Caffeine is the standard pharmacologic therapy for apnea of prematurity, with proven benefits in reducing bronchopulmonary dysplasia, facilitating extubation, and improving neurodevelopment. Emerging evidence suggests that early prophylactic caffeine may further reduce respiratory morbidity in preterm neonates . However, most previous studies classified ‘early’ caffeine as administration within 24–72 hours, an interval that overlaps substantially with therapeutic use, potentially diluting the true benefit of early prophylactic administration.

We propose a prospective, open-label, randomized controlled trial in preterm infants <32 weeks gestation to compare early prophylactic caffeine (within 2 h of birth) with therapeutic caffeine (administered peri-extubation or for apnea of prematurity). The primary outcome will be time to discontinuation of respiratory support.. Secondary outcomes will include time to discontinuation of initial invasive ventilation, echocardiographic parameters (left ventricular output, right ventricular output, superior vena cava flow, superior mesenteric artery doppler and anterior cerebral artery doppler at admission, 4 hours of life and 24-36 hours of life), cumulative duration of respiratory support during the hospital stay, bronchopulmonary dysplasia, hemodynamically significant patent ductus arteriosus, necrotizing enterocolitis, severe intraventricular haemorrhage, periventricular leukomalacia, retinopathy of prematurity, growth velocity, neonatal sepsis, use of post-natal steroids, duration of hospital stay and all cause mortality.

We plan to enroll 80 infants (40 per arm). We expect that early prophylactic caffeine will shorten the duration of respiratory support in preterm infants<32 weeks.