Maternal Rubella Susceptibility and Autism in Offspring: Case-Control Study of Maternal Non-Immunity and Low Immunity

Jill Hutton, Paul J. Rowan, Anthony Greisinger and Melanie Mouzoon

Objective: Autism may arise from any of several categories of harm, including genetic, environmental, perinatal, and drug exposures. Rubella has been examined as one of the viral causes of autism. We designed a study to determine whether antenatal susceptibility to rubella, shown by low or no immunity when tested in the antepartum, was associated with child autism spectrum disorders. Study Design: Children ages 2.5 years to 7.5 years with autism spectrum disorder were identified, and matched on age and sex with children having no such diagnosis. To identify mothers who were rubella-susceptible, we noted those with pregnancy rubella IgG values under 10 IU/mL; since low-immunity might also pose a risk, we analyzed those with IgG values under 20 IU/mL. Exclusion criteria included preterm delivery, child brain injury or genetic disorder, and maternal use of anti-epileptic or illicit drugs. Results: For the years 2007 to 2011, we identified 56 children with autism meeting study criteria, and identified suitable children as matched controls. Of the 56 autism-case mothers, one had a rubella IgG value under 10 IU/mL, while 6 of the control mothers had an IgG value under 10 IU/mL. For the low-immunity group, 19 of the autism-case mothers had an IgG value under 20 IU/mL, while 18 of the control mothers had an IgG value under 20 IU/mL. These associations were tested with McNemar’s exact (binomial) test. There was no statistical relationship between the presence of an autism diagnosis and mother’s rubella susceptibility at the <10 IU/mL level (p=0.13), and at the <20 IU/mL level (p=0.85). Conclusions: We failed to find evidence supporting the concept that antenatal rubella susceptibility was associated with child autism. Results are not conclusive since this exploratory study was under-powered. We believe that the hypothesis warrants more investigation, including studies with greater power and complementary approaches.