Congenital TORCH Infections and Neurodevelopmental Outcomes

Abstract

Importance 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. Objective 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. Design, Setting, and Participants 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 ‎2025 to July 2026. Exposure Clinically diagnosed congenital TORCH infections, identified from national registers, including cytomegalovirus, Toxoplasma gondii , rubella, and herpes simplex viruses. Main Outcomes and Measures 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. Results Among 3 666 002 individuals born in Sweden, including 3 665 027 individuals without TORCH infections (1 883 911 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 = −1.50 points; 95% CI, −2.60 to −0.40 points). Conclusions and Relevance 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.