Mothers with iciHHV6 have an increased risk of spontaneous abortion

Investigators led by Tetsushi Yoshikawa of Fujita Health University School of Medicine in Japan studied 23 iciHHV6 cases that included mothers and 15 fathers positive for iciHHV6. They also studied cases that were negative for iciHHV6. Mothers carrying iciHHV6 fetuses of paternal origin were not more likely to have spontaneous abortion.

Intrigued by the fact that they found more iciHHV6 cases of paternal than maternal origin, the researchers studied the pregnancy history of families affected by iciHHV6. Eight mothers with iciHHV6 had 8 spontaneous abortions in 29 pregnancies, a far higher rate than in controls or in pregnancies with fetal iciHHV6 inherited from the father. Furthermore, 3 (37.5%) of the 8 iciHHV6 mothers had two or more spontaneous abortions compared to 6.3% of non iciHHV6 mothers.

A recent British study found that women with iciHHV6+ fetuses have a 2.5 to 3-fold increased risk of pre-eclampsia (Gaccioli 2020). HHV-6 RNA transcripts were found in 6.1% of cases of preeclampsia and only 2.2% of other pregnancies (p=0.008).

The authors suggest two possible mechanisms by which reactivated HHV-6 from an integrated viral genome could cause spontaneous abortion or preeclampsia: (1)direct cellular damage or (2) bystander effects (such as upregulation of inflammatory cytokines) induced by the viral reactivation

A few previous reports have tied HHV-6A infection to spontaneous abortion (Ando 1992, Revest 2011) and neonatal hypotonia (Drago 2008). Italian investigators have also tied HHV-6A infection to unexplained female infertility (Marci 2016) and demonstrate that HHV-6A infection of endometrial endothelial cells result in a disruption of the maternal immune system. (Bortolotti 2019). Endometrial cells infected with HHV6A are less receptive to trophoblast cells (Bortolotti 2020).

The authors hope that this finding will help physicians address a subset of recurrent spontaneous abortions which are unexplained in 50% of cases.

Read the full paper: Miura 2021