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Updated: Jun 23, 2025
Author Spotlight: Modeling an Aspect of Preeclampsia in Female Mice Using Hypoxic Human Placenta-Derived Small Extracellular Vesicles
Published on: January 26, 2024
Fetal cord plasma herpesviruses and preeclampsia: an observational cohort study
Inka Häkkinen1,2, Gamze Yazgeldi Gunaydin1,2, Lari Pyöriä3
1Stem Cells and Metabolism Research Program, University of Helsinki, Helsinki, Finland.
Insights
Human herpesviruses, including chromosomally integrated HHV-6 (ici-HHV-6), are not a significant cause of preeclampsia (PE). However, ici-HHV-6 may pose risks to fetal growth and development.
Area of Science:
- Virology
- Obstetrics
- Genetics
Background:
- Previous research suggested a link between chromosomally integrated human herpesvirus 6 (ici-HHV-6) and preeclampsia (PE).
- The prevalence and role of human herpesviruses in PE require further investigation.
Purpose of the Study:
- To investigate the association between human herpesviruses, particularly ici-HHV-6, and preeclampsia (PE).
- To determine the population prevalence of ici-HHV-6.
Main Methods:
- Multiplex quantitative PCR (qPCR) was used to detect DNA of nine human herpesviruses in cord plasma samples from 1276 pregnancies (539 PE, 737 controls) and 30 PE placentas.
- Whole-genome sequencing data from 3421 biobank subjects were analyzed to assess ici-HHV-6 population prevalence.
Main Results:
- Herpesviral DNA was detected in only 0.37% of PE samples and 0.14% of control samples.
- One PE sample had ici-HHV-6B, another had HHV-7. A control sample had ici-HHV-6B, associated with fetal growth restriction and preterm birth.
- No herpesviruses were found in PE placentas. Population prevalence of ici-HHV-6 was very low (0.08% for HHV-6B).
Conclusions:
- Human herpesviruses are unlikely to be a significant cause of preeclampsia (PE).
- Chromosomally integrated HHV-6 (ici-HHV-6) may present a risk for fetal growth restriction and preterm birth in pregnancies with maternal hypertension.
Abstract:
A previous study suggested that fetal inheritance of chromosomally integrated human herpesvirus 6 (ici-HHV6) is associated with the hypertensive pregnancy disorder preeclampsia (PE). We aimed to study this question utilizing cord plasma samples (n = 1276) of the Finnish Genetics of Preeclampsia Consortium (FINNPEC) cohort: 539 from a pregnancy with PE and 737 without. We studied these samples and 30 placentas from PE pregnancies by a multiplex qPCR for the DNAs of all nine human herpesviruses. To assess the population prevalence of iciHHV-6, we studied whole-genome sequencing data from blood-derived DNA of 3421 biobank subjects. Any herpes viral DNA was detected in only two (0.37%) PE and one (0.14%) control sample (OR 2.74, 95% CI 0.25-30.4). One PE sample contained iciHHV-6B and another HHV-7 DNA. The control's DNA was of iciHHV-6B; the fetus having growth restriction and preterm birth without PE diagnosis. Placentas showed no herpesviruses. In the biobank data, 3 of 3421 subjects (0.08%) had low level HHV-6B but no iciHHV-6. While iciHHV-6 proved extremely rare, both fetuses with iciHHV-6B were growth-restricted, preterm, and from a pregnancy with maternal hypertension. Our findings suggest that human herpesviruses are not a significant cause of PE, whereas iciHHV-6 may pose some fetal risk.
