receiver operating characteristic; SD, standard deviation.
References
- Gulczyńska E, et al. Fraction of Inspired Oxygen as a Predictor of CPAP Failure in Preterm Infants with Respiratory Distress Syndrome: A Prospective Multicenter Study. Neonatology. 2019;116(2):171–178.
IE-CUR-2500007 | April 2025
Adverse event reporting
For the UK: Adverse events should be reported. Reporting forms and information can be found at https://yellowcard.mhra.gov.uk/ or search for MHRA Yellow Card in the Google Play or Apple App Store. Adverse events should also be reported to Chiesi Limited on 0800 0092329 (UK) or PV.UK@Chiesi.com.
For Ireland: Adverse events should be reported to HPRA Pharmacovigilance – www.hpra.ie. Adverse events should also be reported to Chiesi Limited on 1800 817459 (IE) or PV.UK@Chiesi.com.