Dynamic biological changes in metabolic disease biomarkers in childhood and adolescence: A CALIPER study of healthy community children

Dynamic biological changes in metabolic disease biomarkers in childhood and adolescence: A CALIPER study of healthy community children
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DOI:
10.1016/j.clinbiochem.2015.05.005
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发表时间:
2015-09-01
影响因子:
2.8
通讯作者:
Adeli, Khosrow
Adeli, Khosrow
中科院分区:
医学3区
文献类型:
--
作者:
Teodoro-Morrison, Tracy;Kyriakopoulou, Lianna;Adeli, Khosrow

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背景资料:了解代谢性疾病生物标志物的年龄和性别特异性生物学变化对于其在先天性代谢缺陷(IEM)儿童管理中的适当利用至关重要。CALIPER项目旨在建立健康社区儿童常见代谢生物标志物的儿科参考值,并确定关键协变量(包括年龄和性别)对儿科年龄的影响。方法:首先招募500名健康儿童和青少年(从出生到19岁),根据CLSI C28-A3指南建立儿科参考区间。血清样品用于测量37个氨基酸的超高效液相色谱法,32酰基肉毒碱,以及游离和总肉毒碱的串联质谱法,β-羟基丁酸和游离脂肪酸使用Vitros 5.1化学分析仪。使用非参数统计和分区的基础上年龄和性别distribution.Results:大约80%的所有分析物需要2至4个年龄相关的分区,超过50%的氨基酸和超过70%的酰基肉毒碱表现出显着的生理变化,在新生儿期。此外,21%的所有分析物需要分区在青春期和青春期,其中一半产生的性别特异性distributions.Conclusions:一个全面的参考区间数据库代谢疾病的生物标志物在这项研究中建立将提高检测IEMS提供适当的年龄和性别相关的信息在儿科人群。它还将帮助新生儿筛查计划,并指导已知代谢疾病患者的管理,特别是显示性别特异性浓度的青春期和青春期男孩和女孩。(C)2015年加拿大临床化学家协会。爱思唯尔公司出版All rights reserved.
Background: Understanding age- and sex-specific biological changes in metabolic disease biomarkers is essential for their appropriate utilization in management of children with inborn errors of metabolism (IEM). The CALIPER program aimed to establish pediatric reference values in healthy community children for common metabolic biomarkers and determine the effects of key covariates including age and sex across the pediatric age.Methods: A cohort of 500 healthy children and adolescents from birth to 19 years were initially recruited to establish pediatric reference intervals according to the CLSI C28-A3 guidelines. Serum samples were used to measure 37 amino acids by ultra-performance liquid chromatography, 32 acylcarnitines, as well as free and total carnitine by tandem mass spectrometry, and beta-hydroxybutyrate and free fatty acids using the Vitros 5.1 chemistry analyzer. Pediatric reference intervals were calculated using non-parametric statistics and partitioned based on age- and sex-distributions.Results: Approximately 80% of all analytes required 2 to 4 age-dependent partitions, with over 50% of amino acids and over 70% of acylcarnitines exhibiting significant physiological changes during the neonatal period. Also, 21% of all analytes required partitioning during puberty and adolescence, half of which produced sex-specific distributions.Conclusions: A comprehensive reference interval database for metabolic disease biomarkers established in this study will improve detection of IEMs by providing appropriate age- and sex-related information in the pediatric population. It will also aid newborn screening programs and guide the management of patients with known metabolic diseases, especially pubertal and adolescent boys and girls that display sex-specific concentrations. (C) 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.