{"id":"https://openalex.org/W7204848747","doi":"https://doi.org/10.64898/2026.08.28.26361655","title":"A Multi-Agent Large Language Model Reasoning Engine for Early Detection of Pediatric Growth Disorders","display_name":"A Multi-Agent Large Language Model Reasoning Engine for Early Detection of Pediatric Growth Disorders","publication_year":2026,"publication_date":"2026-08-31","ids":{"openalex":"https://openalex.org/W7204848747","doi":"https://doi.org/10.64898/2026.08.28.26361655"},"language":"en","primary_location":{"id":"doi:10.64898/2026.08.28.26361655","doi":"https://doi.org/10.64898/2026.08.28.26361655","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.08.28.26361655","pdf_url":"https://www.medrxiv.org/content/medrxiv/early/2026/08/31/2026.08.28.26361655.full.pdf","source":{"id":"https://openalex.org/S3005729997","display_name":"medRxiv","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core"],"host_organization":null,"host_organization_name":null,"host_organization_lineage":["https://openalex.org/P4310315909"],"host_organization_lineage_names":["Cold Spring Harbor Laboratory Press"],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"medRxiv","raw_type":"posted-content"},"volume":null,"type":"preprint","is_traditional":true,"indexed_in":["crossref"],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://www.medrxiv.org/content/medrxiv/early/2026/08/31/2026.08.28.26361655.full.pdf","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5013655852","display_name":"Naveed Rabbani","orcid":"https://orcid.org/0000-0002-9769-4437","observed_orcids":["https://orcid.org/0000-0002-9769-4437"]},"institutions":[{"id":"https://openalex.org/I136199984","display_name":"Harvard University","ror":"https://ror.org/03vek6s52","country_code":"US","type":"education","lineage":["https://openalex.org/I136199984"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Naveed Rabbani","raw_affiliation_strings":["Harvard Medical School;"],"raw_orcid":"https://orcid.org/0000-0002-9769-4437","affiliations":[{"raw_affiliation_string":"Harvard Medical School;","institution_ids":["https://openalex.org/I136199984"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5118139475","display_name":"Jannik Mettner","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I136199984","display_name":"Harvard University","ror":"https://ror.org/03vek6s52","country_code":"US","type":"education","lineage":["https://openalex.org/I136199984"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Jannik Mettner","raw_affiliation_strings":["Harvard Medical School;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Harvard Medical School;","institution_ids":["https://openalex.org/I136199984"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5010168205","display_name":"Kyungjoon Lee","orcid":"https://orcid.org/0000-0002-4026-476X","observed_orcids":["https://orcid.org/0000-0002-4026-476X"]},"institutions":[{"id":"https://openalex.org/I136199984","display_name":"Harvard University","ror":"https://ror.org/03vek6s52","country_code":"US","type":"education","lineage":["https://openalex.org/I136199984"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Kyungjoon Lee","raw_affiliation_strings":["Harvard Medical School;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Harvard Medical School;","institution_ids":["https://openalex.org/I136199984"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5034023552","display_name":"Carmen L. Soto-Rivera","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I136199984","display_name":"Harvard University","ror":"https://ror.org/03vek6s52","country_code":"US","type":"education","lineage":["https://openalex.org/I136199984"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Carmen L. Soto-Rivera","raw_affiliation_strings":["Harvard Medical School;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Harvard Medical School;","institution_ids":["https://openalex.org/I136199984"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5148782132","display_name":"Alexander Windberger","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I41121874","display_name":"Heilbronn University","ror":"https://ror.org/04g5gcg95","country_code":"DE","type":"education","lineage":["https://openalex.org/I41121874"]}],"countries":["DE"],"is_corresponding":false,"raw_author_name":"Alexander Windberger","raw_affiliation_strings":["Heilbronn University of Applied Sciences;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Heilbronn University of Applied Sciences;","institution_ids":["https://openalex.org/I41121874"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5119025822","display_name":"Karl Santiago","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I136199984","display_name":"Harvard University","ror":"https://ror.org/03vek6s52","country_code":"US","type":"education","lineage":["https://openalex.org/I136199984"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Karl Santiago","raw_affiliation_strings":["Harvard Medical School;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Harvard Medical School;","institution_ids":["https://openalex.org/I136199984"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5020695759","display_name":"Jonathan Hatoun","orcid":"https://orcid.org/0000-0002-1146-5159","observed_orcids":["https://orcid.org/0000-0002-1146-5159"]},"institutions":[{"id":"https://openalex.org/I136199984","display_name":"Harvard University","ror":"https://ror.org/03vek6s52","country_code":"US","type":"education","lineage":["https://openalex.org/I136199984"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Jonathan Hatoun","raw_affiliation_strings":["Harvard Medical School;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Harvard Medical School;","institution_ids":["https://openalex.org/I136199984"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5010596517","display_name":"Emily Trudell Correa","orcid":"https://orcid.org/0000-0003-1985-405X","observed_orcids":["https://orcid.org/0000-0003-1985-405X"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Emily Trudell Correa","raw_affiliation_strings":["Pediatric Physicians' Organization at Children's"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Pediatric Physicians' Organization at Children's","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5002114430","display_name":"Louis Vernacchio","orcid":"https://orcid.org/0000-0002-2012-5404","observed_orcids":["https://orcid.org/0000-0002-2012-5404"]},"institutions":[{"id":"https://openalex.org/I136199984","display_name":"Harvard University","ror":"https://ror.org/03vek6s52","country_code":"US","type":"education","lineage":["https://openalex.org/I136199984"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Louis Vernacchio","raw_affiliation_strings":["Harvard Medical School;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Harvard Medical School;","institution_ids":["https://openalex.org/I136199984"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5088509061","display_name":"Isaac S. Kohane","orcid":"https://orcid.org/0000-0003-2192-5160","observed_orcids":["https://orcid.org/0000-0003-2192-5160"]},"institutions":[{"id":"https://openalex.org/I136199984","display_name":"Harvard University","ror":"https://ror.org/03vek6s52","country_code":"US","type":"education","lineage":["https://openalex.org/I136199984"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Isaac Kohane","raw_affiliation_strings":["Harvard Medical School;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Harvard Medical School;","institution_ids":["https://openalex.org/I136199984"]}]}],"institutions":[],"countries_distinct_count":2,"institutions_distinct_count":2,"corresponding_author_ids":["https://openalex.org/A5013655852"],"corresponding_institution_ids":["https://openalex.org/I136199984"],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":true,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T13702","display_name":"Machine Learning in Healthcare","score":0.8330000042915344,"subfield":{"id":"https://openalex.org/subfields/1702","display_name":"Artificial Intelligence"},"field":{"id":"https://openalex.org/fields/17","display_name":"Computer Science"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},"topics":[{"id":"https://openalex.org/T13702","display_name":"Machine Learning in Healthcare","score":0.8330000042915344,"subfield":{"id":"https://openalex.org/subfields/1702","display_name":"Artificial Intelligence"},"field":{"id":"https://openalex.org/fields/17","display_name":"Computer Science"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},{"id":"https://openalex.org/T11636","display_name":"Artificial Intelligence in Healthcare and Education","score":0.13169999420642853,"subfield":{"id":"https://openalex.org/subfields/2718","display_name":"Health Informatics"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T11396","display_name":"Artificial Intelligence in Healthcare","score":0.022600000724196434,"subfield":{"id":"https://openalex.org/subfields/3605","display_name":"Health Information Management"},"field":{"id":"https://openalex.org/fields/36","display_name":"Health Professions"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/pediatric-growth-disorders","display_name":"pediatric growth disorders","score":0.9890000224113464},{"id":"https://openalex.org/keywords/early-detection","display_name":"early detection","score":0.7319999933242798},{"id":"https://openalex.org/keywords/multi-agent-large-language-models","display_name":"multi-agent large language models","score":0.8939999938011169},{"id":"https://openalex.org/keywords/differential-diagnosis","display_name":"differential diagnosis","score":0.7609999775886536},{"id":"https://openalex.org/keywords/electronic-health-records","display_name":"electronic health records","score":0.777999997138977},{"id":"https://openalex.org/keywords/longitudinal-growth-patterns","display_name":"longitudinal growth patterns","score":0.6460000276565552},{"id":"https://openalex.org/keywords/type-1-diabetes","display_name":"type 1 diabetes","score":0.8460000157356262},{"id":"https://openalex.org/keywords/pituitary-disorders","display_name":"pituitary disorders","score":0.9929999709129333},{"id":"https://openalex.org/keywords/celiac-disease","display_name":"celiac disease","score":1.0},{"id":"https://openalex.org/keywords/delayed-diagnosis","display_name":"delayed diagnosis","score":0.8740000128746033},{"id":"https://openalex.org/keywords/clinical-decision-support","display_name":"clinical decision support","score":0.906000018119812},{"id":"https://openalex.org/keywords/sprouts","display_name":"sprouts","score":0.7599999904632568}],"concepts":[{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.6570000052452087},{"id":"https://openalex.org/C22467394","wikidata":"https://www.wikidata.org/wiki/Q849359","display_name":"Multidisciplinary approach","level":2,"score":0.48809999227523804},{"id":"https://openalex.org/C2780801072","wikidata":"https://www.wikidata.org/wiki/Q837512","display_name":"Differential diagnosis","level":2,"score":0.42579999566078186},{"id":"https://openalex.org/C3020672099","wikidata":"https://www.wikidata.org/wiki/Q857354","display_name":"Longitudinal data","level":2,"score":0.4081000089645386},{"id":"https://openalex.org/C2779134260","wikidata":"https://www.wikidata.org/wiki/Q12136","display_name":"Disease","level":2,"score":0.4074000120162964},{"id":"https://openalex.org/C195910791","wikidata":"https://www.wikidata.org/wiki/Q1324077","display_name":"Medical record","level":2,"score":0.3930000066757202},{"id":"https://openalex.org/C534262118","wikidata":"https://www.wikidata.org/wiki/Q177719","display_name":"Medical diagnosis","level":2,"score":0.3864000141620636},{"id":"https://openalex.org/C187212893","wikidata":"https://www.wikidata.org/wiki/Q123028","display_name":"Pediatrics","level":1,"score":0.36399999260902405},{"id":"https://openalex.org/C2984752397","wikidata":"https://www.wikidata.org/wiki/Q3259956","display_name":"Primary care","level":2,"score":0.3441999852657318},{"id":"https://openalex.org/C2780463512","wikidata":"https://www.wikidata.org/wiki/Q15122700","display_name":"Trainer","level":2,"score":0.3314000070095062},{"id":"https://openalex.org/C3020132585","wikidata":"https://www.wikidata.org/wiki/Q2671652","display_name":"Diagnostic accuracy","level":2,"score":0.3222000002861023},{"id":"https://openalex.org/C2779473830","wikidata":"https://www.wikidata.org/wiki/Q1540899","display_name":"MEDLINE","level":2,"score":0.3192000091075897},{"id":"https://openalex.org/C19527891","wikidata":"https://www.wikidata.org/wiki/Q1120908","display_name":"Medical physics","level":1,"score":0.3190000057220459},{"id":"https://openalex.org/C58471807","wikidata":"https://www.wikidata.org/wiki/Q327120","display_name":"Receiver operating characteristic","level":2,"score":0.31790000200271606},{"id":"https://openalex.org/C21200559","wikidata":"https://www.wikidata.org/wiki/Q7451068","display_name":"Sensitivity (control systems)","level":2,"score":0.29989999532699585},{"id":"https://openalex.org/C154945302","wikidata":"https://www.wikidata.org/wiki/Q11660","display_name":"Artificial intelligence","level":1,"score":0.29330000281333923},{"id":"https://openalex.org/C82157600","wikidata":"https://www.wikidata.org/wiki/Q2671652","display_name":"Diagnostic test","level":2,"score":0.2784000039100647},{"id":"https://openalex.org/C2777895361","wikidata":"https://www.wikidata.org/wiki/Q1758614","display_name":"Longitudinal study","level":2,"score":0.27799999713897705},{"id":"https://openalex.org/C119857082","wikidata":"https://www.wikidata.org/wiki/Q2539","display_name":"Machine learning","level":1,"score":0.27320000529289246},{"id":"https://openalex.org/C4554734","wikidata":"https://www.wikidata.org/wiki/Q593744","display_name":"Knowledge base","level":2,"score":0.262800008058548},{"id":"https://openalex.org/C2983335520","wikidata":"https://www.wikidata.org/wiki/Q47537570","display_name":"Growth model","level":2,"score":0.2506999969482422}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.64898/2026.08.28.26361655","doi":"https://doi.org/10.64898/2026.08.28.26361655","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.08.28.26361655","pdf_url":"https://www.medrxiv.org/content/medrxiv/early/2026/08/31/2026.08.28.26361655.full.pdf","source":{"id":"https://openalex.org/S3005729997","display_name":"medRxiv","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core"],"host_organization":null,"host_organization_name":null,"host_organization_lineage":["https://openalex.org/P4310315909"],"host_organization_lineage_names":["Cold Spring Harbor Laboratory Press"],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"medRxiv","raw_type":"posted-content"}],"best_oa_location":{"id":"doi:10.64898/2026.08.28.26361655","doi":"https://doi.org/10.64898/2026.08.28.26361655","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.08.28.26361655","pdf_url":"https://www.medrxiv.org/content/medrxiv/early/2026/08/31/2026.08.28.26361655.full.pdf","source":{"id":"https://openalex.org/S3005729997","display_name":"medRxiv","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core"],"host_organization":null,"host_organization_name":null,"host_organization_lineage":["https://openalex.org/P4310315909"],"host_organization_lineage_names":["Cold Spring Harbor Laboratory Press"],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"medRxiv","raw_type":"posted-content"},"sustainable_development_goals":[{"score":0.9763000011444092,"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3"}],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":true,"grobid_xml":true},"content_urls":{"pdf":"https://content.openalex.org/works/W7204848747.pdf","grobid_xml":"https://content.openalex.org/works/W7204848747.grobid-xml"},"referenced_works_count":1,"referenced_works":["https://openalex.org/W4417175683"],"related_works":["https://openalex.org/W7162056570","https://openalex.org/W2911462778","https://openalex.org/W2005214527","https://openalex.org/W7168402073","https://openalex.org/W2888443876","https://openalex.org/W2269890056","https://openalex.org/W7166575230","https://openalex.org/W7112712498","https://openalex.org/W4411272297","https://openalex.org/W4384133705"],"abstract_inverted_index":{"Routine":[0],"childhood":[1],"growth":[2,99],"surveillance":[3],"is":[4],"a":[5,43,55,74,87,91,106,114,123,132,141,164,278,303],"cornerstone":[6],"of":[7,17,58,109,167,195,224,253,281],"pediatric":[8,59,76,168,284,312],"care.":[9,313],"Growth":[10],"pattern":[11],"abnormalities":[12,22],"are":[13,23],"often":[14],"early":[15],"manifestations":[16],"chronic":[18],"disease.":[19,268],"Yet":[20],"subtle":[21],"frequently":[24],"underrecognized,":[25],"leading":[26,145],"to":[27,53,112,147,192,199,246,276,287],"diagnostic":[28,235,309],"delays":[29,310],"and":[30,83,159,180,183,264],"avoidable":[31],"morbidity.":[32],"We":[33],"introduce":[34],"SPROUT":[35,85,152,270],"(System":[36],"for":[37,218,255,261,266,307],"Pediatric":[38],"Recognition":[39],"Of":[40],"Undiagnosed":[41],"Trajectories),":[42],"generalized,":[44],"multi-agent":[45,271],"large":[46,75],"language":[47],"model":[48,154],"(LLM)":[49],"reasoning":[50,121],"system":[51,250,272],"designed":[52],"identify":[54],"broad":[56],"spectrum":[57],"growth-related":[60,283],"conditions":[61,238,285],"from":[62],"longitudinal":[63,98,189],"electronic":[64],"health":[65],"records":[66],"(EHRs)":[67],"earlier":[68],"than":[69],"standard":[70],"clinical":[71,247,291],"practice.":[72],"Using":[73],"primary":[77,169],"care":[78,170],"EHR":[79],"dataset,":[80],"we":[81],"developed":[82],"validated":[84],"as":[86,302],"two-stage":[88],"system.":[89],"First,":[90],"highly":[92],"specific":[93],"LLM":[94,110],"screener":[95,153,208],"flags":[96],"concerning":[97],"patterns.":[100],"Second,":[101],"an":[102],"Orchestrator":[103],"module":[104,125],"coordinates":[105],"multidisciplinary":[107],"panel":[108,130,213],"agents":[111],"generate":[113],"ranked":[115],"differential":[116],"diagnosis.":[117,196],"To":[118],"correct":[119],"systemic":[120],"errors,":[122],"Trainer":[124],"injects":[126],"meta-knowledge":[127],"into":[128],"the":[129,148,177,193,207,234,249,274],"via":[131],"dedicated":[133],"\"Learner\"":[134],"agent.":[135],"Diagnostic":[136],"capability":[137],"was":[138],"evaluated":[139,173,187],"using":[140,188],"walk-forward,":[142],"visit-by-visit":[143],"simulation":[144],"up":[146,191],"diagnosis":[149],"date.":[150],"The":[151,269],"achieved":[155,251],"98%":[156],"(83/85)":[157],"specificity":[158,182],"28%":[160],"(9/32)":[161],"sensitivity":[162,185],"on":[163,231],"gold-standard":[165],"dataset":[166],"patients":[171,202],"when":[172,186],"one":[174],"year":[175,244],"before":[176,240,289],"index":[178],"date,":[179],"100%":[181],"47%":[184],"data":[190],"day":[194],"When":[197],"applied":[198],"300":[200],"control":[201],"(i.e.,":[203],"healthy":[204],"or":[205],"undiagnosed),":[206],"flagged":[209],"15.":[210],"Subsequent":[211],"expert":[212],"review":[214],"confirmed":[215],"high":[216],"suspicion":[217],"undiagnosed":[219],"pathology":[220],"in":[221,311],"33%":[222],"(5/15)":[223],"these":[225],"cases.":[226],"In":[227],"chronological":[228],"walk-forward":[229],"validation":[230],"disease":[232],"cases,":[233],"engine":[236],"identified":[237],"well":[239],"standard-of-care":[241],"documentation.":[242],"One":[243],"prior":[245],"diagnosis,":[248],"sensitivities":[252],"81%":[254],"type":[256],"1":[257],"diabetes":[258],"mellitus,":[259],"56%":[260],"pituitary":[262],"disorders,":[263],"44%":[265],"celiac":[267],"demonstrates":[273],"ability":[275],"detect":[277],"significant":[279],"portion":[280],"latent":[282],"months":[286],"years":[288],"current":[290],"standards":[292],"while":[293],"minimizing":[294],"false":[295],"positives.":[296],"These":[297],"results":[298],"support":[299,305],"its":[300],"potential":[301],"decision":[304],"tool":[306],"reducing":[308]},"counts_by_year":[],"updated_date":"2026-11-04T10:54:05.112534","created_date":"2026-09-01T00:00:00"}
