Does Treating Genital Herpes during Pregnancy Improve Birth Outcomes? [Internet]

Excerpt

Background: Clinicians and patients alike are likely to have overlooked the risks of genital herpes infection, especially asymptomatic genital herpes infection, among pregnant women in relation to preterm delivery (PTD) and low birth weight (LBW). Emerging literature shows that (1) women with asymptomatic (latent) genital herpes infection continue to shed the virus during pregnancy; (2) women with the infection have a higher risk of PTD than those without the infection; and (3) treating patients with existing antiherpes medications is effective in reducing the risk of PTD associated with genital herpes infection.

Objectives: This study was designed to address the following questions:

1. Aim 1: Does treating genital herpes infection in pregnant women reduce the risk of PTD or LBW?

2. Aim 2: Does the timing of the treatment during pregnancy influence the treatment effectiveness?

3. Aim 3: Do other treatment metrics, including treatment duration, influence treatment effectiveness?

4. Aim 4: Does treatment effectiveness vary depending on the subtype of underlying genital herpes infection?

5. Aim 5: Does genital herpes infection, if untreated in pregnancy, increase the risk of PTD and LBW compared with no genital herpes infection?

Methods: From March 2017 through September 2019, we conducted a member-population-based prospective cohort study among pregnant members of Kaiser Permanente Northern California who gave birth. For the 89 132 pregnant women in the final analyses, we established 4 cohorts on the basis of the combination of genital herpes infection and treatment with antiherpes medications, including acyclovir and valacyclovir, during pregnancy. Our 2 primary outcomes were PTD and LBW. We used Cox proportional hazard regression to estimate the associations, while adjusting for different gestational ages (in days) at delivery and at the time of treatment initiation and controlling for potential confounders, including a history of sexually transmitted infections other than genital herpes and sociodemographic characteristics. To examine further the consistency and robustness of the estimates, we also conducted sensitivity analyses using propensity score (PS) methodology and adjusting for additional risk factors collected by interviewing a subcohort of the study population.

Results: Women with a clinical diagnosis of genital herpes infection were at increased risk of PTD (almost 80% higher) than women without the infection (adjusted hazard ratio [aHR], 1.79; 95% CI, 1.57-2.04). Use of antiherpes medications was associated with a 27% reduced risk of PTD among women with genital herpes infection during pregnancy compared with the risk among women with untreated infection during pregnancy (aHR, 0.73; 95% CI, 0.60-0.88). The treatment effect was attributable largely to longer use of antiherpes medications (≥20 days), with an almost 50% reduction in PTD compared with untreated women (aHR, 0.51; 95% CI, 0.40-0.66). The treatment appeared to be more effective if women were treated early in pregnancy (before the third 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) and if genital herpes infections were diagnosed in early pregnancy (aHR, 0.33; 95% CI, 0.23-0.47) than if they were not diagnosed in early pregnancy (aHR, 0.69; 95% CI, 0.45-1.04). We conducted sensitivity analyses using PS methodology and adjusted for additional factors obtained from the interviews with the subcohort randomly selected from the overall cohorts; these analyses showed that the estimates for PTD were consistent and robust. Although genital herpes infection was associated with increased risk of LBW (aHR, 1.65; 95% CI, 1.41-1.95), treating women with this infection during pregnancy did not appear to change the LBW risk associated with the infection.

Conclusions: This study provides more evidence that women with genital herpes infection, if untreated during pregnancy, are at increased risk of PTD. More importantly, treating such patients with currently available antiherpes medications during pregnancy was effective in mitigating the risk of PTD associated with genital herpes infection. Our results reveal new findings that treatment effectiveness requires taking the medications for at least 20 days, and the effect is more pronounced when initiated earlier in pregnancy (before the third trimester) and among those who were symptomatic in early pregnancy. In contrast, treating genital herpes infection during pregnancy does not seem to mitigate the risk of LBW associated with the infection. If future studies confirm our findings, genital herpes infection is likely an important, yet overlooked, risk factor for PTD for which effective treatment medications exist. This new knowledge could potentially change prenatal screening for genital herpes infection and encourage proactive treatment to reduce PTD for those with the infection.

Limitations: Like any observational study, uncontrolled and unmeasured confounders should always be kept in mind as possible alternative explanations. None of the findings presented should be considered as causal by themselves. We did not have information to determine the reason why women with a clinical diagnosis of genital herpes infection in early pregnancy had a higher risk of PTD (aHR, 3.55; 95% CI, 2.85-4.43) than those with a diagnosis later in pregnancy or only before pregnancy (aHR, 1.44; 95% CI, 1.23-1.68). Future studies could shed more light on this issue.