{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T03:57:05Z","timestamp":1790913425146,"version":"4.1.0"},"reference-count":35,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T00:00:00Z","timestamp":1741737600000},"content-version":"vor","delay-in-days":70,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatrics International"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The association between Down syndrome (DS) and hyperuricemia has been described for a long time. The cut\u2010off points for hyperuricemia should be determined as the upper limits of the uric acid (UA) level according to age\u2010 and gender\u2010specific reference UA values prepared for children with DS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study included 238 children (140 males and 98 females) with DS, below 21\u2009years of age, who visited our medical center from May 1991 to June 31, 2018. Laboratory data were used to calculate the reference UA levels according to age and gender. We also inquired about the relationship between hyperuricemia and the presence of other diseases and other laboratory findings in children with DS. Fourteen patients had already been definitively diagnosed and treated. The UA data from these cases were excluded from the analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The UA levels were significantly higher in all age groups among individuals with DS in comparison with the general population. Newly established reference values revealed 55 patients with hyperuricemia. The prevalence of hyperuricemia in males and females was 25.0% (35\/140) and 20.4% (20\/98), respectively. The number of hyperuricemia cases increased rapidly after 10\u2009years of age. The UA levels were closely correlated with hemoglobin (Hb) values, creatinine, and total bilirubin, which are closely associated with dehydration in children with DS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These reference levels could help to evaluate hyperuricemia candidates who should be carefully monitored and treated with uric\u2010acid\u2010lowering drugs in the future.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/ped.15863","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T06:35:04Z","timestamp":1741761304000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Age and gender\u2010specific reference intervals for uric acid level and hyperuricemia in children with Down syndrome"],"prefix":"10.1111","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5519-8320","authenticated-orcid":false,"given":"Toshiyuki","family":"Kitoh","sequence":"first","affiliation":[{"name":"Laboratory of Pediatrics Aichi Gakuin University, School of Pharmacy  Nagoya Japan"},{"name":"Shiga Medical Center for Children  Moriyama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuro","family":"Yamana","sequence":"additional","affiliation":[{"name":"Laboratory of Pediatrics Aichi Gakuin University, School of Pharmacy  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirofumi","family":"Imura","sequence":"additional","affiliation":[{"name":"Laboratory of Pediatrics Aichi Gakuin University, School of Pharmacy  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumihito","family":"Nozaki","sequence":"additional","affiliation":[{"name":"Shiga Medical Center for Children  Moriyama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7938-1576","authenticated-orcid":false,"given":"Takashi","family":"Kusunoki","sequence":"additional","affiliation":[{"name":"Shiga Medical Center for Children  Moriyama Japan"},{"name":"Laboratory of Child Health and Nutrition, Department of Food Science and Human Nutrition, Faculty of Agriculture Ryukoku University  Otsu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tohru","family":"Futami","sequence":"additional","affiliation":[{"name":"Shiga Medical Center for Children  Moriyama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuya","family":"Fujii","sequence":"additional","affiliation":[{"name":"Shiga Medical Center for Children  Moriyama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,3,12]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1997.4866"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)12987-X"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.137.3533.868"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00467-005-1825-9"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/apa.12664"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.122.17956"},{"issue":"3","key":"e_1_2_8_8_1","article-title":"Elevated serum uric acid and cardiovascular disease: a review and potential therapeutic interventions","volume":"14","author":"Freilich M","year":"2022","journal-title":"Cureus"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arcped.2016.08.029"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.26442\/00403660.2022.12.201999"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(96)70322-0"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.6032\/gnam.33.37"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12882-015-0047-z"},{"issue":"1","key":"e_1_2_8_14_1","first-page":"34","article-title":"Clinical course of juvenile\u2010onset hyperuricemia complicated by Down's syndrome: close correlation with thyroid dysfunction and high obesity","volume":"23","author":"Kitoh T","year":"2020","journal-title":"Int J Rheum Dis"},{"key":"e_1_2_8_15_1","unstructured":"MizunoS.Health Management of Adults with down syndrome. Aichi Colony Library Aichi Colony Central Hospital for the Mentally and Physically Handicapped Aichi Japan2023."},{"issue":"10","key":"e_1_2_8_16_1","first-page":"2123","article-title":"Down syndrome and hyperuricemia","volume":"64","author":"Taniguchi A","year":"2011","journal-title":"Jap J Pediatr"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1967.23.4.579"},{"issue":"1","key":"e_1_2_8_18_1","first-page":"103","article-title":"Renal impairment in urate excretion in patients with Down's syndrome","volume":"6","author":"Nishida Y","year":"1979","journal-title":"J Rheumatol"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-28-4-472"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/ped.13525"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00431-021-04078-z"},{"key":"e_1_2_8_22_1","unstructured":"Tips to Drink More Water_ I Need It You Need It We all need it!Boston PATIENT EDUCATION Massachusetts General Hospital; Down Syndrome Program [Cited 2022 Nov 2]. Available from:https:\/\/www.massgeneral.org\/children\/down\u2010syndrome\/tips\u2010to\u2010drink\u2010more\u2010water"},{"issue":"7","key":"e_1_2_8_23_1","first-page":"1117","article-title":"Reference intervals of clinical tests in children determined by a latent reference value extraction method","volume":"112","author":"Tanaka T","year":"2008","journal-title":"J Jap Pediatr Soc"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.657627"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.6065\/apem.1938156.078"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2019.306431"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1080\/15257770.2011.597370"},{"key":"e_1_2_8_28_1","first-page":"60","article-title":"Hyperuricemia in pediatrics revised 3rd edition. 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