Maternal Genital Herpes Infection Linked to Risk for Autism

Infants born to mothers with active genital herpes during early pregnancy are twice as likely to develop autism spectrum disorder (ASD) later in life, according to a study published inmSphere.

The study is the first to show evidence of the role of gestational infection in autism, indicating an association between maternal anti-herpes simplex virus-2 (HSV-2) antibodies and risk for ASD in offspring.

Because direct infection of the fetus is typically fatal, the investigators do not believe this is the cause of the risk. Instead, the findings suggest that neurodevelopment outcomes are due to primary or reactivation of infection in mothers with inflammation in close proximity to the womb.

“We believe the mother’s immune response to HSV-2 could be disrupting fetal central nervous system development, raising risk for autism,” said lead author Milada Mahic.

An estimated 1 of 5 women in the United States has HSV-2, also referred to as genital herpes. After the initial outbreak, the virus resides in nerve cells where it often lays dormant. The frequency of flare-ups starts to decrease as the body builds up an immunity to the virus.

The investigators sought to examine the link between maternal infection and the risk for autism, with a primary focus on the 5 pathogens toxoplasma gondii, rubella virus, cytomegalovirus, and herpes simplex virus types 1 and 2—–referred to collectively as ToRCH agents.

For the study, investigators examined blood samples obtained from 412 mothers of children diagnosed with ASD and 463 mothers of children without ASD enrolled in the Autism Birth Cohort (ABC) study.

Samples were taken at around week 18 of pregnancy and again at birth, and then were analyzed for levels of antibodies to each of the ToRCH agents.

The results of the study revealed high levels of antibodies to HSV-2 correlated with risk for ASD, the correlation was not observed with any of the other agents. Furthermore, the link was only evident in blood samples obtained at the time point reflecting exposure during early pregnancy, when the fetal nervous system undergoes rapid development, not at birth, according to the study.

The findings reflect those seen in earlier epidemiological data, which indicated that activation of the maternal immune system during early to mid-pregnancy was associated with long-term development and behavioral issues in offspring.

Overall, 13% of the mothers tested positive for anti-HSV-2 antibodies at mid-pregnancy. Of them, only 12% reported having HSV lesions before pregnancy or during the first trimester. This likely indicates that most infections wereasymptomatic, according to the authors.

The effect of anti-HSV-2 antibodies on the risk for ASD was only observed in males. The authors noted that because the number of females with ASD in the ABC study was small, there is not enough evidence to conclude that the effect is sex-specific. However, autism is generally more common in males.

More research needs to be done to determine if screening and suppression of HSV-2 infection during pregnancy is needed, the authors concluded.

“The cause or causes of most cases of autism are unknown,” said senior author Ian W. Lipkin. “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.”