{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T07:11:34Z","timestamp":1787987494448,"version":"build-2784847793"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,12,16]],"date-time":"2021-12-16T00:00:00Z","timestamp":1639612800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Biosci."],"abstract":"<jats:p>\n                    <jats:bold>Introduction:<\/jats:bold>\n                    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\u00a0MS\/MS NBS biomarkers and establish accurate and robust RIs.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods:<\/jats:bold>\n                    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.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results:<\/jats:bold>\n                    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.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusion:<\/jats:bold>\n                    The present study determined the dynamic trends of 35\u00a0MS\/MS biomarkers and established age and sex-specific RIs, valuably contributing to the current literature and timely evaluation of neonatal health and disease.\n                  <\/jats:p>","DOI":"10.3389\/fmolb.2021.719866","type":"journal-article","created":{"date-parts":[[2021,12,16]],"date-time":"2021-12-16T08:26:05Z","timestamp":1639643165000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["Reference Standards for Newborn Screening of Metabolic Disorders by Tandem Mass Spectrometry: A Nationwide Study on Millions of Chinese Neonatal Populations"],"prefix":"10.3389","volume":"8","author":[{"given":"Falin","family":"He","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rulai","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinwen","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaping","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofang","family":"Pei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary Kathryn","family":"Bohn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Zou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haibo","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maosheng","family":"Gu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xigui","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Zou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongwei","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weibing","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khosrow","family":"Adeli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiguo","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,12,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1080\/10408363.2017.1379945","article-title":"The canadian Laboratory Initiative on Pediatric Reference Intervals: A Caliper white Paper","volume":"54","author":"Adeli","year":"2017","journal-title":"Crit. 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