Long-Term Effects of Caffeine Therapy for Apnea of Prematurity on Sleep at School Age

Abstract

Rationale: 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 26.7 [95% confidence interval (CI) = 215.3 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.

Periodic limb movements and restless legs syndrome in children with a history of prematurity

“…CAPS showed no differences in sleep duration, obstructive sleep apnea syndrome (OSAS) or PLMI between the caffeine and placebo group. However, an increased percentage of these former preterm infants had OSAS and elevated PLMI 3 compared to normative data on otherwise healthy children. 4 …”

Sleep/Wake Patterns and Parental Perceptions of Sleep in Children Born Preterm

“…7 In brief, a subset of children enrolled in follow-up studies for the Caffeine for Apnea of Prematurity (CAP) trial 15,16 underwent 2-week actigraphy monitoring prior to a single night of comprehensive, ambulatory polysomnography. Polysomnography results are published elsewhere 7,17 and will not be reported here. Caregivers completed questionnaires relating to general sleep at the end of the 2-week actigraphy study.…”

“…6 In addition, children born preterm are at increased risk of sleep disorders such as obstructive sleep apnea (OSA) and periodic limb movements of sleep (PLMS). 7 If preterm children are found to have short sleep duration or irregular scheduling of bed and wake times, this may have an additive effect on daytime dysfunction.…”

Sleep disordered breathing in childhood

“…In contrast, animal studies suggested that neonatal caffeine has long-term detrimental effects on sleep and control of breathing. MARCUS et al [2] performed a multicentre international study (Caffeine for Apnea of Prematurity (CAP)) and evaluated 201 children of premature birth currently 5-12 years old. All children underwent unattended ambulatory polysomnography (PSG).…”