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

Marcus et al, Am J Respir Crit Care Med.  2014

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 -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.