The NEU - CAP Trial

Rationale: Most infants establish effective gas exchange after birth independently with spontaneous breathing. Those that don't, receive breathing support non-invasively either through a face mask or invasively through endotracheal tube (ETT). Endotracheal ventilation is associated with lung injury in preterm infants. As a result, clinicians aim to support premature infants non-invasively and to only intubate those who don't respond adequately to mask positive pressure ventilation (PPV). It is a challenge for clinicians to judge how well infants are breathing and the effect of PPV during face mask breathing support. Current methods of monitoring provide indirect feedback that may be difficult to interpret. Exhaled carbon dioxide (CO₂) detectors that change colour in the presence of CO₂ are used to confirm ETT position. Detection of CO₂ during mask breathing support may offer a direct indication of gas exchange, which might allow for better assessment of spontaneous breathing and ventilation effectiveness.

Objective: To assess the effect of colorimetric CO₂ detector use during non-invasive ventilation, versus standard care, on the proportion of neonates receiving PPV after 5 minutes of life

Study design: This is a stepped-wedge cluster randomised trial, with randomisation occurring at the level of the participating hospital rather than the individual infant. This design is suitable for evaluating interventions with a potential learning effect and supports a structured implementation across study sites.

Study population: Infants receiving non-invasive breathing support in the first 10 minutes of life, born before 32 weeks of gestation.

Intervention: At the start of the study, all participating centres will continue their standard practice by providing non-invasive breathing support without using a CO₂ detector. As the study progresses, centres will switch one-by-one to using the colorimetric CO₂ detector during mask breathing support until all have switched. Once they have switched, centres will continue to use the CO₂ detector until the end of the study.

Main study parameter: The proportion of infants receiving PPV after 5 minutes of life.

Inclusion criteria

• Born before 32 weeks of gestation
• Received non-humidified face-mask support in the first 10 minutes of life
• Parental consent obtained

Exclusion criteria

• Congenital diaphragmatic hernia
• Tracheo-oesophageal fistula
• Cyanotic heart disease
• Surfactant protein deficiency
• Any other congenital abnormality or condition with an adverse effect on breathing, ventilation, or oxygenation. Many of the infants enrolled in the study will later be diagnosed with respiratory distress syndrome (RDS); this will not render them ineligible for inclusion.