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

患有低血糖的儿童及其后期发育（CHYLD 研究）

• 批准号: 8898161
• 负责人: Jane Harding
• 金额: $ 23.84万
• 依托单位: UNIVERSITY OF AUCKLAND
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-15 至 2017-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8898161
• 关键词: Age-Years; Birth; Blood Glucose; Brain Injuries; Child; Childhood; Clinical; Clinical Management; Consent; Data; Data Analyses; Development; Diagnosis; Environment; Event; Family; Family health status; Frequencies; Glucose; Growth; Guidelines; Hour; Hypoglycemia; Intellectual functioning disability; Intervention; Language Development; Measures; Memory; Metabolic Diseases; Modeling; Monitor; Neonatal; Neonatal Hypoglycemia; Nervous System Physiology; Newborn Infant; Outcome; Parents; Performance; Perinatal; Premature Infant; Recording of previous events; Recruitment Activity; Research; Risk; Risk Factors; Schools; Severities; Testing; Time; clinical practice; cognitive development; cohort; cost; design; early childhood; evidence base; executive function; experience; follow-up; glucose monitor; interstitial; neonatal care; postnatal; prevent; randomized trial; standard care; standardize measure; sugar; vision development

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.

描述（由申请人提供）：低血糖是新生儿最常见的代谢紊乱，也是新生儿脑损伤的唯一已知的常见可预防原因。然而，诊断和管理的最佳方法仍不清楚。一项主要挑战是，不同婴儿造成脑损伤的血糖浓度可能有所不同，并且尚不清楚在发生脑损伤之前必须出现低血糖浓度、低血糖浓度多低、频率有多低或持续多长时间。包括 NICHD1 在内的人们呼吁对儿童进行大规模后续研究，在新生儿时期测量血糖浓度，并涵盖足够宽的范围以确定血糖浓度与后期结果之间的关系。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血糖浓度的严重程度、持续时间和频率有关。具体目的是确定： 1. 出生后第一周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果相关。 2. 对于具有不同危险因素或围产期史的婴儿，这些关系是否有所不同。 3. 相对于不同婴儿组的这些结果，什么葡萄糖浓度提供了“低”的最佳区分定义，因此可以提供基于证据的干预阈值。正在招募<500 名足月儿和晚期早产儿（35 周以下）的队列。所有人都面临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 天内还要进行连续间质葡萄糖监测。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（临床上定义为血糖浓度<2.6mM），因此需要接受治疗。然而，另外 20-30% 的患者出现间质葡萄糖浓度<2.6mM，但临床上未检测到，因此未进行治疗。父母同意的儿童将在 2 岁和 4.5 岁时接受评估。评估将包括生长、神经功能、视力、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，以评估新生儿葡萄糖浓度与发育结果之间的关系，并对围产期事件以及潜在的产后家庭和环境影响进行适当调整。结果将为短期内的临床实践提供急需的证据基础，同时也提供设计适当干预措施的随机试验的关键证据基础。

项目成果

Global motion perception is associated with motor function in 2-year-old children.

• DOI: 10.1016/j.neulet.2017.08.062
• 发表时间: 2017-09-29
• 期刊: Neuroscience letters
• 影响因子: 2.5
• 作者: Thompson B;McKinlay CJD;Chakraborty A;Anstice NS;Jacobs RJ;Paudel N;Yu TY;Ansell JM;Wouldes TA;Harding JE;CHYLD Study Team
• 通讯作者: CHYLD Study Team

Cost Analysis of Treating Neonatal Hypoglycemia with Dextrose Gel.

• DOI: 10.1016/j.jpeds.2018.02.036
• 发表时间: 2018-07
• 期刊: The Journal of pediatrics
• 作者: Glasgow MJ;Harding JE;Edlin R;Children with Hypoglycemia and Their Later Development (CHYLD) Study Team
• 通讯作者: Children with Hypoglycemia and Their Later Development (CHYLD) Study Team

Pre-school screening for developmental and emotional health: Comparison with neurodevelopmental assessment.

• DOI: 10.1111/jpc.13169
• 发表时间: 2016-06
• 期刊: Journal of paediatrics and child health
• 影响因子: 1.7
• 作者: Burakevych N;McKinlay CJ;Alsweiler JM;Wouldes TA;Harding JE
• 通讯作者: Harding JE

Neonatal Glycemia and Neurodevelopmental Outcomes at 2 Years.

• DOI: 10.1056/nejmoa1504909
• 发表时间: 2015-10-15
• 期刊: The New England journal of medicine
• 作者: McKinlay CJ;Alsweiler JM;Ansell JM;Anstice NS;Chase JG;Gamble GD;Harris DL;Jacobs RJ;Jiang Y;Paudel N;Signal M;Thompson B;Wouldes TA;Yu TY;Harding JE;CHYLD Study Group
• 通讯作者: CHYLD Study Group

Outcome at 2 Years after Dextrose Gel Treatment for Neonatal Hypoglycemia: Follow-Up of a Randomized Trial.

• DOI: 10.1016/j.jpeds.2015.10.066
• 发表时间: 2016-03
• 期刊: The Journal of pediatrics
• 作者: Harris DL;Alsweiler JM;Ansell JM;Gamble GD;Thompson B;Wouldes TA;Yu TY;Harding JE;Children with Hypoglycaemia and their Later Development (CHYLD) Study Team
• 通讯作者: Children with Hypoglycaemia and their Later Development (CHYLD) Study Team