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.

项目摘要 脊柱裂是美国最常见的永久性致残性出生缺陷;脊髓脊膜膨出（MMC） 是最严重的形式。睡眠呼吸障碍（SDB）在受影响的儿童中很常见，是一个危险因素 在这个人群中突然死亡。对于MMC儿童，异常的睡眠生理可能是多因素的， 与脊柱缺损的水平、先天性和后天性脑干异常的存在有关， 肌肉骨骼因素和肺部异常然而，对SDB的系统评估并不是常规的。 胎儿手术闭合脊柱缺损是MMC治疗的一个重大进展。胎儿手术改善运动 发展，并可通过减少后脑疝减少脑室腹膜（VP）分流的需要， 但与出生后MMC修复相比，认知结果并未改善（平均Bayley-II精神 发育指数评分在30月龄时比正常对照组低约1 SD）和持久执行 功能缺陷在儿童后期很常见。胎儿MMC修复对睡眠病理生理的影响 仍然未知。与此同时，新出现的证据表明，对于其他健康的儿童，即使是轻微的 婴儿期SDB的症状，如父母报告的打鼾，确定了不良反应的长期风险。 神经行为后果，包括微妙的认知缺陷。因此，这项建议的前提是， SDB是MMC儿童异常认知结果的潜在可补救因素。 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与手术修复的时间无关。我们招募了20名患有MMC的新生儿， 多导睡眠图（5例胎儿修复和15例产后修复）。所有新生儿均患有SDB， 胎儿期和产后修复期之间的差异我们现在有一个独特的机会来利用 北美胎儿治疗网络（NAFTNet）的现有基础设施， 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中心的胎儿与出生后MMC修复是否影响新生儿SDB;目的2：定义 新生儿SDB、睡眠生理学客观指标、MMC手术时机和 MMC患者2岁时的神经发育结局;目的3：评估胎儿与术后 纳塔尔时MMC修复影响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， 可能对受影响儿童的健康和生活质量产生重大影响。这项研究将是第一次 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作为新标准治疗的一部分。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 医学和神经发育结果。