Please note: In 2003, the CTF updated its Grades of Recommendations to include an "I Recommendation" for situations where insufficient evidence exists to allow a recommendation to be made.  (Formerly, these situations were captured under a "C Recommendation".)  This change is not retroactive, and all "C Recommendations" made prior to 2003 have not been reevaluated in light of the new "I" recommendation grade.  For a discussion of these recommendation grades, please link to the 2003 article in the Canadian Medical Association Journal here.

Prevention of Neonatal Herpes Simplex

Prepared by Elaine E.L. Wang, MD, CM, FRCPC, Department of Pediatrics, University of Toronto

Objective
To make recommendations for screening high-risk pregnant women in Canada for genital herpes simplex virus (HSV) infection. This is an update of the 1989 Canadian Task Force recommendations.

Burden of Suffering
The clinical presentation in 70% of cases of neonatal herpes simplex is skin involvement consisting of cutaneous vesicles.  The clinical presentation in 20% of cases is major systematic involvement, central nervous system involvement, or both.  Less than 10% of babies with neurologic disease develop normally.  The overall mortality rate among infants with untreated infection is 65%.  In 1981 the incidence of neonatal herpes was 12 cases per 100,000 live births. High-risk women are those with a history of recurrent genital infection or active disease during the current pregnancy and those with sexual partners who have proven HSV infection.

Options
Screening options are history-taking or detection of HSV antibodies by microneutralization. Culture and clinical examination are also used. Treatment options were not evaluated.

Outcomes
Risk of transmission, clinical disease and decision to deliver vaginally or by cesarean section based on screening results.

Evidence
MEDLINE was searched to 1993 using the keywords herpes simplex, pregnancy and infant, newborn.

Values
The 13-member Task Force of experts in family medicine, geriatric medicine, pediatrics, psychiatry and epidemiology used an evidence-based method for evaluating the effectiveness of preventive health care interventions. Recommendations were not based on cost-effectiveness of options. Patient preferences were not discussed.

Background papers providing critical appraisal of the evidence and tentative recommendations prepared by the chapter author were pre-circulated to the members. Evidence for this topic was presented and deliberated upon in 1- to 2-day meetings, 2 to 3 times per year from January 1993 to June 1993. Consensus was reached on final recommendations.

Benefits, Harms, and Costs
History taking to identify women who are at high risk of transmission is unreliable. In a study of 184 cases of neonatal HSV infection only 22% of mothers reported having had a positive history of genital HSV infection and only 9% had genital lesions at delivery. Patients are often unaware of their previous active infections.

Although it is accurate, the cervical smear culture takes 3 days to complete and therefore is not useful for making decisions for women in labour.  In these cases, the penultimate culture result is used, but this has very low predictive validity for the presence of infection at the time of delivery.

Decision analysis of 9 different strategies for the prevention of neonatal HSV infection (involving physical examination, culture, and antigen testing for all or high-risk women) showed physical examination during labour to be the optimal strategy given the goal of minimizing the ratio of excess cesarean sections to cases of neonatal HSV infections. Approximately 30 excess cesarean sections would be done for each case prevented. Strategies involving screening of high-risk women would require 36 to 178 extra cesarean sections per case averted.

Economic analysis showed that the cost for each case of neonatal HSV infection prevented would be U.S. $37 million. A U. S. national screening program would prevent 1.8 cases/y.

Recommendations
Recommendation grade [A, B, C, D, E]  and level of evidence [I, II-1, II-2, II-3, III] are indicated after each recommendation. Citations in support of individual recommendations are identified in the guideline text.

Validation
This report was externally peer reviewed. The Committee on Infectious Disease of the American Academy of Pediatrics no longer supports screening. The Infectious Diseases and Immunization Committee of the Canadian Pediatric Society recommended that history and physical examination, but not culture, be used for screening, and that all infants with mothers who have genital lesions or a history of infections should be examined and followed. The 1989 U.S. Preventive Services Task Force recommended screening pregnant women with active lesions for genital HSV. The 1992 Infectious Disease Society of America recommended against serial viral cultures for women with recurrent infections and analysis of apparent lesions, and recommended for provision of education and reassurance for women with histories of genital herpes and cesarean section and culture before, or as soon as possible after, rupture of membranes for women with active genital herpes during labour.

Sponsors
The Canadian Task Force on Preventive Health Care developed this guideline with funding from Health Canada.

Selected References

Source Document
Wang E.E.L. Prevention of neonatal herpes simplex. In: Canadian Task Force on the Periodic Health Examination. Canadian Guide to Clinical Preventive Health Care. Ottawa: Health Canada, 1994; 108-14.

Other
Canadian Task Force on the Periodic Health Examination: The periodic health examination, 1989 update part 4, Intrapartum electronic fetal monitoring and prevention of neonatal herpes. Can Med Assoc J. 1989;141:1233-40.