Long-term effects of caffeine therapy for apnea of prematurity on sleep disorders

早产儿呼吸暂停是一种常见的疾病，通常用甲基黄嘌呤治疗。甲基黄嘌呤是 腺苷受体阻滞剂，对中枢神经系统有强大的影响。然而， 甲基黄嘌呤对大脑发育的长期影响。尤其是， 甲基黄嘌呤是否对睡眠结构和睡眠控制具有永久性的不利影响， 导致睡眠障碍如失眠和阻塞性睡眠呼吸暂停的患病率增加 综合征（OSAS）。早产儿的神经行为风险增加 异常这些神经系统合并症可能部分通过睡眠介导 甲基黄嘌呤暴露可能导致的紊乱。这项研究计划将利用一个 一个独特的队列，5-6岁的早产儿，出生时随机接受咖啡因或 安慰剂，目前正在接受详细的神经认知和行为评估（咖啡因， 早产儿呼吸暂停[CAP]试验）。进行这项研究有一个基于时间的紧迫性，作为对 CAP队列研究正在进行中，需要在接近CAP队列的地方进行神经行为评估。 睡眠评估总的假设是，甲基黄嘌呤用于早产儿，而有益于 短期内，导致睡眠调节和睡眠期间呼吸的长期异常。在 目的1，我们将确定甲基黄嘌呤给药对睡眠/觉醒模式的长期影响。 具体来说，我们将使用活动记录仪、睡眠日记和问卷调查来测量早产儿5-6岁的睡眠情况。 在新生儿期接受咖啡因或安慰剂的老年儿童。我们假设， 接受咖啡因会减少睡眠时间，增加入睡困难的患病率， 与对照组相比，在目标2中，我们将确定甲基黄嘌呤的长期影响 在儿童时期的OSAS的患病率管理。具体而言，我们将使用门诊 多导睡眠描记术用于描述5-6岁早产儿睡眠期间的呼吸， 咖啡因或安慰剂在新生儿期。我们假设接受咖啡因的儿童会有一个 OSAS患病率增加。在目标3中，我们将确定睡眠中断、OSAS和 甲基黄嘌呤给药对早产儿神经认知和行为异常的影响 具体来说，我们将确定睡眠时间，阻塞性睡眠呼吸暂停综合征和神经行为指标之间的关系 （通过父母研究获得）在接受咖啡因或 在新生儿期给予安慰剂。我们假设睡眠中断和阻塞性睡眠呼吸暂停综合征会导致 神经认知和行为异常这些研究将有助于确定 新生儿甲基黄嘌呤治疗，最终导致早产儿呼吸暂停的改善管理。

Apnea of prematurity is a common condition that is usually treated with methylxanthines. Methylxanthines are adenosine receptor blockers that have powerful influences on the central nervous system. However, little is known about the long-term effects of methylxanthines on the developing brain. In particular, it is not known whether methylxanthines have permanent adverse effects on sleep architecture and ventilatory control, resulting in an increased prevalence of sleep disorders such as insomnia and the obstructive sleep apnea syndrome (OSAS). Children who were born prematurely are at increased risk for neurobehavioral abnormalities. It is possible that these neurologic comorbidities are mediated, in part, through sleep disturbances that may result from methylxanthine exposure. This research proposal will take advantage of a unique cohort of ex-premature, 5-6 year old children who were randomized at birth to receive either caffeine or placebo, and are currently receiving detailed neurocognitive and behavioral assessments (the Caffeine for Apnea of Prematurity [CAP] trial). There is a time-based urgency to performing this study, as follow-up of the CAP cohort is in progress, and neurobehavioral assessments need to be performed in close proximity to the sleep assessments. The overall hypothesis is that methylxanthine use in preterm infants, while beneficial in the short term, results in longstanding abnormalities in the regulation of sleep, and breathing during sleep. In Aim 1, we will determine the long-term effects of methylxanthine administration on sleep/wake patterns. Specifically, we will use actigraphy, sleep diaries and questionnaires to measure sleep in ex-premature 5-6 year old children who received either caffeine or placebo during the neonatal period. We hypothesize that children who received caffeine will have decreased sleep time, and increased prevalence of difficulties falling asleep and staying asleep, compared to controls. In Aim 2, we will determine the long-term effects of methylxanthine administration on the prevalence of OSAS during childhood. Specifically, we will use ambulatory polysomnography to characterize breathing during sleep in ex-premature 5-6 year old children who received either caffeine or placebo during the neonatal period. We hypothesize that children who received caffeine will have an increased prevalence of OSAS. In Aim 3, we will determine the contribution of sleep disruption, OSAS and methylxanthine administration to neurocognitive and behavioral abnormalities in ex-premature children. Specifically, we will determine the relationship between sleep time, OSAS and neurobehavioral measures (being obtained through the parent study) in ex-premature 5-6 year old children who received either caffeine or placebo during the neonatal period. We hypothesize that sleep disruption and OSAS will contribute to neurocognitive and behavioral abnormalities. These studies will help determine the long-term consequences of neonatal methylxanthine therapy, ultimately resulting in improved management of apnea of prematurity.