What was the research about?
Genital herpes is a sexually transmitted infection. In pregnant women, genital herpes can cause problems for the baby. For example, genital herpes may increase the risk of having a baby before 37 weeks, called preterm birth, or of having a baby with low birthweight.
In this study, the research team wanted to learn if
- Treating genital herpes in pregnant women lowered the risk of preterm birth and low birthweight
- The timing or length of treatment lowered the risk of preterm birth and low birthweight
What were the results?
Preterm birth. Among pregnant women with genital herpes,
- Women who received treatment had a lower risk of preterm birth than women who didn’t receive treatment.
- Women who received treatment before the third trimester had a lower risk of preterm birth than women who received treatment in the third trimester.
- Women whose treatment lasted 20 days or more had a lower risk of preterm birth than women who didn’t receive treatment. But women who received treatment for less than 20 days didn’t have a lower risk of preterm birth than women who didn’t receive treatment.
The risk of preterm birth didn’t differ between women with genital herpes who received treatment and women who didn’t have genital herpes.
Low birthweight. Compared with women who didn’t receive treatment, among those who did, treatment, treatment timing, and length of treatment did not reduce the risk of low birthweight.
Who was in the study?
The study included data from 89,132 women in northern California who were at least 20 weeks pregnant during the study. Of these, 35 percent were White, 26 percent were Asian, 6 percent were African American, and 6 percent were other races; 26 percent were Hispanic. In this study, 14 percent of women had genital herpes, used herpes medicine, or both.
What did the research team do?
The research team reviewed health records of pregnant women to see if treatment, treatment timing, or length of treatment reduced the risk of preterm birth and low birthweight.
Women who had genital herpes during pregnancy, doctors, and patient health organizations helped plan and conduct the study.
What were the limits of the study?
Because the research team didn’t assign women by chance to receive treatment, the team can’t say for sure if the changes in preterm delivery happened because of the treatment. Differences could be due to patient characteristics, such as other existing health problems.
Future research could use a clinical trial to learn more about how treating genital herpes during pregnancy affects birth outcomes.
How can people use the results?
Women and their doctors can use the results when considering whether and how to treat genital herpes during pregnancy.
To determine the effectiveness of herpes treatment on reducing the risk of preterm delivery and low birthweight in pregnant women
|Design||Observational: cohort study|
|Population||89,132 pregnant women in northern California who were at least 18 years old|
Effectiveness of treatment timing:
Effectiveness of treatment duration:
|Outcomes||Preterm delivery (birth before 37 weeks gestation); low birthweight (babies born weighing under 5 pounds 8 ounces)|
This prospective observational cohort study examined whether treating genital herpes in pregnant women reduced the risk of preterm delivery and low birthweight compared with no treatment. Researchers also compared the effectiveness of treatment timing and duration on improving birth outcomes.
Researchers collected information on clinical diagnosis and treatment using electronic health records and pharmacy databases from a large clinical registry in northern California.
The study included 89,132 women who were at least 20 weeks pregnant. Of these, 35% were White, 26% were Asian, 6% were African American, and 6% were other races. In addition, 26% were Hispanic. The average age was 31. In this study, 14% of women had indications of genital herpes infection, used herpes medicine, or both.
Women who had genital herpes during pregnancy, doctors, and patient health organizations provided input on the study.
Preterm delivery. Among women who had genital herpes,
- Treatment during pregnancy resulted in a 27% lower risk of preterm delivery compared with no treatment (adjusted hazard ratio [aHR]=0.73; 95% confidence interval [CI]: 0.60, 0.88).
- Compared with women who did not receive treatment, women who received treatment before the third trimester had a 31% lower risk of preterm delivery (aHR=0.69; 95% CI: 0.54, 0.87) while women who received treatment during the third trimester had a 22% lower risk (aHR=0.78; 95% CI: 0.60, 1.01).
- Compared with women who did not receive treatment, women who received treatment for 20 days or more had a 49% lower risk of preterm delivery (aHR=0.51; 95% CI: 0.40, 0.66). Women who received treatment for less than 20 days did not differ significantly from those who did not receive treatment.
The risk of preterm delivery did not differ significantly between women who received treatment for genital herpes during pregnancy and women who did not have genital herpes.
Low birthweight. Compared with no treatment, receiving treatment, treatment timing, and treatment duration did not reduce the risk of low birthweight.
Because researchers did not randomly assign women to receive treatment, differences seen across outcomes may be because of differences in the patient populations.
Conclusions and Relevance
In this study, compared with no treatment, treatment for genital herpes during pregnancy reduced the risk of preterm delivery but not low birthweight. Among women with genital herpes, treatment before the third trimester and treatment that lasted 20 days or more reduced the risk of preterm delivery.
Future Research Needs
Future research could use a clinical trial to further examine how genital herpes treatment during pregnancy affects birth outcomes.
Final Research Report
View this project's final research report.
Peer review of PCORI-funded research helps make sure the report presents complete, balanced, and useful information about the research. It also assesses how the project addressed PCORI’s Methodology Standards. During peer review, experts read a draft report of the research and provide comments about the report. These experts may include a scientist focused on the research topic, a specialist in research methods, a patient or caregiver, and a healthcare professional. These reviewers cannot have conflicts of interest with the study.
The peer reviewers point out where the draft report may need revision. For example, they may suggest ways to improve descriptions of the conduct of the study or to clarify the connection between results and conclusions. Sometimes, awardees revise their draft reports twice or more to address all of the reviewers’ comments.
Peer reviewers commented and the researchers made changes or provided responses. Those comments and responses included the following:
- The reviewers asked how relevant the data were for pregnant women with latent herpes infection, not currently exhibiting symptoms. The researchers stated that the herpes virus is a continuous infection even when patients are asymptomatic, and that asymptomatic infection may still present a risk for fetal health. In the dataset it was not possible to distinguish women with symptoms from those without symptoms, so the researchers included both in the study cohorts and distinctions were not made in the results between the two groups.
- The reviewers asked for an explanation for why the study found treatment to be associated with reduced risk of preterm delivery (PTD) but did not find an association with low birthweight (LBW), even though the two often go together. The researchers said PTD may lead to LBW, but many other causes lead to LBW as well. They said they did not know why herpes treatment did not seem to affect LBW in this study, but this was not an unexpected finding since previous studies have seen different impacts of interventions on PTD versus LBW.
- The reviewers asked for clarification on the possible side effects of antiherpes drugs in pregnant women and asked why the researchers did not also look at material health outcomes, along with infant outcomes. The researchers responded that antiherpes medications consistently have been found to be quite safe and have been classified by the United States Food and Drug Administration in the same category of safety as prenatal vitamins. Moreover, the focus of this study was on preterm birth and low birthweight in infants, so the researchers were not looking at other outcomes such as maternal health or infant birth defects.
- The reviewers asked whether women with herpes who received antiviral medications were at the same risk of preterm delivery as women without infection and why maternal outcomes and the effects of race, age, and weight were not considered. The researchers replied that they observed only a very small difference in preterm delivery rates among women who received medications compared with women without infection, but the primary aim of the study was to compare treated and untreated women with herpes, not to compare them with women without infection, so that finding was not part of the PCORI study.
- The reviewers asked how underdiagnosis of herpes may have affected the study, for example in affecting the study’s power to detect an association between medication use and LBW. The researchers said that while herpes infection may have gone unrecognized in some women, herpes infection rates have gone down substantially in the United States in recent decades, so the researchers did not expect that a very large proportion of women in the comparator group had undetected herpes. In addition, the researchers emphasized that such misclassification would only have reduced the strength of any observed associations, not suggested associations that do not exist.
Conflict of Interest Disclosures
Patient / Caregiver Partners
No information provided by awardee
Other Stakeholder Partners
William Smith, National Coalition of STD Directors Deborah Arindell, American Sexual Health Association Dr. Tracy Flanagan, Kaiser Permanente Northern California Dr. Piero Garzaro, Kaiser Permanente Northern California
Study Registration Information
- Has Results