Autism Risk Linked to Maternal Genital Herpes During Early Pregnancy

Summary: A study finds an association between maternal genital herpes infection during early pregnancy and an increased risk of autism spectrum disorder (ASD) in children, particularly males.

Source: Columbia University

Researchers at Columbia University’s Mailman School of Public Health and the Norwegian Institute of Public Health report that women with evidence of active genital herpes (HSV-2) during early pregnancy had about twice the odds of giving birth to a child later diagnosed with autism spectrum disorder. The study provides immunological evidence linking maternal infection and immune response during gestation with ASD risk in offspring.

The research, published in the journal mSphere, measured levels of antibodies to several prenatal infectious agents in blood samples collected from mothers enrolled in the Autism Birth Cohort (ABC) Study. The investigators focused on ToRCH agents—Toxoplasma gondii, rubella virus, cytomegalovirus (CMV), herpes simplex virus type 1 (HSV-1), and herpes simplex virus type 2 (HSV-2)—because exposure to these pathogens during pregnancy is known to affect fetal development.

Using plasma samples taken at about week 18 of pregnancy (midpregnancy) and at delivery, the team compared antibody levels from 412 mothers of children later diagnosed with ASD to 463 mothers of children without ASD. High levels of maternal antibodies to HSV-2 at midpregnancy, but not at delivery, were associated with increased risk of ASD in offspring. This timing corresponds to an important window of neural development when the fetal central nervous system is rapidly forming, supporting the idea that maternal immune activation during early-to-mid pregnancy may influence long-term neurodevelopment.

About 13 percent of the mothers in the study tested positive for anti-HSV-2 antibodies at midpregnancy. Most of these infections appeared to be asymptomatic: only around 12 percent of those women reported visible HSV lesions before pregnancy or during the first trimester. The authors emphasize that the observed association is unlikely to reflect direct fetal infection—such events are generally rare and can be severe—rather it may reflect maternal immune activation or localized inflammation near the womb during episodes of primary infection or viral reactivation.

The association between elevated anti-HSV-2 antibody levels and ASD risk was primarily detected in male offspring. The research team cautions that the number of female ASD cases in the cohort was relatively small, so further work is needed to determine whether the effect truly differs by sex or reflects sample size limitations. Autism is already known to be more commonly diagnosed in males, but clarifying sex-specific mechanisms remains a key research priority.

These findings do not establish causation, but they add to growing evidence that maternal infection and immune responses during pregnancy can contribute to neurodevelopmental outcomes. According to the senior author, W. Ian Lipkin, genetic and environmental factors likely act together in most ASD cases, and gestational inflammation or immune activation may be among the environmental contributors. HSV-2 infection could be one of multiple infectious triggers worth investigating.

The study team included researchers from the Center for Infection and Immunity at Columbia University’s Mailman School of Public Health and the Norwegian Institute of Public Health. Co-authors listed by the study include scientists from both institutions and collaborators from the U.S. National Institute of Neurological Disorders and Stroke.

Funding and disclosures: The research 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 reported no conflicts of interest.

• High maternal antibody levels to herpes simplex virus type 2 (HSV-2) at midpregnancy were associated with an increased risk of autism spectrum disorder in offspring, particularly males.
• The association was specific to HSV-2 among the ToRCH agents tested and was observed only in samples reflecting early pregnancy exposure—not in samples collected at delivery.
• Most HSV-2 infections in the study were asymptomatic, suggesting that cryptic or reactivated infections may still produce immune responses relevant to fetal neurodevelopment.
• Further research is needed to replicate these results, clarify any sex-specific effects, and explore whether screening or antiviral suppression during pregnancy could reduce potential risk.

Abstract summary: Maternal infections during pregnancy have been linked to neurodevelopmental disorders. In the ABC cohort, high maternal midpregnancy HSV-2 IgG antibody levels were associated with elevated ASD risk in male offspring after adjusting for parity and birth year. No associations were found for antibodies to Toxoplasma gondii, rubella, CMV, or HSV-1. The results support the hypothesis that gestational immune activation may influence autism risk and encourage further study of maternal infection monitoring and preventive strategies.

Study: “Maternal Immunoreactivity to Herpes Simplex Virus 2 and Risk of Autism Spectrum Disorder in Male Offspring.” Published in mSphere, February 2017. Authors include Milada Mahic, Siri Mjaaland, Hege Marie Bøvelstad, Nina Gunnes, Ezra Susser, Michaeline Bresnahan, Anne-Siri Øyen, Bruce Levin, Xiaoyu Che, Deborah Hirtz, Ted Reichborn-Kjennerud, Synnve Schjølberg, Christine Roth, Per Magnus, Camilla Stoltenberg, Pål Surén, Mady Hornig, and W. Ian Lipkin.