Nasal CPAP or Intubation at Birth for Very Preterm Infants

COIN Trial · NEJM · 2008

The COIN Trial (Continuous Positive Airway Pressure or Intubation at Birth, Morley et al., *N Engl J Med* 2008) investigated whether early nasal continuous positive airway pressure (CPAP) applied in the delivery room could reduce death or bronchopulmonary dysplasia (BPD) in extremely preterm infants compared to routine early intubation and mechanical ventilation. **The Studied Regimen (The "COIN Protocol")** Infants breathing spontaneously at 5 minutes of age were randomized to: * **Nasal CPAP:** Initial delivery-room CPAP at 8 cm H₂O via nasal prongs, titrated between 5–8 cm H₂O in the NICU. Intubation and surfactant administration were reserved for predefined failure criteria (FiO₂ > 0.60, severe apnea, or persistent respiratory acidosis). * **Early Intubation:** Endotracheal intubation within 15 minutes of birth, early surfactant therapy, and ongoing conventional mechanical ventilation.

Primary Composite Outcome (Death or BPD):** No statistically significant difference between the CPAP and intubation groups at 36 weeks PMA (33.9% vs. 38.9%; OR: 0.80, 95% CI: 0.58–1.12; p = 0.19).

* **Mortality at 36 Weeks PMA:** Similar between groups (6.5% vs. 5.9%; OR: 1.11, 95% CI: 0.57–2.17; p = 0.75).

* **BPD at 36 Weeks PMA (Survivors):** Lower in the CPAP group, though not reaching statistical significance (33.9% vs. 39.1%; OR: 0.80, 95% CI: 0.57–1.12; p = 0.19). At 28 days of life, significantly fewer infants in the CPAP group required oxygen (53.9% vs. 64.8%; OR: 0.63, 95% CI: 0.46–0.88; p = 0.006).

* **Duration of Mechanical Ventilation:** Significantly reduced in the CPAP arm (median: 3 days vs. 4 days; p = 0.04), with fewer total days of assisted ventilation.

* **Avoidance of Intubation:** 46% of infants in the CPAP group never required endotracheal intubation or surfactant throughout their hospital stay.

* **Adverse Event (Pneumothorax):** Significantly higher incidence of pneumothorax in the CPAP group (9.1% vs. 3.0%; OR: 3.16, 95% CI: 1.41–7.07; p = 0.003).

* **Other Complications:** No significant differences in severe intraventricular hemorrhage (grade III/IV: 12.1% vs. 10.5%), cystic periventricular leukomalacia, patent ductus arteriosus, or necrotizing enterocolitis.

1. **High Initial Pressure Setting:** The protocol used a fixed starting CPAP level of 8 cm H₂O without early surfactant, which contributed significantly to the threefold increase in air leaks/pneumothoraces (particularly in the 25–26 week subgroup).

2. **Exclusion of the Sickest Infants:** Neonates who were apneic, severely depressed, or unable to sustain spontaneous respiration at 5 minutes were excluded, introducing potential selection bias toward more vigorous infants.

3. **Surfactant Delay:** Surfactant was not administered non-invasively (e.g., LISA/MIST); infants had to formally fail CPAP criteria before receiving salvage surfactant via standard intubation.

Early nasal CPAP started immediately in the delivery room is a viable, lung-protective alternative to routine prophylactic intubation in spontaneously breathing preterm infants (25–28 weeks), successfully avoiding mechanical ventilation in nearly half of the babies.

However, starting at a rigid 8 cm H₂O without early surfactant incurs a distinct risk of pneumothorax, reinforcing modern practices of initiating CPAP at 5–7 cm H₂O and adopting early non-invasive surfactant delivery strategies (e.g., LISA/MIST).