Reference Standards for Newborn Screening of Metabolic Disorders by Tandem Mass Spectrometry: A Nationwide Study on Millions of Chinese Neonatal Populations

Frontiers in Molecular Biosciences

Tao Jiang¹  Xigui Chen²  Hui Zou³  Hongwei Wei⁴  Weibing Tian⁵  Yaping Tian⁶  Yan Wang⁶  Xinwen Huang⁷  Rulai Yang⁷  Xiaofang Pei⁸  Tian Tang⁸  Khosrow Adeli⁹  Mary Kathryn Bohn⁹  Zhiguo Wang^1,10  Falin He^1,10  Haibo Li^1,11  Ting Wang^1,12  Lin Zou^1,13  Maosheng Gu^1,14 

[1] 0Nanjing Maternity and Child Health Care Hospital, Nanjing, China;1Jining Maternal and Child Health Family Planning Service Center, Jining, China;2Jinan Maternity and Child Care Hospital Affiliated to Shandong First Medical University, Jinan, China;3Linyi Maternity and Child Health Care Hospital, Linyi, China;4W. F. Maternal and Child Health Hospital, Weifang, China;Chinese PLA General Hospital and Medical School of Chinese PLA, Beijing, China;Department of Genetics and Metabolism, Children’s Hospital of Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China;Department of Laboratory Sciences, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China;Department of Pediatric Laboratory Medicine, CALIPER Program, The Hospital for Sick Children, Toronto, ON, Canada;National Center for Clinical Laboratories, Beijing Engineering Research Center of Laboratory Medicine, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China;Ningbo Women and Children’s Hospital, Ningbo, China;Suzhou Municipal Hospital, Suzhou, China;The Children’s Hospital of Chongqing Medical University, Chongqing, China;The Xuzhou Maternity and Child Health Care Hospital, Xuzhou, China;

关键词: newborn screening;    inborn errors of metabolism;    mass spectrometry;    reference intervals;    biomarkers;   

DOI  :  10.3389/fmolb.2021.719866

来源: DOAJ

【 摘 要 】

Introduction: The major clinical problem presently confronting the Chinese newborn screening (NBS) programs by tandem mass spectrometry (MS/MS) is the lack of comprehensive reference intervals (RIs) for disease biomarkers. To close this gap, the Chinese National Center for Clinical Laboratories (NCCL) launched a nationwide study to investigate the dynamic pattern of 35 MS/MS NBS biomarkers and establish accurate and robust RIs.Methods: Blood spot samples from 4,714,089 Chinese neonates were tested in participating centers/laboratories and used for study analysis. MS/MS NBS biomarker trends were visually assessed by their concentrations over age. Specific partitions were determined arbitrarily by each day and sex or by the statistical method of Harris and Boyd. RIs, corresponding to the 2.5th and 97.5th percentiles, as well as the 1th, 25th, 75th and 99th percentiles were calculated for each reference partition using a non-parametric rank approach.Results: Most MS/MS NBS biomarkers fluctuated during the first week of life, followed by a relatively stable concentration. Age and sex-specific RIs were established and presented an improved specificity over the RIs used in participating centers/laboratories. Females demonstrated higher 2.5th and 97.5th percentiles in all amino acids except arginine and ornithine than males, whereas males showed higher 2.5th and 97.5th percentiles in most acylcarnitines.Conclusion: The present study determined the dynamic trends of 35 MS/MS biomarkers and established age and sex-specific RIs, valuably contributing to the current literature and timely evaluation of neonatal health and disease.

【 授权许可】

Unknown