Long-term effects of caffeine therapy for apnea of prematurity on sleep at school age

Carole L Marcus, Lisa J Meltzer, Robin S Roberts, Joel Traylor, Joanne Dix, Judy D'ilario, Elizabeth Asztalos, Gillian F Opie, Lex W Doyle, Sarah Nichole Biggs, Gillian Michelle Nixon, Indra Narang, Rakesh Bhattacharjee, Margot J Davey, Rosemary Sylvia Claire Horne, Maureen Cheshire, K Jeremy Gibbons, Lorrie Costantini, Ruth Bradford, Barbara Schmidt

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59 Citations (Scopus)


Apnea 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. OBJECTIVES: We hypothesized that neonatal caffeine use resulted in long-term abnormalities in sleep architecture and breathing during sleep. METHODS: A 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 RESULTS: There 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. CONCLUSIONS: Therapeutic 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.
Original languageEnglish
Pages (from-to)791-799
Number of pages9
JournalAmerican Journal of Respiratory and Critical Care Medicine
Issue number7
Publication statusPublished - 2014

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