Childhood epilepsy and maternal antibodies to microbial and tissue antigens during pregnancy.
BACKGROUND
Several epidemiologic studies show associations between mother's infections during pregnancy and an increased risk of mental and neurological disorders in the offspring. Such associations could be due to the direct or indirect effects of infectious agents, including immune responses to infectious agents that display molecular mimicry with host antigens. We measured a range of antigen-specific maternal IgG antibodies to examine if any were associated with risk for childhood epilepsy in offspring.


METHODS
We used a case-cohort design within the Danish National Birth Cohort (DNBC) to examine maternal IgG antibodies to 25 microbial and tissue antigens during pregnancy and their association with the risk of epilepsy in offspring. The source population of this study was 68,250 live born singletons with up to 10 years of follow up. We randomly identified a sample of 282 children as a subcohort and included 275 children with a verified diagnosis of epilepsy as cases. Maternal antibodies were categorized into 6 groups (<50, 50-59, 60-69, 70-79, 80-89, ≥90 percentile) according to the level in the subcohort. We used a Prentice-weighted Cox regression model to estimate the hazard ratio (HR) and 95% confidence interval (CI) for epilepsy according to measured antibodies.


RESULTS
Higher levels of maternal antibodies against herpes simples virus type 1 (anti-HSV1) were associated with a slightly higher risk of childhood epilepsy (HR for trend=1.09, 95% CI: 0.99-1.21), while higher levels of maternal antibodies against pneumococcal polysaccharide 18 (anti-PnPS18) were associated with a lower risk of childhood epilepsy (HR for trend=0.90, 95% CI: 0.81-1.01). Among the subtypes, a significantly higher risk associated with anti-HSV1 antibodies was seen for childhood absence epilepsy (HR for trend=2.08, 95% CI: 1.12-3.85) and for epileptic encephalopathies (HR for trend=1.49, 95% CI: 1.01-2.22). The significantly lower risk associated with anti-PnPS18 antibodies was observed for infantile spasms (HR for trend=0.47, 95% CI: 0.27-0.83).


CONCLUSIONS
Maternal anti-HSV1and anti-PnPS18 antibodies during pregnancy may be associated with the risk of epilepsy in offspring, but any potential etiologic and preventative implications of these associations warrant further exploration.
Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus 8000C, Denmark. Electronic address: ys@soci.au.dk.
Yuelian
Y
Sun
Jakob
J
Christensen
Jørn
J
Olsen
D000328:Adult; D000906:Antibodies / Q000276:immunology*; D002648:Child; D004827:Epilepsy / Q000209:etiology* / Q000276:immunology; D005260:Female; D018259:Herpesvirus 1, Human / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000209:etiology* / Q000276:immunology
D000906:Antibodies; D007074:Immunoglobulin G
Antibodies; BMI; CI; DNBC; Danish National Birth Cohort; Epilepsy; HR; HSV1; ICD; Infection; International Classification of Diseases; Microbial antigen; Molecular mimicry; PnPS18; Tissue antigen; body mass index; confidence interval; hazard ratio; pneumococcal polysaccharide 18; simples virus type 1