Women who were actively infected with genital herpes during early pregnancy were twice as likely to have a child who later developed autism, according to a study by scientists at the Center for Infection and Immunity at Columbia University's Mailman School of Public Health Spectrum Disorder (ASD) was diagnosed and the Norwegian Public Health Institute.
The study is the first to provide immunological evidence of the role of pregnancy infection in autism and to report an association between maternal anti-herpes simplex virus-2 (HSV-2) antibodies and the risk of ASA in offspring. Results appear in mSphere , a journal of the American Society for Microbiology.
We believe the mother's immune response to HSV-2 could disrupt fetal central nervous system development and increase the risk of autism, says lead author Milada Mahic, a postdoctoral fellow at the Center for Infection and Immunity and the Norwegian Institute for Public Health Public.
The authors do not believe that the risk is due to direct infection of the fetus, as such infections are typically fatal. Instead, they suggest that the neurodevelopmental results are due to primary or reactivated infection in mothers with inflammation in close proximity to the uterus.
About one in five American women carries HSV-2, also known as genital herpes, a highly contagious and lifelong infection that usually spreads through sex. After an initial outbreak, the HSV-2 virus lives in nerve cells and is often inactive, with relapses of decreasing frequency as the body builds immunity to the virus.
Researchers tried to study the link between maternal infection and the risk of autism, focusing on five pathogens collectively known as ToRCH: Toxoplasma gondii , Rubella virus, cytomegalovirus, and herpes simplex viruses types 1 and 2, which can cause miscarriages and birth defects during pregnancy. They examined blood samples from 412 mothers of children diagnosed with ASD and 463 mothers of children without ASD who participated in the Autism Birth Cohort (ABC) Study, monitored by the Norwegian Public Health Institute. Samples were taken at two points in time - around the 18th week of pregnancy and at birth - and analyzed for antibody levels against each of the ToRCH active ingredients.
They found high levels of antibodies against HSV-2, not against any of the other drugs that correlated with ASA risk. This association was only seen in blood samples taken at a time point reflecting exposure during early pregnancy, when the fetal nervous system is undergoing rapid development, not at birth. The finding reflects earlier epidemiological data suggesting that activation of the maternal immune system during early to mid-pregnancy is associated with long-term development and behavior problems in the offspring.
Overall, 13 percent of the mothers in the study tested positive for anti-HSV-2 antibodies in mid-pregnancy. Of these, only 12 percent said they had HSV lesions before pregnancy or during the first trimester, a likely indication that most infections were asymptomatic.
The effect of anti-HSV-2 antibodies on ASA risk was only observed in men, not women. However, because the number of women with ASA is small in the ABC study, the researchers say there isn't enough evidence to conclude that the effects are gender-specific, although autism is generally more common in men.
According to the authors, more studies are needed to determine whether screening and suppression of HSV-2 infection is needed during pregnancy.
The cause or causes of most cases of autism are unknown, says senior author W. Ian Lipkin, director of the Center for Infection and Immunity and John Snow Professor of Epidemiology at the Mailman School of Columbia. However, there is evidence that both genetic and environmental factors play a role. Our work suggests that inflammation and immune activation may contribute to the risk. Herpes simplex virus 2 could be one of several infectious agents involved.
Co-authors are Siri Mjaaland from the Center for Infection and Immunity and the Norwegian Institute for Public Health; Mady Hornig, Ezra Susser, Michaeline Bresnahan, Bruce Levin, and Xiaoyu Che at the Mailman School of Columbia; and Hege Marie Bøvelstad, Nina Gunnes, Anne-Siri Øyen, Ted Reichborn-Kjennerud, Synnve Scholberg, Per Magnus, Christine Roth, Camilla Stoltenberg and Pål Surén from the Norwegian Institute for Public Health; and Deborah Hirtz from U.S. National Institute of Neurological Disorders and Stroke.
The study was supported by grants from the National Institutes of Health (NS47537, NS086122), the Jane Botsford Johnson Foundation, the Simons Foundation Autism Research Initiative, the Norwegian Ministry of Health and Care Services, the Norwegian Ministry of Education and Research, and the Research Council of . supports Norway. The authors do not report any conflicts of interest.