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Induction of Maternal Immune Activation in Mice at Mid-gestation Stage with Viral Mimic Poly(I:C)
Published on: March 25, 2016
Childhood epilepsy and maternal antibodies to microbial and tissue antigens during pregnancy
Yuelian Sun1, Jakob Christensen, Jørn Olsen
1Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus 8000C, Denmark.
Introduction:
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.
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