Long-term effects of therapeutic caffeine use for apnea of prematurity on sleep d

使用咖啡因治疗早产儿呼吸暂停对睡眠的长期影响

• 批准号: 7761600
• 负责人: CAROLE L MARCUS
• 金额: $ 41.73万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7761600
• 关键词: 6 year old; Acute; Adverse effects; Apnea; Behavior assessment; Behavioral; Birth; Brain; Breathing; Caffeine; Child; Childhood; Comorbidity; Enrollment; Infant; International; Long-Term Effects; Measures; Mediating; Needs Assessment; Neonatal; Neonatal Intensive Care Units; Neuraxis; Neurocognitive; Neurologic; Obstructive Sleep Apnea; Parents; Pattern; Pharmaceutical Preparations; Placebos; Polysomnography; Pregnancy; Premature Infant; Prevalence; Purinergic P1 Receptors; Questionnaires; Randomized; Research Infrastructure; Research Proposals; Risk; Sleep; Sleep Architecture; Sleep Disorders; Sleep disturbances; Sleeplessness; Theophylline; Therapeutic; Time; actigraphy; base; cohort; diaries; effective therapy; falls; follow-up; improved; indexing; methylxanthine; neonate; neurobehavioral; premature; public health relevance; sleep regulation

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: Methylxanthines are used often in the neonatal intensive care unit to treat premature infants with apnea of prematurity. However, the long-term consequences of these drugs are unknown. This study will determine whether neonatal methylxanthine treatment results in long-term perturbations in sleep, breathing during sleep, and hence, neurocognitive and behavioral abnormalities.

描述（由申请人提供）： 早产儿呼吸暂停是一种常见病症，通常用甲基黄嘌呤类药物治疗。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，人们对甲基黄嘌呤对大脑发育的长期影响知之甚少。特别是，尚不清楚甲基黄嘌呤是否会对睡眠结构和通气控制产生永久性的不利影响，从而导致失眠和阻塞性睡眠呼吸暂停综合征（OSAS）等睡眠障碍的患病率增加。早产儿神经行为异常的风险增加。这些神经系统合并症可能部分是通过甲基黄嘌呤暴露引起的睡眠障碍介导的。该研究计划将利用一组独特的早产儿、5-6 岁儿童，他们在出生时被随机分配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（咖啡因治疗早产儿呼吸暂停 [CAP] 试验）。进行这项研究具有时间上的紧迫性，因为 CAP 队列的随访正在进行中，并且神经行为评估需要在睡眠评估附近进行。总体假设是，甲基黄嘌呤在早产儿中的使用虽然在短期内有益，但会导致睡眠调节和睡眠期间呼吸的长期异常。在目标 1 中，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，我们将使用体动记录仪、睡眠日记和问卷来测量在新生儿期服用咖啡因或安慰剂的 5-6 岁早产儿的睡眠情况。我们假设，与对照组相比，摄入咖啡因的儿童睡眠时间会减少，入睡困难和保持睡眠困难的发生率会增加。在目标 2 中，我们将确定甲基黄嘌呤给药对儿童时期 OSAS 患病率的长期影响。具体来说，我们将使用动态多导睡眠图来表征在新生儿期接受咖啡因或安慰剂的 5-6 岁早产儿睡眠期间的呼吸特征。我们假设摄入咖啡因的儿童患 OSAS 的患病率会增加。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，我们将确定在新生儿期接受咖啡因或安慰剂的 5-6 岁早产儿的睡眠时间、OSAS 和神经行为测量（通过家长研究获得）之间的关系。我们假设睡眠中断和 OSAS 将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的长期后果，最终改善早产儿呼吸暂停的治疗。公共卫生相关性：新生儿重症监护室经常使用甲基黄嘌呤类药物来治疗患有早产儿呼吸暂停的早产儿。然而，这些药物的长期后果尚不清楚。这项研究将确定新生儿甲基黄嘌呤治疗是否会导致睡眠、睡眠期间呼吸的长期干扰，从而导致神经认知和行为异常。