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Research Letter |

Seroprevalence of Herpes Simplex Virus Type 1 and 2 Among Pregnant Women, 1989-2010 FREE

Shani Delaney, MD1; Carolyn Gardella, MD, MPH1; Misty Saracino, PhD, MPH2; Amalia Magaret, PhD2; Anna Wald, MD, MPH3
[+] Author Affiliations
1Department of Obstetrics and Gynecology, University of Washington, Seattle
2Department of Laboratory Medicine, University of Washington, Seattle
3Department of Medicine, University of Washington
JAMA. 2014;312(7):746-748. doi:10.1001/jama.2014.4359.
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Published online

Genital herpes during pregnancy frequently complicates management, although neonatal herpes, a potentially catastrophic complication, is rare.1,2 Maternal acquisition of genital herpes simplex virus (HSV) type 1 or 2 near the time of delivery accounts for most cases of neonatal herpes. Neonatal HSV incidence has been stable in recent decades, although a shift toward more HSV-1 infections has been reported.1,3 Concurrently, a decline in HSV-1 seroprevalence, but not HSV-2, has been noted among reproductive-aged women in nationwide surveys.4,5 We determined trends in the seroprevalence of HSV-1 and HSV-2 among pregnant women who delivered newborns at a single urban academic center during 2 decades.

We reviewed the charts of women who delivered at the University of Washington Medical Center between January 1989 and May 2010. Status of HSV infection was determined with the Western blot6 as part of routine prenatal tests. Women transferred for management of high-risk pregnancies but who did not have their prenatal tests repeated at our institution were excluded. Selection criteria were consistent over time. The proportion of patients with prenatal HSV serological results as part of prenatal care among all those delivering at the medical center declined slightly over the study period from 54.7% during 1989-1997 to 44.8% during 1998-2010. The University of Washington human subjects review committee provided approval with a waiver of consent.

Yearly changes in HSV-1 and HSV-2 seroprevalence were estimated with Poisson regression and a scale parameter to account for overdispersion. Models were adjusted for race/ethnicity, women’s age, parity, delivery type, and insurance status. We used SAS version 9.0 (SAS Institute Inc) and 2-sided P < .05 as statistically significant.

We identified 15 738 women with 18 993 pregnancies who had prenatal HSV serological results. The median age was 28 years (interquartile range, 23-33 years). Forty-three percent of women were white; 12%, black; 11%, Asian; 7%, Hispanic; and 27%, other or unreported; and 26% had private insurance. Forty-one percent of women were primigravid.

Overall, 9% of pregnancies involved women who were seropositive for HSV-2 only, 15% seropositive for both HSV-1 and HSV-2, 53% seropositive for HSV-1 only, and 24% seronegative for HSV. Comparing the 2 decades, HSV-1 seroprevalence decreased from 69.1% during the first decade (1989-1999) to 65.5% during 2000-2010, whereas HSV-2 seroprevalence decreased from 30.1% to 16.3%, respectively, which is a 46% relative decline.

After adjustment, we found no significant annual trend in HSV-1 seroprevalence (0.1%/year [95% CI, 0%-0.3%/year]; P = .13); however, rates of HSV-2 seroprevalence decreased significantly by 4.8%/year (95% CI, 4.3%-5.2%/year; P < .001) (Figure and Table). Seroprevalence of HSV-1 increased slightly among black women only (0.9%/year [95% CI, 0.4%-1.3%/year]; P < .001). Seroprevalence of HSV-2 decreased significantly over time among women of all races (P < .001); however, rates per year decreased substantially less for black women relative to white women (2.6%/year vs 5.5%/year, respectively; P < .001 for interaction of HSV-2 reduction by race).

Place holder to copy figure label and caption
Figure.
Rates of Herpes Simplex Virus Seroprevalence by Year, 1989-2010

Each woman was included only once during her initial pregnancy.

Graphic Jump Location
Table Graphic Jump LocationTable.  Herpes Simplex Virus (HSV) Seroprevalence Among Pregnant Women

Seroprevalence of HSV-2 among pregnant women at a single urban academic center who underwent HSV-1 and HSV-2 antibody testing substantially decreased between 1989 and 2010, and this decrease was especially pronounced among white women. As a result, racial disparities between white and black women widened, as has been noted in a population-based serological survey of persons aged 14 to 49 years.4 In contrast to that serosurvey,5 HSV-1 did not decrease overall in our study and increased slightly among black women. Differences may be the result of regional variation or the populations surveyed.

The decline in HSV-2 seroprevalence does not necessarily avert the potential for neonatal herpes. Women who are seronegative entering pregnancy and acquire HSV during late pregnancy are at higher risk for transmission of HSV to their infants than seropositive women. Temporal trends in neonatal HSV do not suggest a decline,1 although a shift toward neonatal HSV-1 has also been noted.1,3

Study limitations include participation at a single urban academic center, potentially limiting generalizability. Representativeness could be affected by the low proportion of women with HSV serological results. However, we compared women with prenatal serological results with all other women who had serological results at delivery during the first decade.3 No differences in HSV results, insurance payment, or race were noted (results available from the authors). Our findings provide new information on HSV seroprevalence specifically in the pregnant population.

Section Editor: Jody W. Zylke, MD, Senior Editor.

Corresponding Author: Shani Delaney, MD, Department of Obstetrics and Gynecology, University of Washington, 1959 NE Pacific St, Seattle, WA 98195 (delaneys@u.washington.edu).

Author Contributions: Drs Magaret and Wald had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Gardella, Wald.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Delaney, Magaret.

Critical revision of the manuscript for important intellectual content: Gardella, Saracino, Magaret, Wald.

Statistical analysis: Saracino, Magaret.

Obtained funding: Wald.

Administrative, technical, or material support: Wald.

Study supervision: Delaney, Gardella, Magaret, Wald.

Conflict of Interest Disclosures: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Wald reported receiving grant support from Genocea, Agenus, Gilead, Genentech, and Vical; and consulting fees from AiCuris, Amgen, and Eisai. No other disclosures were reported.

Funding/Support: This study was supported by grants AI-030731 and K24 AI 071113 from the National Institute of Allergy and Infectious Diseases.

Role of the Sponsor: The National Institute of Allergy and Infectious Diseases had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Previous Presentation: Presented in part at the Annual Meeting of the Infectious Disease Society for Obstetrics and Gynecology; August 11-13, 2011; Chicago, Illinois.

Morris  SR, Bauer  HM, Samuel  MC, Gallagher  D, Bolan  G.  Neonatal herpes morbidity and mortality in California, 1995-2003. Sex Transm Dis. 2008;35(1):14-18.
PubMed
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(2):203-209.
PubMed   |  Link to Article
Kropp  RY, Wong  T, Cormier  L,  et al.  Neonatal herpes simplex virus infections in Canada: results of a 3-year national prospective study. Pediatrics. 2006;117(6):1955-1962.
PubMed   |  Link to Article
Bradley  H, Markowitz  LE, Gibson  T, McQuillan  GM.  Seroprevalence of herpes simplex types 1 and 2—United States, 1999-2010. J Infect Dis. 2014;209(3):325-333.
PubMed   |  Link to Article
Fanfair  RN, Zaidi  A, Taylor  LD, Xu  F, Gottlieb  S, Markowitz  L.  Trends in seroprevalence of herpes simplex virus type 2 among non-Hispanic blacks and non-Hispanic whites aged 14 to 49 years—United States, 1988 to 2010. Sex Transm Dis. 2013;40(11):860-864.
PubMed   |  Link to Article
Ashley  RL. Militoni  J, Lee  F, Nahmias  A, Corey  L.  Comparison of Western Blot (immunoblot) and glycoprotein G-specific immunodot enzyme assay for detecting antibodies to herpes simplex types 1 and 2 in human sera. J Clin Microbiol. 1988;26(4):622-627. .
PubMed

Figures

Place holder to copy figure label and caption
Figure.
Rates of Herpes Simplex Virus Seroprevalence by Year, 1989-2010

Each woman was included only once during her initial pregnancy.

Graphic Jump Location

Tables

Table Graphic Jump LocationTable.  Herpes Simplex Virus (HSV) Seroprevalence Among Pregnant Women

References

Morris  SR, Bauer  HM, Samuel  MC, Gallagher  D, Bolan  G.  Neonatal herpes morbidity and mortality in California, 1995-2003. Sex Transm Dis. 2008;35(1):14-18.
PubMed
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(2):203-209.
PubMed   |  Link to Article
Kropp  RY, Wong  T, Cormier  L,  et al.  Neonatal herpes simplex virus infections in Canada: results of a 3-year national prospective study. Pediatrics. 2006;117(6):1955-1962.
PubMed   |  Link to Article
Bradley  H, Markowitz  LE, Gibson  T, McQuillan  GM.  Seroprevalence of herpes simplex types 1 and 2—United States, 1999-2010. J Infect Dis. 2014;209(3):325-333.
PubMed   |  Link to Article
Fanfair  RN, Zaidi  A, Taylor  LD, Xu  F, Gottlieb  S, Markowitz  L.  Trends in seroprevalence of herpes simplex virus type 2 among non-Hispanic blacks and non-Hispanic whites aged 14 to 49 years—United States, 1988 to 2010. Sex Transm Dis. 2013;40(11):860-864.
PubMed   |  Link to Article
Ashley  RL. Militoni  J, Lee  F, Nahmias  A, Corey  L.  Comparison of Western Blot (immunoblot) and glycoprotein G-specific immunodot enzyme assay for detecting antibodies to herpes simplex types 1 and 2 in human sera. J Clin Microbiol. 1988;26(4):622-627. .
PubMed
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