Sleep Disordered Breathing and Growth in Children: A Longitudinal Cohort Study

描述（由申请人提供）：我们将评估儿童生长衰竭（GF）与以打鼾、呼吸暂停和口呼吸为特征的睡眠呼吸障碍（SDB）之间的关系。腺扁桃体肥大是导致儿童SDB的主要因素。扁桃体切除术和腺样体切除术（T&A）治愈率为80%。作为一项专门针对SDB的干预措施，接受t&a的儿童表现出相应的益处，即追赶成长。来自转诊儿童的小型病例系列数据表明，SDB可能会增加GF的风险，但这从未在纵向、基于人群的研究中得到评估。我们将分析雅芳父母和儿童纵向研究（ALSPAC）中SDB和GF的数据，这是一项英国的前瞻性、基于人群的队列研究。ALSPAC是世界上最大、最清晰的儿童队列之一。ALSPAC的初步数据发现，在6个月大时打鼾的儿童在6- 42个月大时身高增长较小（p< 0.05）；在30-42月龄的儿童中，在18月龄时通过口呼吸的（p<.03）和在18月龄时报告有呼吸暂停的（p<.02）。据我们所知，我们的研究是第一个旨在检查SDB对长期不良增长的影响的研究。主要目的：（整个队列）1)表征儿童睡眠呼吸障碍（SDB）症状。我们将：a)测量SDB症状的患病率、严重程度和持续性；b)描述从婴儿期到青春期前SDB的自然和治疗史的趋势。2)确定SDB症状与生长之间的关系我们将评估：a) SDB症状的患病率、严重程度和持续性是否与GF相关；b)这种关联是由以下因素介导的还是独立于这些因素：早期生长模式、摄食习惯、能量摄入、T&A手术；家庭人口。次要目的：（队列子样本）3)确定SDB症状、饮食摄入、生长生物标志物和生长之间的关系我们将分析：a)血浆胰岛素样生长因子、瘦素水平、饮食摄入和SDB之间的关系；b)这些生物标志物与SDB及其相互作用对生长的影响。公共卫生相关性：ALSPAC提供了一个前所未有的机会来检查睡眠呼吸障碍（SDB）和整个儿童时期的生长，并评估因果关系的证据。自1992年以来，ALSPAC跟踪了13,000多名儿童的初始队列。经过验证的措施和多种数据来源（例如，检查、调查和健康记录）将允许合理有效的结论。该项目的国际多学科团队包括：生物统计学、内分泌学、流行病学、营养学、耳鼻喉科、儿科和肺病学/睡眠医学方面的专家。很少有儿科初级保健提供者筛查SDB， 50%的人不知道其与生长衰竭（GF）的潜在联系。无论是他们还是儿科GF的专科医生，在GF的鉴别诊断中都没有常规地包括上气道阻塞。在我们的纵向多变量分析中，如果SDB与GF有显著的时间相关性，那么对于GF患儿的筛查、转诊和治疗具有很强的临床实践意义。

DESCRIPTION (provided by applicant): We will evaluate the association between growth failures (GF) in children, and sleep disordered breathing (SDB) characterized by snoring, apnea, and mouth-breathing. Adenotonsillar hypertrophy is the primary factor leading to SDB in children. Tonsillectomy and adenoidectomy (T&A) is curative in 80% of cases. As an intervention specifically for SDB, children undergoing T&As show, as a corollary benefit, catch-up growth. Data from small, case series of referred children suggest that SDB may increase the risk of GF, but this has never been evaluated in a longitudinal, population-based study. We will analyze data on SDB and GF in the Avon Longitudinal Study of Parents and Children (ALSPAC), a prospective, population-based cohort study in the U.K. ALSPAC is amongst the largest, most well-delineated child cohorts in the world. Preliminary ALSPAC data find smaller height increases from 6- 42 months of age in children who snored at 6 months (p<.05), and; from 30-42 months of age in children who breathed through their mouth at 18 months (p<.03), and those with reported apnea at 18 months of age (p<.02). To our knowledge, ours is the first study designed to examine the impact of SDB upon poor growth over time. Primary Aims: (entire cohort) 1) To Characterize Sleep Disordered Breathing (SDB) Symptoms in Childhood We will: a) measure the prevalence, severity, and persistence of SDB symptoms, and; b) delineate trends in the natural and treatment history of SDB from infancy through pre-puberty. 2) To Determine the Association Between SDB Symptoms & Growth We will assess: a) whether the prevalence, severity, and persistence of SDB symptoms is associated with GF, and; b) whether such associations are mediated by or are independent of factors such as: early growth patterns, feeding habits, energy intake, T&A surgery, and; family demographics. Secondary Aim: (sub-sample of cohort) 3) To Determine Associations Between SDB Symptoms, Dietary Intake, Growth Biomarkers, & Growth We will analyze: a) the association between plasma insulin-like growth factors, leptin levels, dietary intake, and SDB, and; b) the effects of these biomarkers and SDB, and their interactions on growth. PUBLIC HEALTH RELEVANCE: ALSPAC provides an unprecedented opportunity to examine sleep disordered breathing (SDB) and growth throughout childhood, and evaluate evidence of causality. ALSPAC follows an inception cohort of 13,000+ children since 1992. Validated measures and multiple data sources (e.g., exams, surveys, and health records) will permit reasonably valid conclusions. The project's international multidisciplinary team includes expertise in: biostatistics, endocrinology, epidemiology, nutrition, otolaryngology, pediatrics, and pulmonology/sleep medicine. Few pediatric primary care providers screen for SDB, and 50% are unaware of its potential link to growth failure (GF). Neither they, nor sub-specialists in pediatric GF routinely include upper airway obstruction in their differential diagnosis of GF. If SDB has a significant temporal association with GF in our longitudinal, multivariable analysis, there are strong clinical practice implications for the screening, referral, and treatment of children with GF.