{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T06:50:52Z","timestamp":1774421452852,"version":"3.50.1"},"reference-count":37,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T00:00:00Z","timestamp":1774224000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Beijing Natural Science Foundation\u2013Daxing Innovation Joint Fund","award":["L256080"],"award-info":[{"award-number":["L256080"]}]},{"name":"Peking Union Medical College Hospital Youth Category-D Program","award":["UHB12728"],"award-info":[{"award-number":["UHB12728"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["72274218"],"award-info":[{"award-number":["72274218"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background: Conventional reference intervals (RIs) are typically expressed as fixed limits and may not adequately reflect continuous biological variation across age and sex. Next-generation reference intervals (NGRIs) allow dynamic modeling of laboratory parameters across the lifespan. This study aimed to establish age- and sex-specific NGRIs for routine hematological parameters using large-scale health examination data and to evaluate their temporal stability. Methods: Health examination records were linked with laboratory data, and a relatively healthy reference population was defined based on age (18\u201380 years), normal body mass index, normal blood pressure, and absence of documented disease history. NGRIs were constructed using generalized additive models for location, scale, and shape (GAMLSS) with the Box\u2013Cox Cole and Green distribution. Age-dependent percentile curves (2.5th\u201397.5th) were generated using bootstrap resampling (100 iterations). Temporal external validation was conducted in five independent annual cohorts (2019\u20132023). Results: Age- and sex-dependent distributional patterns were observed across multiple hematological parameters, particularly RBC, HGB, and HCT. Continuous percentile curves demonstrated gradual age-related trends, with more pronounced changes in females after midlife. In temporal validation cohorts, the proportion of individuals classified outside the reference intervals remained consistently below 10% across years and sexes, indicating stable performance. Conclusions: Using large-scale real-world health examination data and a flexible distributional modeling framework, we established stable age-continuous next-generation reference intervals for routine hematological parameters. The proposed approach provides a reproducible strategy for modernizing laboratory reference interval construction and supports broader implementation in population-based laboratory medicine.<\/jats:p>","DOI":"10.3390\/diagnostics16060944","type":"journal-article","created":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T13:53:34Z","timestamp":1774274014000},"page":"944","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Establishment and Temporal Validation of Next-Generation Reference Intervals for Routine Hematological Parameters Using Large-Scale Data"],"prefix":"10.3390","volume":"16","author":[{"given":"Chaochao","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing 100730, China"},{"name":"Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, Beijing 100191, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lihua","family":"Guan","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing 100730, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qian","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing 100730, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rongrong","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing 100730, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing 100730, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ling","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing 100730, China"},{"name":"State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing 100730, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1515\/cclm-2018-0073","article-title":"Indirect methods for reference interval determination\u2014Review and recommendations","volume":"57","author":"Jones","year":"2018","journal-title":"Clin. 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