Autism Linked to Herpes Infection in Pregnancy

Megan Brooks

March 01, 2017

High levels of maternal antibodies against herpes simplex virus 2 (HSV-2) in mid-pregnancy has been linked to an increased risk for autism spectrum disorder (ASD), a new study suggests.

"This is the first study to report an association between maternal anti-HSV-2 antibody levels and risk of ASD in offspring," write the investigators, with first author Milada Mahic, PhD, a postdoctoral research scientist with the Center for Infection and Immunity, Columbia University Mailman School of Public Health in New York City.

"We believe the mother's immune response to HSV-2 could be disrupting fetal central nervous system development, raising risk for autism," Dr Mahic said in a statement.

The study was published online February 22 in mSphere, a journal of the American Society for Microbiology.

Sex-Specific Risk?

Maternal infections during pregnancy have been implicated in several neurodevelopmental disorders, including ASD.

The Columbia team assessed possible ties between maternal exposure to five pathogens (Toxoplasma gondii, rubella virus, cytomegalovirus, HSV-1, and HSV-2) during pregnancy and the risk for ASD in offspring. Exposure to these so-called "ToRCH" pathogens during pregnancy can lead to miscarriage and birth defects.

The investigators examined blood samples from 442 mothers of children diagnosed with ASD and 463 mothers of children without ASD who were enrolled in the Autism Birth Cohort (ABC) Study, which is run by the Norwegian Institute of Public Health. Maternal blood samples were obtained at around week 18 of pregnancy and at delivery.

High levels of HSV-2 IgG antibodies in maternal plasma at mid-pregnancy (but not at delivery) were associated with increased risk for ASD in male offspring.

After adjusting for parity and child's birth year, an increase in anti-HSV-2 levels from 240 to 640 arbitrary units/mL was associated with about a twofold higher likelihood of ASD in boys (odds ratio, 2.07; 95% confidence interval, 1.06 - 4.06; P = .03), the researchers report.

The number of girls with ASD (n = 78) in the study is "too small to conclude that the effect is sex specific; nonetheless, autism has a sex bias skewed toward males," they note in their article.

No association was found between ASD and the presence of IgG antibodies to the other four pathogens.

"The cause or causes of most cases of autism are unknown," senior author W. Ian Lipkin, MD, director of the Center for Infection and Immunity at Columbia University, said in the statement. "But evidence suggests a role for both genetic and environmental factors. Our work suggests that inflammation and immune activation may contribute to risk. Herpes simplex virus–2 could be one of any number of infectious agents involved."

The researchers note that the elevated HSV-2 antibody levels may indicate either recent primary infection or reactivation of latent infection. Only 12% of HSV-2-seropositive mothers reported having HSV lesions before pregnancy or during the first trimester, indicating that most HSV-2 infections were asymptomatic.

The researchers speculate that ASD risk associated with high levels of antibodies to HSV-2 is not specific to HSV-2 but instead reflects the impact of immune activation and inflammation on a vulnerable developing nervous system. They say further study is needed to determine whether screening and suppression of HSV-2 infection during pregnancy is needed.

The study was supported by grants from the National Institutes of Health, 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 Norway. The authors have disclosed no relevant financial relationships.

mSphere. Published online February 22, 2017. Full text

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