Sleep-disordered breathing in infants with myelomeningocele

脊髓脊膜膨出婴儿的睡眠呼吸障碍

• 批准号: 10532367
• 负责人: JOHN D BARKS
• 金额: $ 66.18万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-01-15 至 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10532367
• 关键词: 2 year old; Affect; Age; American; Apnea; Brain Stem; Caffeine; Child; Childhood; Clinical; Clinical Trials Design; Cognitive; Cognitive deficits; Congenital Abnormality; Consent; Creation of ventriculo-peritoneal shunt; Data; Defect; Development; Disease; Electroencephalography; Enrollment; Evaluation; Executive Dysfunction; Foundations; Functional disorder; Funding; Future; Gestational Age; Goals; Health; Hydrocephalus; Individual; Infant; Infant Development; Infrastructure; Intensive Care; Intervention; Intervention Studies; Longitudinal Studies; Lung; Measures; Medical; Medicine; Meningomyelocele; Michigan; Mission; Mothers; Motor; Musculoskeletal; Neonatal; Neonatal Screening; Newborn Infant; Observational Study; Operative Surgical Procedures; Outcome; Oxygen; Parents; Patients; Polysomnography; Population; Prevention; Procedures; Quality of life; Questionnaires; Reporting; Research Design; Research Personnel; Risk; Risk Factors; Seizures; Sleep; Sleep Apnea Syndromes; Snoring; Socioeconomic Status; Specialized Center; Spinal; Spinal Cord; Spinal Dysraphism; Stratification; Sudden Death; Symptoms; Translating; United States National Institutes of Health; Universities; Vertebral column; Work; clinical practice; clinically relevant; cognitive disability; cohort; disability; fetal; fetus surgery; follow-up; high risk; hindbrain; improved; indexing; infancy; innovation; malformation; mental development; multidisciplinary; neonate; neurobehavioral; non rapid eye movement; positive airway pressure; postnatal; prenatal therapy; programs; public health relevance; recruit; repaired; routine screening; screening; sex; sleep abnormalities; sleep behavior; sleep pattern; sleep physiology; standard of care; treatment strategy

PROJECT SUMMARY Spina bifida is the most common permanently disabling birth defect in the USA; myelomeningocele (MMC) is the most severe form. Sleep-disordered breathing (SDB) is common in affected children and is a risk factor for sudden death in this population. Abnormal sleep physiology is likely multifactorial for children with MMC, related to the level of spinal defect, presence of congenital and acquired brainstem abnormalities, musculoskeletal factors, and pulmonary abnormalities. Yet, systematic assessment for SDB is not routine. Fetal surgery to close the spinal defect is a major advance in MMC therapy. Fetal surgery improves motor development and can reduce the need for ventriculoperitoneal (VP) shunts by diminishing hindbrain herniation, but cognitive outcomes are not improved compared with post-natal MMC repair (mean Bayley-II mental development index scores ~1SD lower than normal controls at age 30 months) and persistent executive function deficits are common later in childhood. The effect of fetal MMC repair on sleep pathophysiology remains unknown. Meanwhile, emerging evidence suggests that for otherwise healthy children even mild symptoms of SDB during infancy, such as parent-reported snoring, identify long-term risk for adverse neurobehavioral consequences, including subtle cognitive deficits. Thus, the premise of this proposal is that SDB is a potentially remediable contributor to the abnormal cognitive outcomes for children with MMC. Innovative preliminary work by the investigators suggests that SDB is ubiquitous among newborns with MMC regardless of the timing of surgical repair. We recruited twenty newborns with MMC for neonatal polysomnography (5 fetal repair and 15 post-natal repair). All of these neonates had SDB, with no difference between those who received fetal vs. post-natal repair. We now have a unique opportunity to leverage the existing infrastructure of the North American Fetal Therapy Network (NAFTNet) for a multicenter observational study that will have direct impact on clinical practice through the following specific aims – Aim 1: Determine whether fetal vs. post-natal MMC repair at NAFTNet centers influences neonatal SDB; Aim 2: Define the association between neonatal SDB, objective measures of sleep physiology, timing of MMC surgery, and neurodevelopmental outcomes at age 2 years for patients with MMC; Aim 3: Assess whether fetal vs. post- natal MMC repair influences the risk for persistent SDB at age 2 years. Evaluation of sleep in neonates who require intensive care is an innovative, emerging opportunity with potential for major impact on health and quality of life for affected children. This study will be the first of its kind and could pave the way for a significant shift in clinical practice, to include routine screening of newborns with MMC for SDB as part of a new standard of care. Results of this work will inform future intervention studies designed to determine the most effective approach to treatment of SDB as a strategy to optimize long-term medical and neurodevelopmental outcomes.

项目概要 脊柱裂是美国最常见的永久性残疾出生缺陷；脊髓脊膜膨出 (MMC) 睡眠呼吸障碍 (SDB) 是最严重的一种，在受影响的儿童中很常见，也是一个危险因素。 对于患有 MMC 的儿童来说，睡眠生理异常可能是多种因素造成的。 与脊柱缺陷的程度、先天性和后天性脑干异常的存在有关， 然而，对 SDB 的系统评估并不常规。 胎儿手术闭合脊柱缺损是 MMC 治疗的重大进步 胎儿手术改善运动功能。 发育，并可以通过减少后脑疝来减少脑室腹膜（VP）分流的需要， 但与产后 MMC 修复相比，认知结果并未得到改善（平均 Bayley-II 心理 发育指数得分比 30 个月大时的正常对照低约 1SD）和持续的执行能力 功能缺陷在儿童后期很常见 胎儿 MMC 修复对睡眠病理生理学的影响。 与此同时，新出现的证据表明，对于其他健康的儿童来说，即使是轻度的。 婴儿期 SDB 症状，例如父母报告的打鼾，可确定不良的长期风险 神经行为后果，包括微妙的认知缺陷因此，该提议的前提是 SDB 是导致 MMC 儿童认知结果异常的潜在可补救因素。 研究人员的创新性初步工作表明，SDB 在新生儿中普遍存在 MMC 无论手术修复的时间如何，我们招募了 20 名患有 MMC 的新生儿进行新生儿治疗。 多导睡眠图（5 名胎儿修复和 15 名产后修复）所有这些新生儿均患有 SDB，没有差异。 我们现在有一个独特的机会来利用胎儿修复和产后修复之间的差异。 北美胎儿治疗网络 (NAFTNet) 的现有基础设施用于多中心观察 将通过以下具体目标对临床实践产生直接影响的研究 – 目标 1：确定 NAFTNet 中心的胎儿与产后 MMC 修复是否影响新生儿 SDB 目标 2：定义 新生儿 SDB、睡眠生理学客观测量、MMC 手术时机和 MMC 患者 2 岁时的神经发育结果；目标 3：评估胎儿期与出生后的情况 出生时 MMC 修复会影响 2 岁时持续性 SDB 的风险。 对需要重症监护的新生儿进行睡眠评估是一个创新的、新兴的机会 这项研究可能对受影响儿童的健康和生活质量产生重大影响，这将是此类研究中的第一项。 并可能为临床实践的重大转变铺平道路，包括对新生儿进行常规筛查 SDB 的 MMC 作为新护理标准的一部分，这项工作的结果将为未来的干预研究提供信息。 旨在确定治疗 SDB 的最有效方法，作为优化长期治疗的策略 医学和神经发育结果。