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CME / CE

Autism and Herpes Infection in Pregnancy: Possible Link?

  • Authors: News Author: Megan Brooks; CME Author: Charles P. Vega, MD
  • CME / CE Released: 4/20/2017
  • THIS ACTIVITY HAS EXPIRED
  • Valid for credit through: 4/20/2018
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Target Audience and Goal Statement

This article is intended for primary care clinicians, obstetrician-gynecologists, nurses, and other clinicians who care for pregnant women and young children.

The goal of this activity is to provide medical news to primary care clinicians and other healthcare professionals in order to enhance patient care.

Upon completion of this activity, participants will be able to:

  • Assess whether viral antibody titers affect the risk for autism spectrum disorder (ASD) among children
  • Evaluate whether maternal herpes simplex virus titers during pregnancy may correlate with the risk for ASD among children

 


Disclosures

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Medscape, LLC, encourages Authors to identify investigational products or off-label uses of products regulated by the US Food and Drug Administration, at first mention and where appropriate in the content.


Author(s)

  • Megan Brooks

    Freelance writer, Medscape

    Disclosures

    Disclosure: Megan Brooks has disclosed no relevant financial relationships.

Editor(s)

  • Robert Morris, PharmD

    Associate CME Clinical Director, Medscape, LLC

    Disclosures

    Disclosure: Robert Morris, PharmD, has disclosed no relevant financial relationships.

CME Reviewer/Nurse Planner

  • Amy Bernard, MS, BSN, RN-BC

    Lead Nurse Planner, Medscape, LLC

    Disclosures

    Disclosure: Amy Bernard, MS, BSN, RN-BC, has disclosed no relevant financial relationships.

CME Author(s)

  • Charles P. Vega, MD

    Health Sciences Clinical Professor, UC Irvine Department of Family Medicine; Associate Dean for Diversity and Inclusion, UC Irvine School of Medicine, Irvine, California

    Disclosures

    Disclosure: Charles P. Vega, MD, has disclosed the following relevant financial relationships:
    Served as an advisor or consultant for: McNeil Consumer Healthcare
    Served as a speaker or a member of a speakers bureau for: Shire Pharmaceuticals


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CME / CE

Autism and Herpes Infection in Pregnancy: Possible Link?

Authors: News Author: Megan Brooks; CME Author: Charles P. Vega, MDFaculty and Disclosures
THIS ACTIVITY HAS EXPIRED

CME / CE Released: 4/20/2017

Valid for credit through: 4/20/2018

processing....

Clinical Context

The prevalence of autism spectrum disorder (ASD) is approximately 1% to 2% in higher income Western countries, yet the precise pathogenesis of ASD remains unknown. Environmental factors can play a role in the development of ASD, and Gentile and colleagues evaluated whether infection with a number of different viral agents might contribute to ASD. Their research compared 54 children with ASD vs 46 control children without ASD, published in the July-August 2014 issue of In Vivo. [1][2]

Researchers focused on antibody levels against herpes simplex virus (HSV) 1 and 2, cytomegalovirus, and Epstein-Barr virus among children with ASD and control children. Overall, they found that the rates of seropositive status were similar in the 2 groups of children. Moreover, mean antibody titer levels were similar in comparing children with vs those without ASD.

The authors of the current study were also interested in the potential role of viral infection in promoting ASD, but they focus on maternal immunoreactivity to HSV-2 and the rate of ASD among offspring.

Study Synopsis and Perspective

High levels of maternal antibodies against HSV-2 in midpregnancy have been linked with an increased risk for 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.[3]

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 5 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 Study, which is run by the Norwegian Institute of Public Health. Maternal blood samples were obtained at approximately week 18 of pregnancy and at delivery.

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

After adjustment for parity and child's birth year, an increase in anti-HSV-2 levels from 240 to 640 AU/mL was associated with an approximately 2-fold higher likelihood of ASD in boys (odds ratio [OR], 2.07; 95% confidence interval [CI], 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 4 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 are 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.

Study Highlights

  • The current study used data from the Norwegian Mother and Child Cohort Study, which includes information on more than 110,000 children born in Norway between 1999 and 2008.
  • Children with ASD were identified through screening questionnaires completed at ages 3, 5, and 7 years. Diagnosis codes in national registers identified other children with ASD.
  • Women enrolled in the study had serum IgG antibody levels against T gondii, rubella virus, cytomegalovirus, HSV-1, and HSV-2 (ToRCH infections) drawn at approximately 18 weeks' gestation, and again immediately after delivery.
  • The main outcome of the current study was the potential relationship between maternal antibody titers to ToRCH infections and the risk for ASD among children.
  • Serum samples from 442 mothers of children with ASD were compared vs those of 464 mothers of children in the control group. Compared with mothers in the control group, mothers of children with ASD were more likely to be tested during their first pregnancy.
  • 80% of children included in the study sample were boys.
  • Overall, there was no significant difference in maternal antibody titers against any particular pathogen in comparing the ASD group vs the control group. This remained true in separate analyses for girls and boys.
  • Researchers evaluated the rate of seroconversion from negative to positive from the midpregnancy to postpartum time points. This rate was low overall, but it suggested a possible association between high levels of antibodies to HSV-2 and the risk for ASD among boys.
  • Secondary analyses showed that the risk for ASD began to increase among boys when the midpregnancy HSV-2 titer passed 400 AU/mL. When this level reached 640 AU/mL, which is a high level consistent with active infection, the OR of ASD was 2.07 (95% CI, 1.06-4.06) among boys, compared with a low seropositive level of 240 AU/mL.
  • No such relationship was noted between higher HSV-2 antibody titers at the time of delivery and the risk for ASD among boys, nor was there any association between HSV-2 titers and the risk for ASD among girls. The low number of girls in the study may have resulted in a lack of statistical power in this outcome.
  • The authors note that the inflammation associated with infection, not the HSV-2 infection itself, may be the factor that promotes ASD among boys.

Clinical Implications

  • Previous studies failed to find a difference in seropositive status or antibody titer levels for HSV-1, HSV-2, cytomegalovirus, and Epstein-Barr virus in comparing children with vs those without ASD.
  • The current study by Mahic and colleagues examined whether maternal antibodies to ToRCH infections might predict the risk for ASD among offspring. Overall, the study findings are negative, although secondary analyses demonstrated that high maternal titers to HSV-2 during midpregnancy were associated with an increased risk for ASD.
  • Implications for the Healthcare Team: The results of the current study should not cause a panic in the millions of adults infected with HSV-2. The healthcare team should counsel pregnant women about the known dangers of active HSV-2 infection during pregnancy and, particularly, take steps to prevent the vertical transmission of infection at the time of delivery.

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