Obstetrics & Gynecology:
Prenatal Herpes Simplex Virus Serologic Screening Beliefs and Practices Among Obstetricians
Gardella, Carolyn MD, MPH1; Barnes, Julia MD1; Magaret, Amalia S. PhD2; Richards, Julie2; Drolette, Linda2; Wald, Anna MD, MPH2,3,4
From the Departments of 1Obstetrics & Gynecology, 2Laboratory Medicine, 3Medicine, and 4Epidemiology, University of Washington, Seattle, Washington.
Supported by National Institutes of Health (NIH) grant AI-30731. Dr. Wald also is supported by NIH K24 AI071113.
Presented in part at the Annual Clinical Meeting of the American College of Obstetricians and Gynecologists, San Diego, California, May 5–9, 2007.
Corresponding author: Carolyn Gardella, MD, MPH, Assistant Professor, Department of Obstetrics & Gynecology, University of Washington, Box 356460, Seattle, WA 98119; e-mail: firstname.lastname@example.org.
Financial Disclosure Dr. Wald received grant support from GlaxoSmithKline (Research Triangle Park, NC), Antigenics (New York, NY), Roche (Basel, Switzerland), 3M (St. Paul, MN), and Vical (San Diego, CA). She is a consultant for Novartis (Basel, Switzerland), Powdermed (Oxford, England), and Medigene (San Diego, CA) and a speaker for Merck Vaccines (Whitehouse Station, NJ). Dr. Gardella was on the speaker’s bureau of GlaxoSmithKline (Research Triangle Park, NC) in 2006. The other authors have no potential conflicts of interest to disclose.
OBJECTIVE: To describe the beliefs and practices of obstetricians related to prenatal serologic testing for HSV infection.
METHODS: A total of 265 (73% of eligible) currently practicing obstetricians in Washington State completed a 36-question mailed survey that assessed beliefs regarding genital herpes in pregnancy, neonatal herpes, serologic testing for herpes in pregnancy, and ease of testing.
RESULTS: Ninety-five percent of respondents believed genital herpes was common in reproductive-aged women, 83% believed neonatal herpes was a serious health issue, and 73% believed it warranted systematic prevention efforts; 74% discussed herpes with pregnant patients as part of prenatal care, 31% provided written materials about herpes, and 15% used serologic tests for herpes in 75% or more of their prenatal patients. Factors independently associated with routine herpes serologic testing were academic practice setting (adjusted odds ratio [aOR] 10.4, 95% confidence interval [CI] 2.8–39.1) and metropolitan practice setting (aOR 3.3, 95% CI 1.4–7.9). Beliefs that testing would cause unnecessary distress in pregnancy (aOR 0.3, 95% CI 0.1–0.7), or that testing was not worth the expense (aOR 0.1, 95% CI 0.0–0.6) were associated with not testing. Availability of serologic tests for HSV was reported to be high and was not associated with prenatal HSV testing.
CONCLUSION: Most obstetricians believe neonatal herpes prevention is important.
LEVEL OF EVIDENCE: II
Click on the links below to access all the Data Supplements for this article.
Please note that Data Supplement files may launch a viewer application outside of your web browser.
Herpes simplex virus (HSV) is a highly prevalent sexually transmitted infection with approximately 1.6 million new cases each year.1,2 Approximately 22% of pregnant women have serologic evidence of HSV-2 infection,3 and 2% of all women acquire HSV during pregnancy.4 The risk of HSV acquisition is as high as 20% for women who are HSV-2 seronegative and whose partners have HSV-2.5
Neonatal herpes, the most devastating consequence of genital herpes, occurs in 31 of 100,000 births in the Northwest6 and affects about 1,500 neonates annually in the United States.7 Current neonatal herpes prevention strategies focus on prevention of transmission from pregnant women with known genital herpes to their neonates at the time of labor.8 This mainly includes cesarean delivery for women with herpetic genital lesions at the time of labor.8 Unfortunately, this strategy misses the 70–80% of neonatal herpes cases that result from contact with HSV in the birth canal of women recently infected with genital herpes but without symptoms.6 Therefore, some experts advocate serologic testing for HSV in pregnancy to identify women at risk for acquisition during pregnancy and those at risk for genital HSV reactivation at the time of labor.9–13 Others do not recommend routine HSV serologic testing in pregnancy because of concerns about effectiveness in preventing neonatal herpes, psychological impact of HSV testing in pregnancy, and cost-effectiveness.14–18
We conducted a survey to assess the beliefs and practices of obstetricians in Washington State regarding prenatal serotesting for HSV to determine the frequency of and attitudes toward prenatal HSV testing in our state.
MATERIALS AND METHODS
An anonymous 36-question survey, adapted from a previously published survey19 and refined after pilot testing, was mailed to all members of the Washington State Chapter of the American College of Obstetricians and Gynecologists (ACOG), except for those known to be in subspecialties that do not care for prenatal patients. Readers can view the full survey online at www.greenjournal.org/cgi/content/full/110/12/1364. As an incentive to complete and return the survey, a pen and a $5 Starbucks gift card were included. The survey was mailed three times to nonresponders. The questionnaire also was offered in fax and electronic versions. Mailings occurred between September 2005 and January 2006. The study received a certificate of exemption from University of Washington Institutional Review Board.
We categorized respondents by the frequency with which they recommended serologic testing for herpes as part of prenatal care. Frequent testers were defined as those who answered “often” or “always” to the following question: “Regardless of signs or symptoms of genital herpes in pregnant women or their partners, I routinely test pregnant women for HSV antibodies as part of routine prenatal care,” and answered 75% or more to: “During the last three months, what percentage of your obstetrical patient total did you screen for HSV using a serologic test?” There was 98% agreement between these two definitions of “frequent practice”; therefore, we used 75% or more for the remainder of the analysis.
Factors potentially related to prenatal HSV testing practices were grouped into three categories: six measures of beliefs regarding prenatal HSV testing, three measures of beliefs regarding neonatal herpes, and three measures of perceptions of ease of testing. These were measured using Likert-like scales of agreement (“strongly disagree,” “disagree,” “neither agree nor disagree,” “agree,” “strongly agree”) or frequency (“never,” “sometimes,” “often,” “always”). Examples of questions of “beliefs regarding screening” included: “genital herpes is common in reproductive aged women,” “routine serologic screening for HSV in pregnant women will cause unnecessary distress among women previously unaware that they have genital herpes,” and “patient and partner histories are adequate to diagnose herpes in pregnancy.” Examples of questions of “beliefs regarding neonatal herpes” included: “neonatal herpes warrants systematic prevention approaches” and “neonatal herpes is a serious health issue.” Examples of questions regarding “ease of serologic screening” included: “routine serologic screening for HSV in pregnancy requires more effort than I have to give” and “serologic tests for HSV are readily available to me.”
We provided descriptive statistics regarding demographic information and beliefs regarding genital and neonatal herpes for all respondents. We performed both univariable and multivariable analyses to examine factors associated with prenatal HSV testing. For these analyses we included only those respondents with valid responses to the percentage of prenatal patients that they tested. For the univariable analysis, we compared the beliefs questions by serotesting category (those who tested 75% or more of prenatal patients compared with those who did not). Summary measures for each group of beliefs questions were generated and tested for internal correlation using Cronbach’s alpha coefficient. Results indicated that summary measures were not reliable because each of the three groups had an alpha coefficient of less than 0.70. Alternatively, to avoid a large number of correlated measures as predictors, we entered into a multivariable logistic regression model all demographic variables and the following factors describing beliefs selected for their strong univariable associations to represent related groups of questions: “routine HSV testing causes unnecessary distress,” “serologic tests are readily available,” and “routine prenatal HSV testing is not worth the expense” to determine the relative influences of each of these factors on prenatal HSV testing. The three beliefs variables were not significantly correlated with each other (correlation coefficient less than 0.2) and were associated with frequent prenatal HSV testing at P<.2 in univariable analysis. We included all demographic variables (Table 1) in the modeling process and performed backward stepwise elimination to select the final model of predictors of prenatal HSV testing.
Of the 467 surveys were that were mailed to potentially eligible participants, 98 were ineligible (88 not practicing prenatal care, 10 out of state or undeliverable), and 104 did not reply or refused participation, and 265 completed surveys were returned from currently practicing obstetricians. Thus, the response rate from currently practicing obstetricians in Washington State was 72% (265 of 369).
The median age of the respondents (n=265) was 48 years, the median time in practice since residency was 15 years, and the median number of deliveries attended per month per participant was 15. Fifty percent of the physicians were women, 6% were in academic practice, and 41% worked in a city. Almost all respondents agreed or strongly agreed that genital herpes was common in reproductive-aged women (95%), that genital herpes should be discussed with pregnant women (88%), and that neonatal herpes was a serious health issue (83%). Seventy-four percent (194 of 263) of respondents reported that they or their staff discussed genital herpes with their prenatal patients, and 31% (82 of 261) routinely provided written materials regarding HSV to their prenatal patients.
Of the 265 respondents, 258 provided valid responses regarding serologic testing in pregnancy. Fifteen percent of respondents with valid responses (39 of 258) reported testing for HSV antibodies in more than 75% of their prenatal population. A smaller percentage (overall 6%, 3% of infrequent testers, 21% of frequent testers) recommended HSV serologic testing for the partners of their prenatal patients, regardless of the partner’s symptoms or history of genital herpes.
Demographic and clinical factors associated with serologic testing included academic practice, working in a city, and having additional training beyond residency. Respondent gender, age, number of deliveries attended per month, recent attendance at a continuing medical education course about neonatal herpes, and having seen a case of neonatal herpes were unrelated to HSV testing in pregnancy (Table 1). Notable respondent beliefs associated with testing included beliefs that serologic testing improved the diagnosis of genital herpes, that neonatal herpes warrants systematic prevention approaches, and that routine testing for HSV in pregnancy is important to prevent neonatal herpes. Beliefs that testing would cause distress among women newly diagnosed with herpes and the expense of routine testing were associated with not testing. Eighteen percent of those who reported routine HSV testing in pregnancy and 49% of those who reported not testing were concerned that testing would cause distress. Five percent of frequent testers and 38% of infrequent testers were concerned about the cost of testing (Table 2).
Serologic tests for HSV antibodies were reported to be readily available by 85% of the infrequent testers and 100% of the frequent testers and were not associated with frequency of testing (Table 2). Of 212 who reported using serologic tests, 95 (45%) could identify the type of test their laboratory used.
In multivariable analysis, working in an academic setting was the strongest predictor of prenatal HSV testing (aOR 10.4, 95% CI 2.8–39.1, adjusted for distress, cost-effectiveness, metropolitan practice setting). Working in a city in any practice setting also was associated with frequent HSV testing in pregnancy (aOR 3.3, 95% CI 1.4–7.9, adjusted for distress, cost-effectiveness, academic practice setting). Belief that HSV testing in pregnancy caused psychological distress (aOR 0.3, 95% CI 0.1–0.7) and belief that it was not cost-effective (aOR 0.1, 95% CI 0.0–0.6) remained negatively associated with routine prenatal HSV testing after adjustment for each other and for working in a city and working in an academic setting (Table 3).
We surveyed the beliefs and practices of Washington State obstetricians to determine whether providers believed that neonatal herpes prevention was important, how many were using HSV testing routinely in practice, and how we should direct our research to answer clinically pertinent questions related to serologic testing in pregnancy. Survey results confirmed that obstetricians believed that genital and neonatal herpes were important health care concerns for their patients. Most respondents believed that genital and neonatal herpes were important enough to discuss as part of routine prenatal care, and most (73%) believed that systematic prevention of neonatal herpes was warranted. Despite these beliefs, routine serologic testing was not commonly performed.
Not surprisingly, academic practice setting was associated with routine HSV testing in pregnancy, reflecting the practice of the University of Washington where HSV testing is part of the routine prenatal testing panel. Although concerns about causing psychological distress and the cost of testing were associated with not testing, in fact, only a minority of respondents expressed concerns about these issues. Serologic tests for HSV were reported to be readily available, although most providers could not name the test their laboratory used.
The main mode of vertical transmission of HSV is neonatal contact with HSV in the maternal genital tract at the time of delivery. Women who are newly infected with genital HSV in the third trimester are at much higher risk of perinatal transmission than those with established infection.6 Current strategies to prevent neonatal herpes focus on women with established symptomatic infection and include antiviral suppression for women with recurrent lesions and cesarean delivery for women with genital lesions at the time of labor.8 Unfortunately, these methods fail to prevent 70–80% of cases of neonatal herpes because they do not address prevention of maternal HSV acquisition in pregnancy, and they do not account for the nearly 90% of HSV infections that are subclinical.4,6
Additional prevention strategies for neonatal herpes continue to be debated by experts in infectious diseases, obstetrics, epidemiology, and economics.10,15,17 Arguably, the most widely debated potential prevention strategy is routine serologic testing in pregnancy to identify women who do not have HSV antibodies and, therefore, are at risk of HSV acquisition during pregnancy. These women could be counseled about the importance of avoiding unprotected oral-genital contact or unprotected sex in the last trimester to prevent HSV infection. Additionally, partners of these women could be tested for HSV to identify serodiscordant couples. Among nonpregnant serodiscordant couples, condom use,20 antiviral suppressive therapy in the source partner,21 and disclosure of test results to partners22 each decreased the risk of HSV transmission by 50%. Use of these methods in pregnancy could significantly reduce maternal HSV acquisition and transmission to neonates.
Although routine prenatal HSV serologic testing has been part of routine prenatal care at our institution since the mid 1980s, the practice has not been endorsed by ACOG8 or Centers for Disease Control and Prevention (CDC)23 because of lack of data regarding its efficacy to prevent neonatal herpes and concerns about cost-effectiveness. Our survey results reveal an interesting discordance between beliefs of obstetricians practicing in the state of Washington about these issues and those of the groups that provide national practice guidelines. Most obstetricians who responded to our survey did not find testing-related distress or cost to be major issues. Therefore, presumably, the main reason for not testing is lack of national guidelines that recommend such. In fact, 74% of respondents reported discussing herpes in pregnancy as is recommended by ACOG, suggesting that they follow ACOG guidelines.8
Serologic testing for HSV-2 will identify pregnant women with subclinical HSV-2 infections that were previously undiagnosed. Published data suggest that pregnant women want to be tested for HSV-2 and that a new serologic diagnosis of genital herpes causes only mild transient distress. In a survey of 100 pregnant women regarding their knowledge of and their attitudes about genital herpes, 80% of women reported that they wanted to be tested for HSV in pregnancy and 76% would encourage their sexual partner to be tested.24 A similarly designed study found that pregnant women were knowledgeable about genital herpes and preferred to be tested and concluded that HSV testing should at least be offered as part of prenatal care.25 The psychosocial impact of HSV testing on individuals without a previous history of genital herpes has been well studied in nonpregnant populations. Studies of individuals presenting to sexually transmitted disease clinics, as well as primary care and adolescent clinics, and followed up at 1 week and 3 months after serologic diagnosis found no lasting psychosocial impact of detecting HSV-2 infection among those without a history of genital HSV.26,27 These studies concluded that the notion that HSV testing programs should not be implemented because of psychosocial consequences was unfounded. In our study, only seven of 39 survey respondents who routinely tested for HSV in pregnancy expressed concern that testing caused unnecessary maternal distress, suggesting that clinical experience in pregnancy may reflect that described in the nonpregnant population.
One issue brought to light by the survey was the relatively large number of obstetricians (18% of respondents) who believed that history alone was adequate to diagnose genital herpes. Recommendations by CDC23 clearly state that clinical diagnosis of genital herpes is neither sensitive nor specific and that laboratory confirmation is necessary. We were pleased that HSV antibody tests reportedly were readily available to most respondents but noted that many could not identify the type of test their laboratory used. Given the recommendation for use of type-specific tests (gG based),23 it is important for practitioners to confirm that their laboratory is using gG-based type-specific HSV serologies.
There are several limitations to this study. Responder bias is a common limitation to survey studies. Although we had over a 70% response rate, physicians who responded to this survey may have been more interested in herpes and may have been more likely to discuss herpes and include HSV testing in prenatal care. Also, the data derived from the survey is self-reported and physicians may overreport testing practices. Finally, because our survey was conducted in Washington State, the generalizability to obstetricians practicing in other states is not known. Although respondents were from heterogenous practice settings, including urban as well as rural settings, the practice patterns and beliefs regarding genital and neonatal herpes may not reflect those of providers in other states.
Routine prenatal HSV serotesting is not widely practiced in Washington State. Practicing obstetricians believe that neonatal herpes warrants systematic prevention strategies, and the majority do not believe that psychosocial sequelae of testing or cost are major issues. These findings suggest that obstetricians may be willing to incorporate HSV testing into clinical practice if national guidelines recommend such. Future efforts should focus on cost-effectiveness analyses and efficacy data to guide national recommendations toward an effective prevention strategy.
1. Armstrong GL, Schillinger J, Markowitz L, Nahmias AJ, Johnson RE, McQuillan GM, et al. Incidence of herpes simplex virus type 2 infection in the United States. Am J Epidemiol 2001;153:912–20.
2. Fleming D, McQuillan G, Johnson R, Nahmias AJ, Aral SO, Lee FK, et al. Herpes simplex virus type 2 in the United States, 1976 to 1994. N Engl J Med 1997;337:1105–11.
3. Xu F, Markowitz LE, Gottlieb SL, Berman SM. Seroprevalence of herpes simplex virus types 1 and 2 in pregnant women in the United States. Am J Obstet Gynecol 2007;196:43.e1–6.
4. Brown ZA, Selke SA, Zeh J, Kopelman J, Maslow A, Ashley RL, et al. Acquisition of herpes simplex virus during pregnancy. N Engl J Med 1997;337:509–15.
5. Gardella C, Brown Z, Wald A, Selke S, Zeh J, Morrow RA, et al. Risk factors for herpes simplex virus transmission to pregnant women: a couples study. Am J Obstet Gynecol 2005;193:1891–9.
6. Brown ZA, Wald A, Morrow RA, Selke S, Zeh J, Corey L. Effect of serologic status and cesarean delivery on transmission rates of herpes simplex virus from mother to infant. JAMA 2003;289:203–9.
7. Kimberlin DW. Neonatal herpes simplex infection. Clin Microbiol Rev 2004;17:1–13.
8. Management of herpes in pregnancy. ACOG Practice Bulletin No. 82. Obstet Gynecol 2007;109:1489–98.
9. Brown Z. Preventing herpes simplex virus transmission to the neonate. Herpes 2004;11 suppl 3:175A–86A.
10. Brown ZA. HSV-2 specific serology should be offered routinely to antenatal patients. Rev Med Virol 2000;10:141–4.
11. Baker D, Brown Z, Hollier LM, Wendel Jr, GD Hulme L, Griffiths DA, et al. Cost-effectiveness of herpes simplex virus type 2 serologic testing and antiviral therapy in pregnancy. Am J Obstet Gynecol 2004;191:2074–84.
12. Baker DA. Risk factors for herpes simplex virus transmission to pregnant women: a couples study. Am J Obstet Gynecol 2005;193:1887–8.
13. Kinghorn GR. Debate: the argument for. Should all pregnant women be offered type-specific serological screening for HSV infection? Herpes 2002;9:46–7.
14. Arvin AM. Debate: the argument against. Should all pregnant women be offered type-specific serological screening for HSV infection? Herpes 2002;9:48–50.
15. Tita AT, Grobman WA, Rouse DJ. Antenatal herpes serologic screening: an appraisal of the evidence. Obstet Gynecol 2006;108:1247–53.
16. Thung SF, Grobman WA. The cost-effectiveness of routine antenatal screening for maternal herpes simplex virus-1 and -2 antibodies. Am J Obstet Gynecol 2005;192:483–8.
17. Rouse DJ, Stringer JS. An appraisal of screening for maternal type-specific herpes simplex virus antibodies to prevent neonatal herpes. Am J Obstet Gynecol 2000;183:400–6.
18. Barnabas RV, Carabin H, Garnett GP. The potential role of suppressive therapy for sex partners in the prevention of neonatal herpes: a health economic analysis. Sex Transm Infect 2002;78:425–9.
19. LaRocco-Cockburn A, Melville J, Bell M, Katon W. Depression screening attitudes and practices among obstetrician-gynecologists. Obstet Gynecol. 101:892–8, 2003.
20. Wald A, Langenberg A, Link K, Izu AE, Ashley R, Warren T, et al. Effect of condoms on reducing the transmission of herpes simplex virus type 2 from men to women. JAMA 2001;285:3100–6.
21. Corey L, Wald A, Patel R, Sacks SL, Tyring SK, Warren T, et al. Once-daily valacyclovir to reduce the risk of transmission of genital herpes. N Engl J Med 2004;350:11–20.
22. Wald A, Krantz E, Selke S, Lairson E, Morrow RA, Zeh J. Knowledge of partners’ genital herpes protects against herpes simplex virus type 2 acquisition. J Infect Dis 2006;194:42–52.
23. Workowski KA, Berman SM. Sexually transmitted diseases treatment guidelines, 2006 [published erratum appears in MMWR Recomm Rep 2006;55:997]. MMWR Recomm Rep 2006;55 (RR-11):1–94.
24. Vonau B, Low-Beer N, Barton SE, Smith JR. Antenatal serum screening for genital herpes: a study of knowledge and attitudes of women at a central London hospital. Br J Obstet Gynaecol 1997;104:347–9.
25. Edmiston N, O’Sullivan, M, Charters D, Chuah J, Pallis L. Study of knowledge of genital herpes infection and attitudes to testing for genital herpes among antenatal clinic attendees. Aust N Z J Obstet Gynaecol 2003;43:351–3.
26. Miyai T, Turner KR, Kent CK, Klausner J. The psychosocial impact of testing individuals with no history of genital herpes for herpes simplex virus type 2. Sex Transm Dis 2004;31:517–21.
27. Rosenthal SL, Zimet GD, Leichliter JS, Stanberry LR, Fife KH, Tu W, et al. The psychosocial impact of serological diagnosis of asymptomatic herpes simplex virus type 2 infection. Sex Transm Infect 2006;82:154–8.
Figure. No caption available.
Supplemental Digital Content
© 2007 The American College of Obstetricians and Gynecologists