Nasal continuous positive airway pressure does not reduce rate of death or bronchopulmonary dysplasia in preterm infants

Article Outline

• Morley CJ, Davis PG, Doyle LW, Brion LP, Hascoet JM, Carlin JB; COIN Trial Investigators. Nasal CPAP or intubation at birth for very preterm infants. N Engl J Med 2008;358:700-8
  • Question
  • Design
  • Setting
  • Participants
  • Intervention
  • Outcomes
  • Results
  • Conclusions
  • Comment
• Reference
• Copyright

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Morley CJ, Davis PG, Doyle LW, Brion LP, Hascoet JM, Carlin JB; COIN Trial Investigators. Nasal CPAP or intubation at birth for very preterm infants. N Engl J Med 2008;358:700-8 

Question 

In very preterm infants, does nasal continuous positive airway pressure (CPAP) reduce the rate of death or bronchopulmonary dysplasia, compared with intubation and ventilation?

Design 

Randomized trial.

Setting 

Perinatal centers in Australia, New Zealand, United States, Canada, and Europe.

Participants 

610 infants who were born at 25 to 28 weeks' gestation.

Intervention 

Infants were assigned to CPAP (starting at 8 cm H₂O) or intubation and ventilation 5 minutes after birth.

Outcomes 

The primary outcome was death or bronchopulmonary dysplasia (defined as the need for oxygen treatment at 36 weeks' gestation). Primary and secondary outcomes were assessed at 28 days of age, at 36 weeks' gestational age, and before discharge from the hospital.

Results 

At 36 weeks' gestational age, 33.9% of 307 infants who were assigned to receive CPAP had died or had bronchopulmonary dysplasia, as compared with 38.9% of 303 infants who were assigned to receive intubation (odds ratio favoring CPAP, 0.80; 95% CI, 0.58-1.12; P = .19). At 28 days, there was a lower risk of death or need for oxygen therapy in the CPAP group than in the intubation group (odds ratio, 0.63; 95% CI, 0.46-0.88; P = .006). There was little difference in overall mortality. In the CPAP group, 46% of infants were intubated during the first 5 days, and the use of surfactant was halved. The incidence of pneumothorax was 9% in the CPAP group, as compared with 3% in the intubation group (P < .001, number needed to harm [NNH] = 17). There were no other serious adverse events. The CPAP group underwent fewer days of ventilation.

Conclusions 

In infants born at 25 to 28 weeks' gestation, early nasal CPAP did not significantly reduce the rate of death or bronchopulmonary dysplasia, as compared with intubation. Although the CPAP group had more incidences of pneumothorax, fewer infants received oxygen at 28 days, and they had fewer days of ventilation.

Comment 

This is a large, multicenter randomized trial that has attempted to compare early CPAP with early intubation and ventilation. The major question at present is whether early CPAP is substantially equivalent to early surfactant, a well-established evidence-based intervention for the preterm infant. In understanding the results of this trial, it is important to note there were no protocol requirements for the administration of surfactant or caffeine for infants in either arm of the COIN trial, and no specified extubation criteria, because all centers followed local practice. In addition, the exclusion of infants of 24 weeks gestation removed the most at-risk infants, those who will most often fail CPAP treatment, who are likely to be the most informative. The results demonstrated that there was no difference in the groups for the primary outcome of death or bronchopulmonary dysplasia by using the need for oxygen at 36 weeks. There was a significant increase in the occurrence of pneumothorax in the CPAP group, most occurring within the first 2 days (9% versus 3%, P = .001). This study does not provide prospective evidence for the superiority of CPAP over early surfactant, because early surfactant was not mandated for the intubation group. The reported increase in air leaks may have been a result of the high level of CPAP used in this trial, or an intriguing possibility, caused by surfactant deficiency in the infants in the CPAP group. There was a significantly higher use of caffeine in the infants in the CPAP group, and, as the recent caffeine trial has demonstrated,¹ such treatment can significantly shorten the duration of ventilation. The debate about the superiority of CPAP compared with early surfactant will continue until the current ongoing larger trials are completed. At present, when considering early CPAP versus intubation with surfactant treatment, flip a coin!

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Reference 

1. Schmidt B, Roberts RS, Davis P, Doyle LW, Barrington KJ, Ohlsson A, et al. Caffeine for Apnea of Prematurity Trial Group Caffeine therapy for apnea of prematurity. N Engl J Med. 2006;354:2112–2121
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