{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T03:34:36Z","timestamp":1790048076128,"version":"4.0.1"},"reference-count":30,"publisher":"American Medical Association (AMA)","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Pediatr"],"abstract":"\n Importance<\/jats:title>\n Congenital TORCH (toxoplasmosis, syphilis, rubella, cytomegalovirus, or herpes simplex) infections are established causes of severe fetal injury, yet their population-level contribution to neurodevelopmental and psychiatric outcomes, independent of familial confounding, remains yet to be quantified.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To investigate whether congenital TORCH infections are associated with neurodevelopmental and psychiatric outcomes, including autism and intellectual disability, as well as academic performance, using population-based and sibling-controlled analyses.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This nationwide, population-based cohort study with sibling comparisons was conducted using linked data from Swedish national health, birth, insurance, education, and death registers. Individuals born in Sweden between 1987 and 2021, including individuals diagnosed with a congenital TORCH infection, were included. Full siblings were identified for within-family comparisons. Individuals were followed up from birth until death, emigration, or December 31, 2023. Data were analyzed from November \u200e2025 to July 2026.<\/jats:p>\n <\/jats:sec>\n \n Exposure<\/jats:title>\n \n Clinically diagnosed congenital TORCH infections, identified from national registers, including cytomegalovirus,\n Toxoplasma gondii<\/jats:italic>\n , rubella, and herpes simplex viruses.\n <\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n Autism (with and without co-occurring intellectual disability), intellectual disability (by severity), attention-deficit\/hyperactivity disorder, obsessive-compulsive disorder, Tourette and chronic tic disorders, nonaffective psychosis, and standardized school grades at age 16 years were assessed. Associations were estimated with hazard ratios (HRs) using Cox regression and sibling-comparison models.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Among 3\u202f666\u202f002 individuals born in Sweden, including 3\u202f665\u202f027 individuals without TORCH infections (1\u202f883\u202f911 male [51.4%]; mean [SD] follow-up, 20.50 [11.15] years) and 975 individuals with TORCH infections (532 male [54.6%]; mean [SD] follow-up, 18.70 [10.39] years), congenital TORCH infections were associated with increased risks of intellectual disability (HR, 7.22; 95% CI, 6.14-8.49) and autism (HR, 3.10; 95% CI, 2.55-3.76), with similar or greater HRs in sibling comparisons (intellectual disability: HR, 11.28; 95% CI, 5.97-21.33; autism: HR, 3.19; 95% CI, 1.97-5.15). Risks increased with greater severity of intellectual disability, with HRs ranging from 3.01; 95% CI, 2.21-4.11 for mild to 23.51; 95% CI, 18.06-30.60 for severe to profound intellectual disability) and were greater for autism with (HR, 6.23; 95% CI, 4.69-8.28) vs without (HR, 1.97; 95% CI, 1.51-2.57) co-occurring intellectual disability. No consistent associations were observed for obsessive-compulsive disorder, and associations with attention-deficit\/hyperactivity disorder attenuated in sibling analyses. Individuals who were exposed had lower school grades in adolescence (TORCH-associated decrease\u2009=\u2009\u22121.50 points; 95% CI, \u22122.60 to \u22120.40 points).<\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n In this study, congenital TORCH infections were rare but associated with intellectual disability and autism, with evidence of broader associated cognitive outcomes extending beyond diagnosed conditions, underscoring the importance of preventing specific vertically transmitted infections.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamapediatrics.2026.4229","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T15:31:05Z","timestamp":1790004665000},"source":"Crossref","is-referenced-by-count":1,"title":["Congenital TORCH Infections and Neurodevelopmental Outcomes"],"prefix":"10.1001","author":[{"given":"Hugo","family":"Sj\u00f6qvist","sequence":"first","affiliation":[{"name":"Department of Global Public Health, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Dalman","sequence":"additional","affiliation":[{"name":"Department of Global Public Health, Karolinska Institutet, Stockholm, Sweden"},{"name":"Centre for Epidemiology and Community Medicine, Region Stockholm, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Mataix-Cols","sequence":"additional","affiliation":[{"name":"Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden"},{"name":"Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rene\u00e9 M.","family":"Gardner","sequence":"additional","affiliation":[{"name":"Department of Global Public Health, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00e5kan","family":"Karlsson","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","published-online":{"date-parts":[[2026,9,21]]},"reference":[{"issue":"1","key":"poi260059r1","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/j.clp.2014.11.001","article-title":"TORCH infections.","volume":"42","author":"Neu","year":"2015","journal-title":"Clin Perinatol"},{"issue":"2","key":"poi260059r2","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1038\/s41579-021-00610-y","article-title":"Infections at the maternal-fetal interface: an overview of pathogenesis and defence.","volume":"20","author":"Megli","year":"2022","journal-title":"Nat Rev Microbiol"},{"issue":"4","key":"poi260059r3","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1016\/S0022-3476(78)80921-4","article-title":"Behavioral consequences of congenital rubella.","volume":"93","author":"Chess","year":"1978","journal-title":"J Pediatr"},{"issue":"9","key":"poi260059r4","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1097\/DBP.0000000000000740","article-title":"Inattention and hyperactivity in children with symptomatic and asymptomatic congenital cytomegalovirus.","volume":"40","author":"Topham","year":"2019","journal-title":"J Dev Behav Pediatr"},{"issue":"6","key":"poi260059r5","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2023-064081","article-title":"Autism spectrum disorder diagnoses and congenital cytomegalovirus.","volume":"153","author":"Pesch","year":"2024","journal-title":"Pediatrics"},{"issue":"7","key":"poi260059r6","doi-asserted-by":"publisher","first-page":"2471","DOI":"10.1038\/s41390-025-04232-5","article-title":"Beyond hearing loss: exploring neurological and neurodevelopmental sequelae in asymptomatic congenital cytomegalovirus infection.","volume":"98","author":"Swanson","year":"2025","journal-title":"Pediatr Res"},{"issue":"10","key":"poi260059r7","doi-asserted-by":"publisher","first-page":"782","DOI":"10.1016\/S2215-0366(22)00264-4","article-title":"Maternal infection during pregnancy and likelihood of autism and intellectual disability in children in Sweden: a negative control and sibling comparison cohort study.","volume":"9","author":"Brynge","year":"2022","journal-title":"Lancet Psychiatry"},{"issue":"8","key":"poi260059r8","doi-asserted-by":"publisher","first-page":"1693","DOI":"10.1017\/S0033291723003604","article-title":"The causal association between maternal depression, anxiety, and infection in pregnancy and neurodevelopmental disorders among 410 461 children: a population study using quasi-negative control cohorts and sibling analysis.","volume":"54","author":"Hope","year":"2024","journal-title":"Psychol Med"},{"issue":"11","key":"poi260059r9","doi-asserted-by":"publisher","first-page":"1023","DOI":"10.1016\/j.biopsych.2022.07.004","article-title":"Prenatal and early childhood infections and subsequent risk of obsessive-compulsive disorder and tic disorders: a nationwide, sibling-controlled study.","volume":"93","author":"Zhang","year":"2023","journal-title":"Biol Psychiatry"},{"issue":"7","key":"poi260059r10","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1016\/S2352-4642(26)00045-3","article-title":"Familial confounding and causal inference in child and adolescent neurodevelopment and mental health.","volume":"10","author":"Mataix-Cols","year":"2026","journal-title":"Lancet Child Adolesc Health"},{"issue":"8","key":"poi260059r11","doi-asserted-by":"publisher","first-page":"e357","DOI":"10.1111\/j.1651-2227.2012.02711.x","article-title":"Congenital cytomegalovirus infection\u2014a common cause of hearing loss of unknown aetiology.","volume":"101","author":"Karltorp","year":"2012","journal-title":"Acta Paediatr"},{"issue":"3","key":"poi260059r12","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1007\/s10654-025-01356-0","article-title":"Moving beyond risk ratios in sibling analysis: estimating clinically useful measures from family-based analysis.","volume":"41","author":"Ahlqvist","year":"2026","journal-title":"Eur J Epidemiol"},{"issue":"6900","key":"poi260059r13","doi-asserted-by":"publisher","first-page":"1113","DOI":"10.1016\/S0140-6736(55)92951-2","article-title":"Rubella as a cause of mental deficiency.","volume":"269","author":"Kirman","year":"1955","journal-title":"Lancet"},{"key":"poi260059r14","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1016\/B978-0-444-64029-1.00006-0","article-title":"Congenital and perinatal infections.","volume":"162","author":"Ostrander","year":"2019","journal-title":"Handb Clin Neurol"},{"issue":"1","key":"poi260059r15","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1007\/BF01537741","article-title":"Autism in children with congenital rubella.","volume":"1","author":"Chess","year":"1971","journal-title":"J Autism Child Schizophr"},{"key":"poi260059r16","doi-asserted-by":"publisher","first-page":"46483","DOI":"10.1038\/srep46483","article-title":"Sensory defects and developmental delay among children with congenital rubella syndrome.","volume":"7","author":"Toizumi","year":"2017","journal-title":"Sci Rep"},{"issue":"2","key":"poi260059r17","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1007\/BF02409660","article-title":"Autism and congenital cytomegalovirus.","volume":"14","author":"Stubbs","year":"1984","journal-title":"J Autism Dev Disord"},{"issue":"8","key":"poi260059r18","doi-asserted-by":"publisher","first-page":"792","DOI":"10.1111\/apa.13032","article-title":"Prenatal acquired cytomegalovirus infection should be considered in children with autism.","volume":"104","author":"Engman","year":"2015","journal-title":"Acta Paediatr"},{"issue":"3","key":"poi260059r19","doi-asserted-by":"publisher","first-page":"467","DOI":"10.21873\/invivo.11085","article-title":"Prevalence of congenital cytomegalovirus infection assessed through viral genome detection in dried blood spots in children with autism spectrum disorders.","volume":"31","author":"Gentile","year":"2017","journal-title":"In Vivo"},{"issue":"2","key":"poi260059r20","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1016\/j.braindev.2014.03.016","article-title":"Retrospective diagnosis of congenital cytomegalovirus infection in children with autism spectrum disorder but no other major neurologic deficit.","volume":"37","author":"Sakamoto","year":"2015","journal-title":"Brain Dev"},{"issue":"5","key":"poi260059r21","doi-asserted-by":"publisher","first-page":"1483","DOI":"10.1007\/s10803-017-3412-x","article-title":"Congenital cytomegalovirus infection in children with autism spectrum disorder: systematic review and meta-analysis.","volume":"48","author":"Maeyama","year":"2018","journal-title":"J Autism Dev Disord"},{"issue":"5","key":"poi260059r22","doi-asserted-by":"publisher","first-page":"1791","DOI":"10.1038\/s41380-024-02787-z","article-title":"Prenatal and early childhood infections requiring hospitalization and risk of neurodevelopmental disorders in offspring: a population-based birth cohort study in Taiwan.","volume":"30","author":"Lin","year":"2025","journal-title":"Mol Psychiatry"},{"issue":"4","key":"poi260059r23","doi-asserted-by":"publisher","first-page":"1","DOI":"10.58372\/2835-6276.1160","article-title":"Susceptibility of congenital or acquired TORCH-infected children to neurodevelopmental disorders: A cross-sectional study at Cipto Mangunkusumo Hospital, Jakarta, Indonesia: Research Article.","volume":"3","author":"Semiramis","year":"2024","journal-title":"American Journal of Medical and Clinical Research & Reviews"},{"issue":"10","key":"poi260059r24","doi-asserted-by":"publisher","first-page":"1272","DOI":"10.1002\/dneu.22024","article-title":"Epidemiologic studies of exposure to prenatal infection and risk of schizophrenia and autism.","volume":"72","author":"Brown","year":"2012","journal-title":"Dev Neurobiol"},{"issue":"5","key":"poi260059r25","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2017-1517","article-title":"Intelligence and academic achievement with asymptomatic congenital cytomegalovirus infection.","volume":"140","author":"Lopez","year":"2017","journal-title":"Pediatrics"},{"issue":"4","key":"poi260059r26","doi-asserted-by":"publisher","first-page":"584","DOI":"10.1016\/S0022-3476(78)80892-0","article-title":"The longitudinal course of congenital rubella encephalitis in nonretarded children.","volume":"93","author":"Desmond","year":"1978","journal-title":"J Pediatr"},{"key":"poi260059r27","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcv.2020.104518","article-title":"Maternal type of CMV infection and sequelae in infants with congenital CMV: systematic review and meta-analysis.","volume":"129","author":"Maltezou","year":"2020","journal-title":"J Clin Virol"},{"issue":"4","key":"poi260059r28","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1016\/S0095-5108(18)30670-5","article-title":"Should we expand the TORCH complex: a description of clinical and diagnostic aspects of selected old and new agents.","volume":"15","author":"Kinney","year":"1988","journal-title":"Clin Perinatol"},{"key":"poi260059r29","doi-asserted-by":"publisher","DOI":"10.12659\/MSM.947335","article-title":"A review of emerging viral pathogens and current concerns for vertical transmission of infection.","volume":"30","author":"Parums","year":"2024","journal-title":"Med Sci Monit"},{"issue":"10","key":"poi260059r30","doi-asserted-by":"publisher","first-page":"1573","DOI":"10.1093\/infdis\/jiu019","article-title":"Intrauterine growth restriction caused by underlying congenital cytomegalovirus infection.","volume":"209","author":"Pereira","year":"2014","journal-title":"J Infect Dis"}],"container-title":["JAMA Pediatrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamapediatrics\/articlepdf\/2853867\/jamapediatrics_sjqvist_2026_oi_260059_1788290173.39635.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T15:31:05Z","timestamp":1790004665000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamapediatrics\/fullarticle\/2853867"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,21]]},"references-count":30,"URL":"https:\/\/doi.org\/10.1001\/jamapediatrics.2026.4229","relation":{},"ISSN":["2168-6203"],"issn-type":[{"value":"2168-6203","type":"print"}],"subject":[],"published":{"date-parts":[[2026,9,21]]}}}