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

描述（由申请人提供）：脑功能减退是新生儿最常见的代谢紊乱，也是新生儿脑损伤的唯一已知常见可预防原因。然而，诊断和管理的最佳方法仍不清楚。一个主要的挑战是，不同婴儿发生脑损伤时的血糖浓度可能不同，并且不知道在脑损伤发生之前低血糖浓度必须发生多低，多久或多久。包括NICHD 1在内的一些机构呼吁对新生儿期测量血糖浓度的儿童进行大型随访研究，并涵盖足够宽的范围以确定血糖浓度与后期结局之间的关系。这项建议正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内低血糖浓度的严重程度、持续时间和频率有关。具体目标是确定：1。出生后第一周内记录的低血糖浓度的严重程度、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相关。2.这些关系是否在具有不同风险因素或围产期病史的婴儿中存在差异。3.什么样的葡萄糖浓度提供了最好的区分定义“低”与这些结果在不同的婴儿群体，因此可以提供一个基于证据的干预阈值。正在招募<500名足月和晚期早产儿（e35周）。所有这些都有新生儿低血糖的风险，并根据当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天内也进行连续的间质葡萄糖监测。这些监测仪的数据不用于临床管理，但确实提供了有关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，另外20-30%的患者经历了临床上未检测到的间质葡萄糖浓度<2.6mM的事件，因此未进行治疗。父母同意的儿童将在2岁和4.5岁时进行评估。评估将包括标准化的生长、神经功能、视力、认知和语言发育、记忆、执行功能、一般健康和家庭环境指标。数据分析将包括多变量建模，以评估新生儿葡萄糖浓度和发育结果之间的关系，适当调整围产期事件和潜在的产后家庭和环境影响。结果将提供急需的证据基础，在短期内告知临床实践，同时也提供了关键的证据基础上，可以设计适当的干预措施的随机试验。

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.