congenital TORCH Infections and neurodevelopmental outcomes

Congenital TORCH Infections and Neurodevelopmental Outcomes

Overview

• Study Design:
  • nationwide, population-based cohort study with sibling comparisons in Sweden covering births between 1987 and 2021
  • included 3,666,002 individuals (975 with registered congenital TORCH infections and 3,665,027 unexposed controls) followed up through December 31, 2023
• Core Objective:
  • evaluate whether clinically diagnosed congenital TORCH infections (Toxoplasma gondii, rubella, cytomegalovirus [CMV], herpes simplex virus [HSV], syphilis, or other vertical pathogens) are associated with long-term neurodevelopmental and psychiatric outcomes and academic performance, independent of familial confounding

Key Findings

• Intellectual Disability (ID):
  • congenital TORCH exposure was strongly associated with an increased overall risk of ID in adjusted population models (HR 7.22; 95% CI 6.14–8.49) and sibling comparisons (HR 11.28; 95% CI 5.97–21.33)
  • risk increased progressively with ID severity, ranging from mild ID (HR 3.01; 95% CI 2.21–4.11) to severe-to-profound ID (HR 23.51; 95% CI 18.06–30.60)
• Autism Spectrum Disorder:
  • exposed individuals had a significantly elevated risk of autism in both population (HR 3.10; 95% CI 2.55–3.76) and sibling-matched models (HR 3.19; 95% CI 1.97–5.15)
  • risks were markedly higher for autism with co-occurring ID (HR 6.23; 95% CI 4.69–8.28; sibling HR 12.29) than for autism without ID (HR 1.97; 95% CI 1.51–2.57; sibling HR 1.81)
• Other Psychiatric Outcomes:
  • initial population-level associations with ADHD (HR 1.28; 95% CI 1.04–1.57) fully attenuated and lost statistical significance in sibling analyses
  • no consistent associations were observed for obsessive-compulsive disorder (OCD)
• Academic Performance:
  • exposed adolescents without a diagnosis of autism or ID exhibited significantly lower standardized school grades at age 16 years (−1.50 points; 95% CI −2.60 to −0.40 points) compared to unexposed controls

Pathogen-Specific Highlights

• Cytomegalovirus (CMV):
  • accounted for approximately half of all registered TORCH cases (49.9%) and was strongly associated with autism (HR 4.57; 95% CI 3.63–5.75) and ID in both population and sibling analyses
  • associated with a 2.76-point reduction in school grades in sibling models
• Rubella:
  • virtually disappeared in Sweden following national vaccination programs
  • historically exposed individuals demonstrated a marked reduction in teenage academic performance (−5.04 points; 95% CI −8.08 to −2.01 points)

Clinical Practice & Public Health Takeaways

• Direct Teratogenic Impact:
  • the persistence or amplification of hazard ratios in sibling comparisons confirms that observed links to ID and autism are largely driven by direct pathogenetic mechanisms of fetal infection rather than unmeasured shared familial or genetic confounding
• Broader Subclinical Cognitive Deficits:
  • lower academic performance in individuals without overt neurodevelopmental diagnoses indicates that fetal TORCH exposure can cause broader, subclinical cognitive deficits
• Prevention Focus:
  • reinforces the importance of sustaining global maternal vaccination initiatives, expanding antenatal screening, and developing routine preventive strategies (e.g., vaccines against CMV)

Reference

• Sjöqvist H, Dalman C, Mataix-Cols D, et al. Congenital TORCH Infections and Neurodevelopmental Outcomes. JAMA Pediatr. Published online September 21, 2026. doi:10.1001/jamapediatrics.2026.4229