Children with Hypoglycemia and their Later Development (the CHYLD Study)

描述（由申请人提供）：低血糖是新生儿最常见的代谢紊乱，也是唯一已知的新生儿脑损伤的常见可预防原因。然而，诊断和治疗的最佳方法仍不清楚。一个主要的挑战是，不同的婴儿发生脑损伤时的血糖浓度可能不同，而且不知道在脑损伤发生之前，低血糖浓度必须达到多低、多频繁、持续多久。包括NICHD1在内，一直有人呼吁对儿童进行大规模的随访研究，在新生儿时期测量血糖浓度，并涵盖足够广泛的范围，以确定血糖浓度与后来结局之间的关系。本提案就是要进行这样的研究。我们的假设是，儿童早期的发育表现与出生后第一周低糖浓度的严重程度、持续时间和频率有关。具体的目的是确定：1。出生后第一周记录的低糖浓度的严重程度、持续时间和频率是否与2岁和4.5岁时的临床和发育结局有关。2. 这些关系是否在具有不同风险因素或围产期史的婴儿中有所不同。3. 在不同的婴儿群体中，葡萄糖浓度为“低”提供了最好的歧视性定义，从而可能为干预提供一个基于证据的阈值。一个小于500个足月和晚期早产儿（e35周）的队列正在被招募。所有人都有新生儿低血糖的危险，并根据目前的临床指南进行管理。所有婴儿在出生后至少48小时至7天内都要进行间质血糖监测。这些监测仪的数据不用于临床管理，但确实提供了关于低血糖浓度的严重程度、持续时间和频率的有价值的信息。大约40%的婴儿出现低血糖，临床定义为血糖浓度<2.6mM，因此需要治疗。然而，另有20-30%的患者出现间质葡萄糖浓度<2.6mM的发作，但临床未检测到，因此未进行治疗。父母同意的孩子将在2岁和4.5岁时接受评估。评估将包括对生长、神经功能、视觉、认知和语言发展、记忆、执行功能、一般健康和家庭环境的标准化测量。数据分析将包括多变量建模，以评估新生儿血糖浓度与发育结局之间的关系，并适当调整围产期事件和潜在的产后家庭和环境影响。结果将在短期内为临床实践提供急需的证据基础，同时也为设计适当干预措施的随机试验提供关键证据基础。

DESCRIPTION (provided by applicant): Hypoglycemia is the most common metabolic disorder of the newborn, and the only known common preventable cause of brain damage in newborn babies. However, the best approach to diagnosis and management remains unclear. One major challenge is that the blood glucose concentration at which brain damage is incurred may differ in different babies, and it is not known how low, how often, or for how long low blood glucose concentrations must occur before brain damage occurs. There have been calls, including from the NICHD1, for large follow-up studies of children in whom glucose concentrations were measured in the newborn period and encompassed a range wide enough to determine relationships between glucose concentrations and later outcome. This proposal is to conduct just such a study. Our hypothesis is that developmental performance in early childhood is related to the severity, duration and frequency of low glucose concentrations in the first week after birth. The specific aims are to determine: 1. Whether the severity, duration and frequency of low glucose concentrations recorded in the first week after birth are related to clinical and developmental outcomes at 2 and 4.5 years of age. 2. Whether these relationships differ in babies with different risk factors or perinatal histories. 3. What glucose concentrations provide the best discriminatory definition for "low" in relation to these outcomes in different groups of babies, and thus may provide an evidence-based threshold for intervention. A cohort of <500 term and late preterm babies (e35 weeks) is being recruited. All are at risk of neonatal hypoglycemia, and are managed according to current clinical guidelines. All babies also have continuous interstitial glucose monitoring for at least 48 h and up to 7 d after birth. Data from these monitors are not used for clinical management, but do provide valuable information about the severity, duration and frequency of low glucose concentrations. Approximately 40% of the babies develop hypoglycemia, clinically defined as a blood glucose concentration <2.6mM, and are therefore treated. However, a further 20-30% experience episodes of interstitial glucose concentrations <2.6mM that are not detected clinically and therefore are not treated. Children of consenting parents will be assessed at 2 and 4.5 years of age. The assessments will include standardised measures of growth, neurological function, vision, cognitive and language development, memory, executive function, general health and family environment. Data analysis will include multivariate modelling to assess the relationships between neonatal glucose concentrations and developmental outcomes, with appropriate adjustment for perinatal events and potential postnatal family and environmental influences. Results will provide a much-needed evidence base to inform clinical practice in the short term, while also providing the critical evidence base upon which randomized trials of appropriate interventions can be designed.