Win Tin, MD; for the Caffeine for Apnea of Prematurity (CAP) Trial Group IMPORTANCE Caffeine citrate therapy for apnea of prematurity reduces the rates of bronchopulmonary dysplasia, severe retinopathy, and neurodevelopmental disability at 18 months and may improve motor function at 5 years.OBJECTIVE To evaluate whether neonatal caffeine therapy is associated with improved functional outcomes 11 years later. DESIGN, SETTING, AND PARTICIPANTSA follow-up study was conducted at 14 academic hospitals in Canada, Australia, and the United Kingdom from May 7, 2011, to May 27, 2016, of English-or French-speaking children who had been enrolled in the randomized, placebo-controlled Caffeine for Apnea of Prematurity trial between October 11, 1999, and October 22, 2004. A total of 1202 children with birth weights of 500 to 1250 g were eligible for this study; 920 (76.5%) had adequate data for the main outcome.INTERVENTIONS Caffeine citrate or placebo until drug therapy for apnea of prematurity was no longer needed. MAIN OUTCOMES AND MEASURESFunctional impairment was a composite of poor academic performance (defined as at least 1 standard score greater than 2 SD below the mean on the Wide Range Achievement Test-4), motor impairment (defined as a percentile rank of Յ5 on the Movement Assessment Battery for Children-Second Edition), and behavior problems (defined as a Total Problem T score Ն2 SD above the mean on the Child Behavior Checklist).RESULTS Among the 920 children (444 females and 476 males; median age, 11.4 years [interquartile range, 11.1-11.8 years]), the combined rates of functional impairment were not significantly different between the 457 children assigned to receive caffeine compared with the 463 children assigned to receive placebo (145 [31.7%] vs 174 [37.6%]; adjusted odds ratio, 0.78; 95% CI, 0.59-1.02; P = .07). With all available data, including those from up to 24 Swedish trial participants, the rates of poor academic performance on 1 or more of 4 subtests (66 of 458 [14.4%] vs 61 of 462 [13.2%]; adjusted odds ratio, 1.11; 95% CI, 0.77-1.61; P = .58) and behavior problems (52 of 476 [10.9%] vs 40 of 481 [8.3%]; adjusted odds ratio, 1.32; 95% CI, 0.85-2.07; P = .22) were broadly similar between the group that received caffeine and the group that received placebo. However, caffeine therapy was associated with a reduced risk of motor impairment compared with placebo (90 of 457 [19.7%] vs 130 of 473 [27.5%]; adjusted odds ratio, 0.66; 95% CI, 0.48-0.90; P = .009). CONCLUSIONS AND RELEVANCECaffeine therapy for apnea of prematurity did not significantly reduce the combined rate of academic, motor, and behavioral impairments but was associated with a reduced risk of motor impairment in 11-year-old children with very low birth weight. At the doses used in this trial, neonatal caffeine therapy is effective and safe into middle school age.

Study Objectives: Although unattended ambulatory polysomnography (PSG) is frequently performed in adults, few studies have been performed in children. The objective of this study was to evaluate the feasibility of comprehensive, ambulatory PSG, including electroencephalography, in school-aged children in the home environment. Methods: A total of 201 children, born premature with birth weights of 500-1,250 grams, currently aged 5-12 years and living in Canada and Australia, underwent unattended ambulatory PSG. Results: PSG was initially technically satisfactory in 183 (91%) cases. Fourteen studies were satisfactory when repeated, resulting in an overall satisfactory rate of 197 (98%). Artifactfree signals were obtained for ≥ 75% of recording time in more than 92% of subjects, with the exception of nasal pressure, which was satisfactory for ≥ 75% of recording time in only 67% of subjects. However, thermistry signals were satisfactory for ≥ 75% of recording time in 92% of subjects, and some measure of airfl ow was present for ≥ 75% of recording time in 96% of subjects. Children slept very well, with a long total sleep time (534 ± 73 [mean ± SD] minutes), high sleep effi ciency (92% ± 5%), and low arousal index (9 ± 3/h). Parents and children reported a high rate of satisfaction with the study. Conclusions: This large, international study has shown that comprehensive, unattended, ambulatory PSG is feasible, technically adequate and well-tolerated in school-aged children when performed under research conditions. Further studies regarding the cost effi cacy of this approach, and generalizability of the fi ndings to a clinical population, are warranted. Keywords: polysomnography, sleep study, ambulatory, home, child Citation: Marcus CL, Traylor J, Biggs SN, Roberts RS, Nixon GM, Narang I, Bhattacharjee R, Davey MJ, Horne RS, Cheshire M, Gibbons KJ, Dix J, Asztalos E, Doyle LW, Opie GF, D'ilario J, Costantini L, Bradford R, Schmidt B. Feasibility of comprehensive, unattended ambulatory polysomnography in school-aged children. J Clin Sleep Med 2014;10(8):913-918.

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.

Neonatal caffeine therapy for apnea of prematurity improved visuomotor, visuoperceptual, and visuospatial abilities at age 11 years. General intelligence, attention, and behavior were not adversely affected by caffeine, which highlights the long-term safety of caffeine therapy for apnea of prematurity in very low birth weight neonates.

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