{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T03:24:42Z","timestamp":1773458682473,"version":"3.50.1"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,12,11]],"date-time":"2024-12-11T00:00:00Z","timestamp":1733875200000},"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. Pediatr."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Down syndrome (DS) is linked to unique hematopoietic characteristics that affect complete blood count (CBC) parameters. Accurate reference ranges are essential for proper CBC interpretation in this population.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This retrospective study analyzed 2,627 CBCs from 481 DS patients, aged 31 days to 18 years, at a tertiary care center in Italy. Patients with significant comorbidities were excluded to ensure a homogeneous group.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>CBC parameters were assessed to establish age- and sex-specific reference ranges. Centile charts were developed for each parameter, and an online tool was created to allow clinicians to compare individual CBC results with the new ranges. Comparisons with the general pediatric population revealed significant differences, particularly in hemoglobin, hematocrit, and mean corpuscular volume, which were higher in DS (<jats:italic>p<\/jats:italic>\u2009&amp;lt;\u20090.001). In contrast, a significant percentage of CBCs showed white blood cell counts below the 2.5th centile of healthy controls (<jats:italic>p<\/jats:italic>\u2009&amp;lt;\u20090.001), except for the 31 days\u20131 year age group. A similar trend was observed for lymphocytes (<jats:italic>p<\/jats:italic>\u2009&amp;lt;\u20090.001) in the 1-18 years group.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>These newly established DS-specific reference ranges provide clinicians with a crucial tool for evaluating CBC results, potentially reducing unnecessary tests and emphasizing the need for tailored clinical assessment in managing this unique population.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fped.2024.1510733","type":"journal-article","created":{"date-parts":[[2024,12,11]],"date-time":"2024-12-11T04:43:11Z","timestamp":1733892191000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Reference ranges for complete blood count in children and adolescents with Down syndrome"],"prefix":"10.3389","volume":"12","author":[{"given":"Martina","family":"Lattuada","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giulia","family":"Capitoli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Casati","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra","family":"Lazzerotti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oscar","family":"Maglia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giulia Maria","family":"Ferrari","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Fossati","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Biondi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandro","family":"Cattoni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paola","family":"Corti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2024,12,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"536","DOI":"10.1002\/pd.5822","article-title":"Review of epidemiological factors (other than maternal age) that determine the prevalence of common autosomal trisomies","volume":"41","author":"Cuckle","year":"2021","journal-title":"Prenat Diagn"},{"key":"B2","doi-asserted-by":"publisher","first-page":"908482","DOI":"10.3389\/fgene.2022.908482","article-title":"Global, regional, and national burden and trends of down syndrome from 1990 to 2019","volume":"13","author":"Chen","year":"2022","journal-title":"Front Genet"},{"key":"B3","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1615\/critreveukargeneexpr.v15.i3.40","article-title":"Increased dosage of the RUNX1\/AML1 gene: a third mode of RUNX leukemia?","volume":"15","author":"Osato","year":"2005","journal-title":"Crit Rev Eukaryot Gene Expr"},{"key":"B4","doi-asserted-by":"publisher","first-page":"4507","DOI":"10.1182\/blood-2008-04-152967","article-title":"Abnormalities in the myeloid progenitor compartment in down syndrome fetal liver precede acquisition of GATA1 mutations","volume":"112","author":"Tunstall-Pedoe","year":"2008","journal-title":"Blood"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1301","DOI":"10.1007\/s00431-011-1624-1","article-title":"Hematological disorders and leukemia in children with down syndrome","volume":"171","author":"Bruwier","year":"2012","journal-title":"Eur J Pediatr"},{"key":"B6","doi-asserted-by":"publisher","first-page":"533","DOI":"10.4161\/cc.23667","article-title":"The impact of trisomy 21 on early human hematopoiesis","volume":"12","author":"Roy","year":"2013","journal-title":"Cell Cycle"},{"key":"B7","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1002\/ajmg.a.31442","article-title":"Hematological abnormalities during the first week of life among neonates with down syndrome: data from a multihospital healthcare system","author":"Henry","year":"2007","journal-title":"Am J Med Genet A"},{"key":"B8","doi-asserted-by":"publisher","first-page":"897","DOI":"10.1002\/ajmg.a.38097","article-title":"Descriptive study of the complete blood count in newborn infants with down syndrome","volume":"173","author":"Mart\u00ednez-Mac\u00edas","year":"2017","journal-title":"Am J Med Genet A"},{"key":"B9","doi-asserted-by":"publisher","first-page":"664","DOI":"10.24953\/turkjped.2019.05.004","article-title":"Hematological disturbances in down syndrome: single centre experience of thirteen years and review of the literature","volume":"61","author":"Karakurt","year":"2019","journal-title":"Turk J Pediatr"},{"key":"B10","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1111\/j.1751-553X.2011.01299.x","article-title":"Distinctive hematological abnormalities in East Asian neonates and children with down syndrome","volume":"33","author":"Kim","year":"2011","journal-title":"Int J Lab Hematol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1111\/j.1399-0004.1996.tb04318.x","article-title":"Peripheral blood cell counts in infants with down\u2019s syndrome","volume":"49","author":"Kivivuori","year":"1996","journal-title":"Clin Genet"},{"key":"B12","doi-asserted-by":"publisher","first-page":"271","DOI":"10.3109\/08880019609030827","article-title":"Hematological studies in children with down syndrome","volume":"13","author":"David","year":"1996","journal-title":"Pediatr Hematol Oncol"},{"key":"B13","doi-asserted-by":"publisher","first-page":"510","DOI":"10.1002\/ajmg.1320460509","article-title":"Hematologic abnormalities in children with down syndrome","volume":"46","author":"Roizen","year":"1993","journal-title":"Am J Med Genet"},{"key":"B14","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1007\/s11845-008-0223-2","article-title":"Hematological abnormalities in adult patients with down\u2019s syndrome","volume":"178","author":"McLean","year":"2009","journal-title":"Ir J Med Sci"},{"key":"B15","doi-asserted-by":"publisher","first-page":"146663","DOI":"10.1016\/j.gene.2022.146663","article-title":"Leukopenia, macrocytosis, and thrombocytopenia occur in young adults with down syndrome","volume":"835","author":"Hamaguchi","year":"2022","journal-title":"Gene"},{"key":"B16","doi-asserted-by":"publisher","first-page":"930","DOI":"10.1046\/j.1365-2141.2003.04229.x","article-title":"Transient leukaemia\u2014a benign form of leukaemia in newborn infants with trisomy 21","volume":"120","author":"Zipursky","year":"2003","journal-title":"Br J Kaematol"},{"key":"B17","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1080\/17474086.2022.2044780","article-title":"Hematological disorders in children with down syndrome","volume":"15","author":"Triarico","year":"2022","journal-title":"Expert Rev Hematol"},{"key":"B18","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1186\/s12887-022-03450-8","article-title":"Blood cytology in children with down syndrome","volume":"22","author":"Garc\u00eda de la Puente","year":"2022","journal-title":"BMC Pediatr"},{"key":"B19","doi-asserted-by":"publisher","first-page":"e30002","DOI":"10.1002\/pbc.30002","article-title":"Blood counts in children with down syndrome","volume":"69","author":"Harvey","year":"2022","journal-title":"Pediatr Blood Cancer"},{"key":"B20","doi-asserted-by":"publisher","first-page":"750","DOI":"10.1111\/ijlh.13306","article-title":"Complex biological patterns of hematology parameters in childhood necessitating age- and sex-specific reference intervals for evidence-based clinical interpretation","volume":"42","author":"Bohn","year":"2020","journal-title":"Int J Lab Hematol"},{"key":"B21","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1515\/cclm-2021-0853","article-title":"Indirectly determined hematology reference intervals for pediatric patients in Berlin and Brandenburg","volume":"60","author":"Mrosewski","year":"2021","journal-title":"Clin Chem Lab Med"},{"key":"B22","doi-asserted-by":"publisher","first-page":"1116","DOI":"10.1515\/cclm-2022-1265","article-title":"Indirectly determined reference intervals for automated white blood cell differentials of pediatric patients in Berlin and Brandenburg","volume":"61","author":"Mrosewski","year":"2023","journal-title":"Clin Chem Lab Med"},{"key":"B23","doi-asserted-by":"publisher","first-page":"1869","DOI":"10.1002\/stem.507","article-title":"A Runx1 intronic enhancer marks hemogenic endothelial cells and hematopoietic stem cells","volume":"28","author":"Ng","year":"2010","journal-title":"Stem Cells"},{"key":"B24","doi-asserted-by":"publisher","first-page":"3337","DOI":"10.1182\/blood-2008-08-174813","article-title":"ETS2 and ERG promote megakaryopoiesis and synergize with alterations in GATA-1 to immortalize hematopoietic progenitor cells","volume":"113","author":"Stankiewicz","year":"2009","journal-title":"Blood J Am Soc Hematol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1038\/nature12530","article-title":"Usp16 contributes to somatic stem-cell defects in down\u2019s syndrome","volume":"501","author":"Adorno","year":"2013","journal-title":"Nature"},{"key":"B26","doi-asserted-by":"publisher","first-page":"5187","DOI":"10.2147\/JIR.S280953","article-title":"Interferon-Driven immune dysregulation in down syndrome: a review of the evidence","volume":"14","author":"Chung","year":"2021","journal-title":"J Inflamm Res"},{"key":"B27","doi-asserted-by":"publisher","first-page":"2779","DOI":"10.1210\/clinem\/dgad333","article-title":"Thyroid function tests in children and adolescents with trisomy 21: definition of syndrome-specific reference ranges","volume":"108","author":"Cattoni","year":"2023","journal-title":"J Clin Endocrinol Metab"},{"key":"B28","doi-asserted-by":"publisher","first-page":"702","DOI":"10.1515\/CCLM.2004.120","article-title":"Selecting clinically relevant populations for reference intervals","volume":"42","author":"Ritchie","year":"2004","journal-title":"Clin Chem Lab Med"},{"key":"B29","doi-asserted-by":"publisher","first-page":"1595","DOI":"10.1515\/cclm-2018-1236","article-title":"Next-generation reference intervals for pediatric hematology","volume":"57","author":"Zierk","year":"2019","journal-title":"Clin Chem Lab Med"},{"key":"B30","doi-asserted-by":"publisher","first-page":"101653","DOI":"10.1016\/j.beem.2022.101653","article-title":"Haematological actions of androgens","volume":"36","author":"Warren","year":"2022","journal-title":"Best Pract Res Clin Endocrinol Metab"},{"key":"B31","doi-asserted-by":"publisher","first-page":"100586","DOI":"10.1016\/j.blre.2019.06.003","article-title":"Benign ethnic neutropenia","volume":"37","author":"Atallah-Yunes","year":"2019","journal-title":"Blood Rev"}],"container-title":["Frontiers in Pediatrics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2024.1510733\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,11]],"date-time":"2024-12-11T04:43:14Z","timestamp":1733892194000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2024.1510733\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,11]]},"references-count":31,"alternative-id":["10.3389\/fped.2024.1510733"],"URL":"https:\/\/doi.org\/10.3389\/fped.2024.1510733","relation":{},"ISSN":["2296-2360"],"issn-type":[{"value":"2296-2360","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,11]]},"article-number":"1510733"}}