Caffeine for Apnea of Prematurity-Sleep (CAP-S) Study

Apnea of prematurity is a common condition that is usually treated with methylxanthines. Methylxanthines are adenosine receptor blockers that have powerful influences on the central nervous system. However, little is known about the long-term effects of methylxanthines on the developing brain. The Caffeine for Apnea of Prematurity-Sleep (CAP-S) Study is a sub-study of the main Caffeine for Apnea of Prematurity (CAP) trial, an international placebo-controlled randomized trial of methylxanthine therapy for apnea of prematurity. This sub-study is designed to take advantage of this cohort of ex-premature, 5-7 year old children who were randomized at birth to receive either caffeine or placebo, and are currently receiving detailed neurocognitive and behavioral assessments in the CAP trial.

The use of methylxanthines as therapy for apnea of prematurity may be a double-edged sword. Although widely-used, and efficacious for treatment of apnea of prematurity, long-term drug effects have not been rigorously studied. Neonatal methylxanthine therapy may have long-term impacts on sleep organization and ventilatory control. The CAP trial, funded by the Canadian Institutes of Health Research, was initiated due to the paucity of well-controlled data on the long-term effects of methylxanthines in preterm infants. The initial CAP trial was a multicenter, randomized, placebo-controlled trial of caffeine vs placebo as treatment for apnea of prematurity with follow-up to a corrected age of 18 months. 2,006 infants were enrolled. The CAP trial found that methylxanthines reduced the rates of bronchopulmonary dysplasia (BPD) and cerebral palsy (CP), and did not affect mortality. However, concerns remain regarding long-term sequelae of methylxanthine use. The Canadian Institutes of Health Research have therefore funded further follow-up of the entire CAP trial cohort to age 5 years, corrected for prematurity. The key objectives of this study are to examine the impact of methylxanthines on neurocognition and behavior. This ongoing parent study provides an opportunity to determine potential long-term effects of methylxanthines on sleep disorders, and to correlate these findings with daytime functioning. Our overall hypothesis is that methylxanthine use in preterm infants, while beneficial in the short term, results in longstanding abnormalities in the regulation of sleep, and breathing during sleep.