Background: Genital herpes simplex virus (GHSV) infection, especially asymptomatic GHSV infection, is likely an overlooked risk factor for preeclampsia (PE), which is largely a disease of the placenta with an underlying etiology related to placental inflammation and immune dysfunction. Once infected, the herpes virus remains in one’s body permanently. Women with GHSV infection, even without symptoms, continue to shed the virus during pregnancy, and are at higher risk of placental inflammation leading to pregnancy complications that include PE. Effective medications for treating GHSV infection exist. Therefore, treating women with GHSV infection during pregnancy could potentially lead to reductions in PE risk.
Objectives: To determine whether treating women with GHSV infection during pregnancy reduces the risk of PE.
Methods: A prospective cohort study was conducted among 89,131 pregnant Kaiser Permanente Northern California members. Four cohorts were established based on the combination of GHSV infection and treatment status: women with clinically diagnosed GHSV infection that was not treated during pregnancy (untreated); women with GHSV who received treatment (anti-herpes medications) for < 20 days (treated for short duration); women with GHSV who received treatment for ≥ 20 days (treated for longer duration); and women with neither GHSV infection nor any treatment (unexposed). Logistic regression was used to estimate the risk of PE associated with GHSV infection and its treatment including assessment of a dose-response relationship.
Results: After adjusting for potential confounders, women with untreated GHSV infection were at increased risk of PE compared to women without the infection (adjusted odds ratio [aOR], 1.37; 95% CI, 1.18-1.59). Overall, treating GHSV infection during pregnancy was associated with a 40% reduced risk of PE, compared with untreated infection (aOR, 0.60; 95% CI, 0.50-0.73). The treatment was most effective for medication use ≥20 days, with more than 50% reduction in PE (aOR, 0.49; 95% CI, 0.40-0.60) while shorter duration treatment ( < 20 days) was not associated with reduced risk of PE compared to untreated GHSV infection.
Conclusions: This study provides new evidence that pregnant women with GHSV infection, if untreated, are at higher risk of PE compared to those without GHSV infection. More importantly, treating such women with currently available anti-herpes medications during pregnancy is effective in reducing the risk of PE, especially when taking medications for a relatively longer duration (≥20 days). This new knowledge could provide the rationale for proactively identifying pregnant women with GHSV infection (e.g., through prenatal screening) and evidence for how to treat them to reduce PE.
.jpg "De-Kun Li, MD, PhD (he/him/his) photo")
