Does Treating Genital Herpes Infection During Pregnancy Reduce the Risk of Preterm Delivery? A Prospective Cohort Study of 89,000 Pregnant Women

Background: Genital herpes infection (GHI), especially asymptomatic GHI, is likely an overlooked risk factor for preterm delivery (PTD). Women with GHI, even without symptoms, continue to shed the virus during pregnancy and have been shown to be at a higher risk of PTD. Effective medications for treating GHI exist. Treating women with GHI during pregnancy could potentially lead to reduction in PTD risk.

Objectives: To determine whether treating women with GHI during pregnancy reduces the risk of PTD.

Methods: A prospective cohort study was conducted in 89,132 pregnant Kaiser Permanente Northern California members. Four cohorts were established based on the combination of GHI and its treatment status: women with clinically diagnosed GHI that was not treated during pregnancy (untreated); women with GHI treated with medications before the 3rd trimester; women with GHI treated only during the 3rd trimester, and women with neither GHI nor any treatment. Cox proportional hazards regression was used to estimate the risk of PTD associated with GHI and its treatment, while accounting for different gestational ages at delivery, timing of initial treatment, and potential confounders. Sensitivity analysis using propensity score methodology was also conducted.

Results: Women with untreated GHI were at increased risk of PTD (almost 80% higher) compared to women without GHI (adjusted hazard ratio [aHR], 1.79; 95% CI, 1.57-2.04). Treating GHI during pregnancy was associated with a 27% reduced risk of PTD, compared with untreated GHI (aHR, 0.73; 95% CI, 0.60-0.88). The treatment was most effective for medication use ≥20 days, with an almost 50% reduction in PTD (aHR, 0.51; 95% CI, 0.40-0.66). The treatment appeared to be more effective if women started treatment before the 3rd trimester (aHR, 0.69; 95% CI, 0.54-0.87) than if they were only treated during the third trimester (aHR, 0.78; 95% CI, 0.60-1.01). Sensitivity analyses using PS methodology confirmed that the estimates for PTD were consistent and robust.

Conclusions: This study adds new evidence that women with GHI, if untreated, are at higher risk of PTD. More importantly, treating such women with currently available medications during pregnancy is effective in reducing the risk of PTD, especially when taking medications for over 20 days, and starting treatment before the 3rd trimester. This new knowledge could give rationale for prenatal screening for GHI and proactive treatment of GHI to reduce PTD.