title: Long-term effects of caffeine therapy for apnea of prematurity on sleep at school age.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  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.
authors.affiliation: 1 Department of Pediatrics, Sleep Center, Children's Hospital of Philadelphia; University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania.
authors.forename: Carole L
authors.initials: CL
authors.lastname: Marcus
authors.forename: Lisa J
authors.initials: LJ
authors.lastname: Meltzer
authors.forename: Robin S
authors.initials: RS
authors.lastname: Roberts
authors.forename: Joel
authors.initials: J
authors.lastname: Traylor
authors.forename: Joanne
authors.initials: J
authors.lastname: Dix
authors.forename: Judy
authors.initials: J
authors.lastname: D'ilario
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Asztalos
authors.forename: Gillian
authors.initials: G
authors.lastname: Opie
authors.forename: Lex W
authors.initials: LW
authors.lastname: Doyle
authors.forename: Sarah N
authors.initials: SN
authors.lastname: Biggs
authors.forename: Gillian M
authors.initials: GM
authors.lastname: Nixon
authors.forename: Indra
authors.initials: I
authors.lastname: Narang
authors.forename: Rakesh
authors.initials: R
authors.lastname: Bhattacharjee
authors.forename: Margot
authors.initials: M
authors.lastname: Davey
authors.forename: Rosemary S C
authors.initials: RS
authors.lastname: Horne
authors.forename: Maureen
authors.initials: M
authors.lastname: Cheshire
authors.forename: Jeremy
authors.initials: J
authors.lastname: Gibbons
authors.forename: Lorrie
authors.initials: L
authors.lastname: Costantini
authors.forename: Ruth
authors.initials: R
authors.lastname: Bradford
authors.forename: Barbara
authors.initials: B
authors.lastname: Schmidt
mesh_terms: D056044:Actigraphy / Q000379:methods; D001049:Apnea / Q000188:drug therapy*; D002110:Caffeine / Q000009:adverse effects* / Q000627:therapeutic use*; D000697:Central Nervous System Stimulants / Q000009:adverse effects / Q000494:pharmacology*; D002648:Child; D002675:Child, Preschool; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000188:drug therapy*; D008297:Male; D010290:Parents; D017286:Polysomnography / Q000379:methods; D011446:Prospective Studies; D012890:Sleep / Q000187:drug effects*; D012893:Sleep Wake Disorders / Q000139:chemically induced*; D011795:Surveys and Questionnaires; D013995:Time
chemical_list: D000697:Central Nervous System Stimulants; D002110:Caffeine
keywords: apnea; methylxanthines; periodic limb movements during sleep