• Carole L Marcus, Lisa J Meltzer, Robin S Roberts, Joel Traylor, Joanne Dix, Judy D'ilario, Elizabeth Asztalos, Gillian Opie, Lex W Doyle, Sarah N Biggs, Gillian M Nixon, Indra Narang, Rakesh Bhattacharjee, Margot Davey, Rosemary S C Horne, Maureen Cheshire, Jeremy Gibbons, Lorrie Costantini, Ruth Bradford, Barbara Schmidt, and Caffeine for Apnea of Prematurity–Sleep Study.
• 1 Department of Pediatrics, Sleep Center, Children's Hospital of Philadelphia; University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania.
• Am. J. Respir. Crit. Care Med. 2014 Oct 1; 190 (7): 791-9.

RationaleApnea of prematurity is a common condition that is usually treated with caffeine, an adenosine receptor blocker that has powerful influences on the central nervous system. However, little is known about the long-term effects of caffeine on sleep in the developing brain.ObjectivesWe hypothesized that neonatal caffeine use resulted in long-term abnormalities in sleep architecture and breathing during sleep.MethodsA total of 201 ex-preterm children aged 5-12 years who participated as neonates in a double-blind, randomized, controlled clinical trial of caffeine versus placebo underwent actigraphy, polysomnography, and parental sleep questionnaires. Coprimary outcomes were total sleep time on actigraphy and apnea-hypopnea index on polysomnography.Measurements And Main ResultsThere were no significant differences in primary outcomes between the caffeine group and the placebo (adjusted mean difference of -6.7 [95% confidence interval (CI) = -15.3 to 2.0 min]; P = 0.13 for actigraphic total sleep time; and adjusted rate ratio [caffeine/placebo] for apnea-hypopnea index of 0.89 [95% CI = 0.55-1.43]; P = 0.63). Polysomnographic total recording time and total sleep time were longer in the caffeine group, but there was no difference in sleep efficiency between groups. The percentage of children with obstructive sleep apnea (8.2% of caffeine group versus 11.0% of placebo; P = 0.22) or elevated periodic limb movements of sleep (17.5% in caffeine group versus 11% in placebo group) was high, but did not differ significantly between groups.ConclusionsTherapeutic neonatal caffeine administration has no long-term effects on sleep duration or sleep apnea during childhood. Ex-preterm infants, regardless of caffeine status, are at risk for obstructive sleep apnea and periodic limb movements in later childhood.

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