{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T15:10:18Z","timestamp":1789657818944,"version":"4.0.1"},"reference-count":37,"publisher":"American Medical Association (AMA)","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"\n Importance<\/jats:title>\n Whole genome sequencing (WGS) is increasingly used to diagnose children with severe illness, yet the long-term association of a genetic diagnosis with health care utilization and resource allocation remains poorly understood.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n \n To assess the association of a genetic diagnosis through WGS with long-term health care utilization metrics in children and young people (hereafter\n children<\/jats:italic>\n ) with severe illness.\n <\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This multicenter retrospective cohort study of children aged 0 to 18 years who were severely ill who underwent WGS used data from The Next Generation of Children Project (from December 2016 to August 2020) with medical record linkage and analysis of primary care medical records conducted between January 2022 and June 2024. The primary care and hospital medical records were linked using the UK National Institute for Health and Care Research Rare Disease BioResource, Cambridge.<\/jats:p>\n <\/jats:sec>\n \n Exposures<\/jats:title>\n Receipt of a genetic diagnosis compared with those who remained undiagnosed following WGS.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n The main outcome was a comparison of 36 health care utilization parameters, including hospitalizations, primary care prescriptions, and diagnostic tests.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Among the 270 children analyzed (mean [SD] age 8.65 [6.58-9.46] years; 149 males [55.2%]), those receiving a genetic diagnosis (87 [32.2%]) exhibited significantly higher overall health care utilization compared with undiagnosed peers (183 [67.8%]). This included an increase in median (IQR) hospital admissions (37 [18-66] vs 22 [10-35]) and more primary and secondary care outpatient visits each year (14 [7-26] vs 8 [4-13]), particularly for neurodevelopmental (annual treatment costs: \u00a31280 [\u00a3507-\u00a32529] vs \u00a3130 [\u00a321-\u00a3354]) and seizure-related (annual treatment costs: \u00a31277 [\u00a3320-\u00a32271] vs \u00a360 [\u00a315-\u00a3143]) conditions. Children with genetic diagnoses received a median (IQR) higher volume of neurological (48 [22-88] vs 0) and gastrointestinal (5 [1-18] vs 0 [0-2])prescriptions. Median (IQR) differences specifically in neurodevelopmental (neurological prescriptions: 42 [22-64] vs 0 [0-3]) and pediatric intensive care unit (total cost prescriptions: \u00a31045 [\u00a3244-\u00a31914] vs \u00a338 [\u00a314-\u00a3220]) settings were observed. While a genetic diagnosis was associated with sustained and intensive health care utilization during the study period, it was also associated with a shift toward targeted, condition-specific medical care.<\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n In this cohort study, a WGS diagnosis was associated with the integration of specialist care and the alignment of health care resources to support specific needs of children with complex disorders. These findings suggest that while longitudinal health care utilization remains intensive following a genetic diagnosis, identifying these conditions is important for accurately mapping and managing the downstream clinical resource requirements of this population.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2026.34372","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T15:00:30Z","timestamp":1789657230000},"page":"e2634372","source":"Crossref","is-referenced-by-count":0,"title":["Diagnosis Through Whole Genome Sequencing and Care Utilization in Children With Severe Illness"],"prefix":"10.1001","volume":"9","author":[{"given":"Joao M. L.","family":"Dias","sequence":"first","affiliation":[{"name":"Department of Paediatrics, University of Cambridge, School of Clinical Medicine, Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravi P.","family":"More","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, University of Cambridge, School of Clinical Medicine, Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duncan","family":"Butler","sequence":"additional","affiliation":[{"name":"Prescribing Services Ltd, Norfolk, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian","family":"Brown","sequence":"additional","affiliation":[{"name":"Litcham Health Centre, Norfolk, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Courtney E.","family":"French","sequence":"additional","affiliation":[{"name":"Children\u2019s Rare Disease Collaborative, Boston Children\u2019s Hospital, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Dolling","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, University of Cambridge, School of Clinical Medicine, Cambridge, United Kingdom"},{"name":"Department of Psychology, University of Cambridge, Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F. Lucy","family":"Raymond","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, University of Cambridge, School of Clinical Medicine, Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David H.","family":"Rowitch","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, University of Cambridge, School of Clinical Medicine, Cambridge, United Kingdom"},{"name":"Departments of Pediatrics, Cedars-Sinai Guerin Children\u2019s, Los Angeles, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine E.","family":"Aiken","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, University of Cambridge, School of Clinical Medicine, Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","published-online":{"date-parts":[[2026,9,17]]},"reference":[{"issue":"2","key":"zoi260931r1","doi-asserted-by":"publisher","first-page":"e331","DOI":"10.1016\/S2214-109X(23)00537-5","article-title":"A research definition and framework for acute paediatric critical illness across resource-variable settings: a modified Delphi consensus.","volume":"12","author":"Arias","year":"2024","journal-title":"Lancet Glob Health"},{"issue":"1","key":"zoi260931r2","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1186\/s12887-023-04254-0","article-title":"Impact of prematurity on long-stay paediatric intensive care unit admissions in England 2008-2018.","volume":"23","author":"van Hasselt","year":"2023","journal-title":"BMC Pediatr"},{"issue":"6","key":"zoi260931r3","doi-asserted-by":"publisher","first-page":"903","DOI":"10.1016\/j.aucc.2024.05.001","article-title":"Neurodevelopmental outcome and quality of life in children admitted to the paediatric intensive care unit: a single-centre Australian cohort study.","volume":"37","author":"Long","year":"2024","journal-title":"Aust Crit Care"},{"issue":"8","key":"zoi260931r4","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1097\/PCC.0000000000003522","article-title":"Rapid whole-genome sequencing and clinical management in the PICU: a multicenter cohort, 2016-2023.","volume":"25","author":"Rodriguez","year":"2024","journal-title":"Pediatr Crit Care Med"},{"issue":"11","key":"zoi260931r5","doi-asserted-by":"publisher","first-page":"1529","DOI":"10.1038\/s41431-020-0667-z","article-title":"Delivering genome sequencing for rapid genetic diagnosis in critically ill children: parent and professional views, experiences and challenges.","volume":"28","author":"Hill","year":"2020","journal-title":"Eur J Hum Genet"},{"issue":"4","key":"zoi260931r6","doi-asserted-by":"publisher","first-page":"429","DOI":"10.3390\/children12040429","article-title":"Rapid whole-genome sequencing in critically ill infants and children with suspected, undiagnosed genetic diseases: evolution to a first-tier clinical laboratory test in the era of precision medicine.","volume":"12","author":"Kansal","year":"2025","journal-title":"Children (Basel)"},{"issue":"11","key":"zoi260931r7","doi-asserted-by":"publisher","first-page":"1007","DOI":"10.1097\/PCC.0000000000002056","article-title":"Rapid whole genome sequencing has clinical utility in children in the PICU.","volume":"20","author":"Sanford","year":"2019","journal-title":"Pediatr Crit Care Med"},{"issue":"1","key":"zoi260931r8","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1038\/s41525-024-00404-0","article-title":"Rapid genomic sequencing for genetic disease diagnosis and therapy in intensive care units: a review.","volume":"9","author":"Kingsmore","year":"2024","journal-title":"NPJ Genom Med"},{"issue":"1","key":"zoi260931r9","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1038\/s41525-018-0045-8","article-title":"The NSIGHT1-randomized controlled trial: rapid whole-genome sequencing for accelerated etiologic diagnosis in critically ill infants.","volume":"3","author":"Petrikin","year":"2018","journal-title":"NPJ Genom Med"},{"issue":"11","key":"zoi260931r10","doi-asserted-by":"publisher","first-page":"755","DOI":"10.1038\/s41576-023-00621-w","article-title":"Genomic newborn screening for rare diseases.","volume":"24","author":"Stark","year":"2023","journal-title":"Nat Rev Genet"},{"issue":"12","key":"zoi260931r11","doi-asserted-by":"publisher","first-page":"1611","DOI":"10.1038\/s41372-019-0451-5","article-title":"Infant mortality: the contribution of genetic disorders.","volume":"39","author":"Wojcik","year":"2019","journal-title":"J Perinatol"},{"issue":"5","key":"zoi260931r12","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1007\/s00134-019-05552-x","article-title":"Whole genome sequencing reveals that genetic conditions are frequent in intensively ill children.","volume":"45","author":"French","year":"2019","journal-title":"Intensive Care Med"},{"issue":"2","key":"zoi260931r13","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1515\/medgen-2023-2015","article-title":"Diagnostic genomic sequencing in critically ill children.","volume":"35","author":"Auber","year":"2023","journal-title":"Med Genet"},{"key":"zoi260931r14","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1038\/s41525-018-0049-4","article-title":"Rapid whole-genome sequencing decreases infant morbidity and cost of hospitalization.","volume":"3","author":"Farnaes","year":"2018","journal-title":"NPJ Genom Med"},{"issue":"4","key":"zoi260931r15","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1001\/jamaneurol.2022.0067","article-title":"Multicenter consensus approach to evaluation of neonatal hypotonia in the genomic era: a review.","volume":"79","author":"Morton","year":"2022","journal-title":"JAMA Neurol"},{"key":"zoi260931r16","doi-asserted-by":"publisher","DOI":"10.1038\/s41390-025-04691-w","article-title":"Neonatal neurocritical care considerations for prenatally identified neurological disorders.","author":"Gano","year":"2026","journal-title":"Pediatr Res"},{"issue":"3","key":"zoi260931r17","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1136\/archdischild-2023-325970","article-title":"Paediatric intensive care admissions of preterm children born <32 weeks gestation: a national retrospective cohort study using data linkage.","volume":"109","author":"van Hasselt","year":"2024","journal-title":"Arch Dis Child Fetal Neonatal Ed"},{"issue":"3","key":"zoi260931r19","doi-asserted-by":"publisher","first-page":"e304","DOI":"10.1097\/PCC.0000000000003668","article-title":"Hospital-acquired complications in critically ill children and PICU length of stay, duration of respiratory support, and economics: propensity score matching in a single-center cohort, 2015-2020.","volume":"26","author":"Schults","year":"2025","journal-title":"Pediatr Crit Care Med"},{"issue":"7","key":"zoi260931r21","doi-asserted-by":"publisher","first-page":"1231","DOI":"10.1016\/j.ajhg.2021.05.008","article-title":"Project Baby Bear: rapid precision care incorporating rWGS in 5 California children\u2019s hospitals demonstrates improved clinical outcomes and reduced costs of care.","volume":"108","author":"Dimmock","year":"2021","journal-title":"Am J Hum Genet"},{"issue":"2","key":"zoi260931r22","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1001\/jama.2023.9350","article-title":"Rapid whole-genomic sequencing and a targeted neonatal gene panel in infants with a suspected genetic disorder.","volume":"330","author":"Maron","year":"2023","journal-title":"JAMA"},{"issue":"12","key":"zoi260931r23","doi-asserted-by":"publisher","first-page":"1218","DOI":"10.1001\/jamapediatrics.2021.3496","article-title":"Effect of whole-genome sequencing on the clinical management of acutely ill infants with suspected genetic disease: a randomized clinical trial.","volume":"175","author":"Krantz","year":"2021","journal-title":"JAMA Pediatr"},{"issue":"9","key":"zoi260931r25","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2022.104571","article-title":"Rapid exome sequencing in critically ill children impacts acute and long-term management of patients and their families: a retrospective regional evaluation.","volume":"65","author":"McDermott","year":"2022","journal-title":"Eur J Med Genet"},{"issue":"4","key":"zoi260931r26","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1136\/archdischild-2024-327457","article-title":"Transition from neonatal to paediatric intensive care of very preterm-born children: a cohort study of children born between 2013 and 2018 in England and Wales.","volume":"110","author":"van Hasselt","year":"2025","journal-title":"Arch Dis Child Fetal Neonatal Ed"},{"issue":"3","key":"zoi260931r28","doi-asserted-by":"publisher","DOI":"10.1016\/j.xhgg.2022.100113","article-title":"Refinements and considerations for trio whole-genome sequence analysis when investigating Mendelian diseases presenting in early childhood.","volume":"3","author":"French","year":"2022","journal-title":"HGG Adv"},{"key":"zoi260931r30","doi-asserted-by":"publisher","first-page":"k1687","DOI":"10.1136\/bmj.k1687","article-title":"The 100?000 Genomes Project: bringing whole genome sequencing to the NHS.","volume":"361","author":"Turnbull","year":"2018","journal-title":"BMJ"},{"issue":"10","key":"zoi260931r31","doi-asserted-by":"publisher","first-page":"1674","DOI":"10.1097\/CCM.0000000000005052","article-title":"Application of full-spectrum rapid clinical genome sequencing improves diagnostic rate and clinical outcomes in critically ill infants in the China Neonatal Genomes Project.","volume":"49","author":"Wu","year":"2021","journal-title":"Crit Care Med"},{"issue":"D1","key":"zoi260931r33","doi-asserted-by":"publisher","first-page":"D938","DOI":"10.1093\/nar\/gkad1082","article-title":"The Monarch Initiative in 2024: an analytic platform integrating phenotypes, genes and diseases across species.","volume":"52","author":"Putman","year":"2024","journal-title":"Nucleic Acids Res"},{"issue":"8","key":"zoi260931r34","doi-asserted-by":"publisher","first-page":"774","DOI":"10.1016\/S0895-4356(01)00341-9","article-title":"Internal validation of predictive models: efficiency of some procedures for logistic regression analysis.","volume":"54","author":"Steyerberg","year":"2001","journal-title":"J Clin Epidemiol"},{"key":"zoi260931r35","doi-asserted-by":"publisher","first-page":"b605","DOI":"10.1136\/bmj.b605","article-title":"Prognosis and prognostic research: validating a prognostic model.","volume":"338","author":"Altman","year":"2009","journal-title":"BMJ"},{"issue":"2","key":"zoi260931r36","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1038\/s41431-025-01987-7","article-title":"Fathers\u2019 and mothers\u2019 support needs and support experiences after rapid genome sequencing.","volume":"34","author":"Dolling","year":"2026","journal-title":"Eur J Hum Genet"},{"key":"zoi260931r18","author":"Choi","year":"2023"},{"key":"zoi260931r20","volume-title":"Preterm Birth and Paediatric Intensive Care: Using National Data to Examine Critical Illness in Early Childhood","author":"van Hasselt","year":"2024"},{"key":"zoi260931r29","author":"Redman"},{"key":"zoi260931r37","volume-title":"Psychosocial Impact of Paediatric Early Rapid Genomic Testing and Diagnosis: A Mixed Methods Study of Parental Adjustment, Adaptation, Risk and Resilience","author":"Dolling","year":"2025"},{"key":"zoi260931r24","unstructured":"Michigan: Project Baby Deer. Radys Children\u2019s Institute for Genomic Medicine. Accessed September 10, 2025. https:\/\/radygenomics.org\/case-studies\/michigan-project-baby-deer\/"},{"key":"zoi260931r27","unstructured":"ECLIPSE. Prescribing Services Ltd. Accessed December 3, 2025. https:\/\/www.eclipselive.org"},{"key":"zoi260931r32","unstructured":"National Genomic Test Directory. National Health Service England. Updated July 16, 2026. Accessed March 4, 2026. https:\/\/www.england.nhs.uk\/publication\/national-genomic-test-directories\/"}],"container-title":["JAMA Network Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/articlepdf\/2854183\/dias_2026_oi_260931_1788979037.53386.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T15:00:33Z","timestamp":1789657233000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/fullarticle\/2854183"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,17]]},"references-count":37,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,9,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamanetworkopen.2026.34372","relation":{},"ISSN":["2574-3805"],"issn-type":[{"value":"2574-3805","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,17]]}}}