Surrogate markers in pregnancy: should we adopt new guidance suggesting cesarean delivery for HSV in the third trimester?

EBM Focus - Volume 15, Issue 17

Reference: Obstet Gynecol. 2020 May;135(5):1236-1238

With infant mortality rates in the US still higher than in most other developed countries, interventions that might lower that rate are welcomed with open arms. A recent review showed that neonatal herpes increased from 3.4 to 5.3/10,000 births between 2009 and 2015 among Medicaid-enrolled patients. Disseminated herpes simplex virus (HSV) infection carries a 30% infant mortality rate and results in long-term neurologic sequelae in 20% of survivors. About 2% of new HSV-1 or HSV-2 infections in women occur during pregnancy and approximately 75% of women with recurrent HSV infection experience at least one episode during pregnancy. Obstetric practice has reflected the idea that active lesions during labor confer the highest risk to neonates, with longstanding recommendations to consider cesarean section in women with active lesions at the time of delivery. However, many patients with HSV are asymptomatic or have minimal symptoms and can still be contagious.

Disease-oriented evidence suggesting prolonged viral shedding after symptom resolution prompted the American College of Obstetricians and Gynecologists (ACOG) to amend its practice bulletin on the management of genital herpes in pregnancy to include Level B guidance that women with a primary or non-primary first-episode genital HSV infection during the third trimester should be offered cesarean delivery. Viral shedding may be indicated by active genital lesions or prodromal symptoms, including vulvar pain or burning. Although cesarean delivery does not entirely prevent neonatal transmission, a large prospective cohort study cited in the bulletin with 58,362 pregnant women found that cesarean delivery decreased the rate of transmission (estimated from maternal HSV serologic status) from 7.7% to 1.2% (odds ratio 0.14, 95% CI 0.02-1.08).

Revision of a clinical practice guideline based on disease-oriented evidence is wading into somewhat tricky territory. It helps to take the context and intervention into consideration. In the case of pregnant women and neonates, randomized trials are sometimes considered unethical and so we are often only able to make correlative rather than causal associations. But is it ethical to forgo clinical data altogether? In this case, a surrogate marker (maternal viral shedding) is being used as the primary determinant for a change in practice. The intervention suggested here, cesarean delivery, is common but not without some risks to mom and baby compared with vaginal delivery. ACOG must have weighed the risks of neonatal HSV with the risks of unnecessary cesarean delivery, but so must we when we consider whether to implement what are essentially consensus-based guideline recommendations.

For more information, see the topic Genital Herpes in DynaMed.

DynaMed EBM Focus Editorial Team

This EBM Focus was written by Terri Levine, PhD, Senior Medical Writer in Obstetrics and Gynecology at DynaMed. Edited by Alan Ehrlich, MD, Executive Editor at DynaMed and Associate Professor in Family Medicine at the University of Massachusetts Medical School, Dan Randall, MD, Deputy Editor for Internal Medicine at DynaMed, and Katharine DeGeorge, MD, MS, Associate Professor of Family Medicine at the University of Virginia and Clinical Editor at DynaMed.