Active Genital Herpes in Early Pregnancy Linked with Autism Spectrum Disorders

Mothers who experience active genital herpes infections during early pregnancy may be more likely to have offspring that will later be diagnosed with autism spectrum disorders (ASDs).

This is according to researchers at Columbia University’s Mailman School of Public Health and the Norwegian Institute of Public Health (NIPH) who revealed what may be the first immunological evidence that infections a mother experiences during pregnancy could affect autism outcomes in her unborn child. In the case of herpes infections, specifically the simplex virus-2 (HSV-2), “We believe the mother’s immune response to HSV-2 could be disrupting fetal central nervous system development,” said lead author Milada Mahic, PhD, a postdoctoral research scientist at the Mailman School in collaboration with NIPH.

Maternal infections have long been associated with abnormal fetal development, although the issue has become increasingly prevalent in the public eye as a result of Zika virus, which can lead to fetal microcephaly (unusually small head size), other brain abnormalities, and cardiovascular complications.

“Because the cause (or causes) of most cases of ASD is unknown…both genetic and environmental factors may be implicated,” Dr. Mahic explained. She added that these factors might include “gestational infection and immune activation.”

To determine whether or not high levels of herpes antibodies play a role in subsequent ASD diagnoses and whether fetal infection might be a factor, the group evaluated a cohort of 442 mothers of children with ASD and 464 mothers of children without ASD (the control group). Dr. Mahic noted that in other types of infections, such as Toxoplasma gondii, offspring of mothers who are infected can experience latent effects even if the infection occurred before conception.

“HSV-1, HSV-2, and cytomegalovirus frequently cause persistent or latent infections,” she said, adding that the team did not believe that direct HSV-2 infections of the fetus were to blame for the ASD diagnosis since these infections are often fatal prior to birth.

The group assembled a database of characteristics of mothers and offspring as well as collected 1781 plasma samples from the mothers. Upon evaluating these samples, the researchers found high levels of antibodies to HSV-2 in 13% of the mothers in the study at the 18-month testing point. Only 12% of that subpopulation reported having herpes lesions before getting pregnant or during the first trimester, leading the researchers to conclude that most of the infections were asymptomatic even when active. The researchers also noted that mothers of children with ASD “were younger, less likely to have college- or university-level education, and more likely to be first-time mothers.” They also said that children with ASD were “more likely to be born to first-time mothers.”

The group determined that the odds ratio of increased risk of ASD in male offspring if the mother had an active HSV-2 infection during early pregnancy was 2.07. The study did not find the same association between the infection and ASD diagnosis in female offspring, but noted that the female cohort was relatively small and, therefore, there was “not enough evidence to conclude that the effect is sex-specific.”

“This is the first study to report an association between maternal anti-HSV-2 antibody levels and risk of ASD in offspring,” Dr. Mahic said.

In March 2014, the Centers for Disease Control and Prevention (CDC) reported that one in every 68 babies born in the United States eventually received some form of ASD diagnosis. About one in every 54 boys are diagnosed on the spectrum. By comparison, in 2007, the CDC reported that about 1 in 150 children had ASD.

According to the CDC, 15.7% of individuals ages 14 to 49 had an HSV-2 infection as of 2014. At the same time, the CDC estimated that more than one in every five (20.3%) women had an HSV-2 infection. The overall population with HSV-2 infections declined from 21.0% in 1994 to 15.7% in 2010 and has held steady around that number from that point forward. Currently, if herpes symptoms are present at time of delivery, many doctors recommend cesarean delivery to prevent transmission to the infant, but a standard procedure does not exist for dealing with viral suppression during pregnancy.