Premature infants who require assisted ventilation or oxygen therapy are highly susceptible to bronchopulmonary dysplasia (BPD), a lung condition that Morley and colleagues defined as "the need for oxygen treatment at 36 weeks' gestational age." Despite the success of treatments such as antenatal steroids and surfactant, BPD continues to cause morbidity and death in very preterm infants.

An international randomized study was conducted to determine whether using continuous positive airway pressure (CPAP) rather than intubation shortly after birth would decrease the need for assisted ventilation and lower the rates of death and BPD in infants born between 25 and 28 weeks' gestation.

Infants who were breathing spontaneously at birth but needed some ongoing respiratory support were eligible for the trial. Infants were excluded if they had any condition (other than prematurity) that would predispose them to respiratory problems or if they had been intubated prior to randomization. The primary outcome was death or BPD and secondary outcomes included incidence and reason for intubation; need for oxygen therapy or treatment with methylxanthine, corticosteroids, and surfactant; incidences of air leaks and intracranial hemorrhages; duration of CPAP and ventilation; and length of hospital stay.

A total of 610 infants were randomly assigned to receive either nasal CPAP (n = 307) or intubation (n = 303). Infants were followed until death or discharge from the hospital. Parameters pertaining to apnea, arterial blood gases, metabolic acidosis, and oxygen concentration were set to define when infants assigned to CPAP would be intubated; intubation was needed in 46% of infants in the CPAP group within the first five days of life and in 12.7% after five days.

The utilization of nasal CPAP shortly after birth didn't have a statistically significant effect on the combined incidence of BPD or death when compared with intubation. However, at 28 days of age infants receiving CPAP had a significantly lower risk of death or need for oxygen therapy and fewer days on a ventilator (46% required a median of 6.6 hours on a ventilator within the first five days of life). Another statistically significant finding was that overall, infants on CPAP received surfactant half as often as intubated infants.

Twenty-eight infants on CPAP developed pneumothorax compared with nine in the intubation group, but this didn't increase the need for oxygen therapy or ventilatory support. The researchers were uncertain about the cause of the difference, especially considering the higher peak and mean airway pressures in the intubation group, but they did mention that studies have found lower rates of pneumothorax in infants treated with surfactant.

The authors listed a number of study limitations, including no blinding of treatment groups, the consent and enrollment process causing fewer infants with acute or serious antenatal problems to be included in the study population, the fact that most of the infant's mothers had received antenatal steroids, the exclusion of sick infants requiring intubation immediately after birth, and imprecise measurement of infrequent outcomes.

Lead author Morley told AJN, "The important point is that the [CPAP] group had general outcomes that were no worse than the infants ventilated from birth." When possible, he said, clinicians should start CPAP immediately at birth and then move on to intubation, ventilation, and surfactant if necessary. By doing this, nearly 50% fewer infants will require ventilation and surfactant.

KR