{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T10:01:45Z","timestamp":1789984905738,"version":"4.0.1"},"reference-count":58,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,5,24]],"date-time":"2026-05-24T00:00:00Z","timestamp":1779580800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,5,24]],"date-time":"2026-05-24T00:00:00Z","timestamp":1779580800000},"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":["Health Science Reports"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Individuals with Down syndrome (DS) require specialized medical follow\u2010up and services more frequently than the general population, resulting in substantial healthcare costs for families and health systems. This systematic review aimed to synthesize evidence on the magnitude and determinants of direct healthcare and indirect costs associated with DS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We searched Web of Science, PubMed, and Scopus for observational and experimental studies published in English between January 1, 2000, and December 31, 2022 (updated June 15, 2024), that reported healthcare costs or cost determinants for individuals with DS. Reference lists were also screened. We excluded non\u2010English papers, qualitative studies, reviews, protocols, editorials, and gray literature.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The search identified 625 unique citations, of which 14 matched the inclusion criteria. Half were conducted in the USA. Inpatient services constituted the largest share of direct healthcare costs in 58% of studies. Indirect costs, mainly productivity losses among families, were reported in 25% of studies. Healthcare costs were highest during infancy (driven primarily by congenital heart defects and early hospitalizations), decreased throughout childhood and adolescence, and increased again in adulthood, particularly after age 40, due to age\u2010related comorbidities such as dementia and multimorbidity. Associated morbidities, greater functional limitations, and lower socioeconomic status were consistently associated with higher costs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Age, comorbidities, functional ability, and socioeconomic factors are key drivers of healthcare costs in DS. Long\u2010term, comprehensive policies integrating medical, social, and educational support are needed. Priority should be given to early cardiac surgery coverage, multidisciplinary adult transition clinics, subsidized respite care, and financial assistance schemes to reduce both inpatient utilization and family productivity losses.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hsr2.72297","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T04:51:00Z","timestamp":1779684660000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Determinants of Healthcare Costs in Individuals With Down Syndrome: A Systematic Review"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1298-189X","authenticated-orcid":false,"given":"Shiva Tolouei","family":"Rakhshan","sequence":"first","affiliation":[{"name":"Department of Health Management, Policy and Economics, School of Public Health Tehran University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7084-1495","authenticated-orcid":false,"given":"Sarah","family":"Byford","sequence":"additional","affiliation":[{"name":"King's Health Economics, King's College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8764-587X","authenticated-orcid":false,"given":"Mahya","family":"Razimoghadam","sequence":"additional","affiliation":[{"name":"Department of Health Management, Policy and Economics, School of Public Health Tehran University of Medical Sciences Tehran Iran"},{"name":"National Center for Health Insurance Research Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fardin","family":"Moradi","sequence":"additional","affiliation":[{"name":"Medical Education Department Center (EDC) Kurdistan University of Medical Sciences Sanandaj Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8365-7363","authenticated-orcid":false,"given":"Shahin","family":"Soltani","sequence":"additional","affiliation":[{"name":"Research Center for Environmental Determinants of Health (RCEDH), Health Institute Kermanshah University of Medical Sciences Kermanshah Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,24]]},"reference":[{"issue":"3","key":"e_1_2_15_2_1","first-page":"125","article-title":"Down Syndrome: Current Status, Challenges and Future Perspectives","volume":"5","author":"Kazemi M.","year":"2016","journal-title":"International Journal of Molecular and Cellular Medicine"},{"key":"e_1_2_15_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2012.94"},{"key":"e_1_2_15_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.38512"},{"key":"e_1_2_15_5_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-3016.2000.00252.x"},{"key":"e_1_2_15_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-8749.2004.tb00483.x"},{"key":"e_1_2_15_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)12987-X"},{"key":"e_1_2_15_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2008.02.046"},{"key":"e_1_2_15_9_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-170624"},{"key":"e_1_2_15_10_1","unstructured":"N.Waitzman R. M.Scheffler andP. S.RomanoThe Cost of Birth Defects: Estimates of the Value of Protection.1996."},{"key":"e_1_2_15_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.35706"},{"key":"e_1_2_15_12_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2018.2210"},{"key":"e_1_2_15_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2011.06.007"},{"key":"e_1_2_15_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20409"},{"issue":"37","key":"e_1_2_15_15_1","first-page":"694","article-title":"Economic Costs of Birth Defects and Cerebral Palsy\u2010\u2010United States, 1992","volume":"44","author":"Control CfD, Prevention","year":"1995","journal-title":"MMWR. Morbidity and Mortality Weekly Report"},{"key":"e_1_2_15_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(02)08092-3"},{"key":"e_1_2_15_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ridd.2013.06.022"},{"key":"e_1_2_15_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.38050"},{"key":"e_1_2_15_19_1","doi-asserted-by":"publisher","DOI":"10.3346\/jkms.2019.34.e207"},{"key":"e_1_2_15_20_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0208076"},{"key":"e_1_2_15_21_1","doi-asserted-by":"publisher","DOI":"10.3109\/13668250.2015.1087479"},{"key":"e_1_2_15_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rehab.2020.07.011"},{"key":"e_1_2_15_23_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-171067"},{"key":"e_1_2_15_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.23295"},{"key":"e_1_2_15_25_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2788.2002.00392.x"},{"key":"e_1_2_15_26_1","unstructured":"C.Stoll Y.Alembik B.Dott andM.Roth editors. Study of Down Syndrome in 238 942 Consecutive Births. Annales de Genetique;1998."},{"key":"e_1_2_15_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19980605)77:5<431::AID-AJMG15>3.0.CO;2-J"},{"key":"e_1_2_15_28_1","unstructured":"B.DobsonandS.MiddletonPaying to Care: The Cost of Childhood Disability: York Publishing Services for the Joseph Rowntree Foundation;1998."},{"key":"e_1_2_15_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ridd.2011.02.024"},{"key":"e_1_2_15_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2011.04.019"},{"key":"e_1_2_15_31_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2008-1440"},{"key":"e_1_2_15_32_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2018.3616"},{"key":"e_1_2_15_33_1","doi-asserted-by":"publisher","DOI":"10.1097\/MRR.0000000000000147"},{"key":"e_1_2_15_34_1","doi-asserted-by":"publisher","DOI":"10.1186\/s11689-019-9306-9"},{"key":"e_1_2_15_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2788.2007.01013.x"},{"key":"e_1_2_15_36_1","doi-asserted-by":"publisher","DOI":"10.1044\/jshr.3405.1106"},{"key":"e_1_2_15_37_1","unstructured":"B. D.ZahedandI.AsadpourThe Challenges Related to the Education Physical Job and Future of Children With Down Syndrome."},{"key":"e_1_2_15_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/jar.12446"},{"issue":"2","key":"e_1_2_15_39_1","first-page":"393","article-title":"Health Supervision for Children With Down Syndrome","volume":"128","author":"Bull MJ, Genetics Co","year":"2011","journal-title":"American Academy of Pediatrics Elk Grove Village, IL, USA"},{"key":"e_1_2_15_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2008.01110.x"},{"key":"e_1_2_15_41_1","doi-asserted-by":"publisher","DOI":"10.1159\/000321767"},{"key":"e_1_2_15_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/pd.4516"},{"key":"e_1_2_15_43_1","doi-asserted-by":"publisher","DOI":"10.1111\/jir.12390"},{"key":"e_1_2_15_44_1","doi-asserted-by":"publisher","DOI":"10.3310\/hta2010"},{"key":"e_1_2_15_45_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.305.6850.391"},{"key":"e_1_2_15_46_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.AOG.0000214953.90248.db"},{"key":"e_1_2_15_47_1","first-page":"227","article-title":"Center for Parent Information and Resources","volume":"1","author":"Colomeischi A. A.","year":"2018","journal-title":"Book Chapters\u2010Educational Sciences, Sports and Psychology"},{"key":"e_1_2_15_48_1","unstructured":"B. A.Khan W. A.Zargar andS. A.NajarExploring Support System for Parents of Children With Disability: Role of Religion."},{"issue":"4","key":"e_1_2_15_49_1","first-page":"462","article-title":"The Effect of the Presence of an Elderly Member on Health Care Costs of Iranian Households","volume":"14","author":"Yahyavi Dizaj J.","year":"2020","journal-title":"Salmand: Iranian Journal of Ageing"},{"key":"e_1_2_15_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejim.2015.05.003"},{"key":"e_1_2_15_51_1","doi-asserted-by":"publisher","DOI":"10.52547\/JPS.21.115.1285"},{"key":"e_1_2_15_52_1","doi-asserted-by":"publisher","DOI":"10.1353\/foc.2012.0008"},{"key":"e_1_2_15_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0074-7750(10)39009-4"},{"key":"e_1_2_15_54_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamapediatrics.2014.210"},{"key":"e_1_2_15_55_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2013-0763"},{"key":"e_1_2_15_56_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.296.16.1981"},{"key":"e_1_2_15_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2008.02.046"},{"key":"e_1_2_15_58_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2011-1605"},{"key":"e_1_2_15_59_1","doi-asserted-by":"publisher","DOI":"10.1186\/s11689-019-9306-9"}],"updated-by":[{"DOI":"10.1002\/hsr2.73116","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000}}],"container-title":["Health Science Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/hsr2.72297","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/hsr2.72297","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/hsr2.72297","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T09:12:59Z","timestamp":1789981979000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/hsr2.72297"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,24]]},"references-count":58,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["10.1002\/hsr2.72297"],"URL":"https:\/\/doi.org\/10.1002\/hsr2.72297","archive":["Portico"],"relation":{},"ISSN":["2398-8835","2398-8835"],"issn-type":[{"value":"2398-8835","type":"print"},{"value":"2398-8835","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,24]]},"assertion":[{"value":"2025-09-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-28","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-24","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e72297"}}