Case Continued…
Because Sarah did not have a history of genital herpes, a serum sample was tested by the University of Washington Western blot. The results indicated that Sarah is seronegative for HSV-1 and HSV-2.
Sarah, who is now at 16 weeks’ gestation, returns for evaluation of new genital pain. On examination, she has several shallow ulcerations on the labia and bilateral tender inguinal adenopathy. Her husband recently had cold sores. She is anxious and would like to know if she has genital herpes and if her baby is at risk for HSV infection. You swab the base of a lesion for HSV PCR testing and start antiviral treatment.
Treating HSV infection during pregnancy
Women presenting with a new genital ulcer consistent with HSV should receive empiric antiviral treatment while awaiting confirmatory diagnostic laboratory testing, even during pregnancy. Antiviral therapy with acyclovir, valacyclovir, and famciclovir is the backbone of management of most symptomatic patients with herpes. Antiviral drugs can reduce signs and symptoms of first or recurrent genital herpes and can be used for daily suppressive therapy to prevent recurrences. These drugs do not eradicate the infection or alter the risk of frequency or severity after the drug is discontinued.
Antiviral advantages/disadvantages. Acyclovir is the least expensive drug, but valacyclovir is the most convenient therapy given its less frequent dosing. Acyclovir and valacyclovir are equally efficacious in treating first-episode genital herpes infection with respect to duration of viral shedding, time of healing, duration of pain, and time to symptom clearance. Two randomized clinical trials showed similar benefits of acyclovir and valacyclovir for suppressive therapy management of genital herpes.14,15 Only 1 study compared the efficacy of famciclovir to valacyclovir for suppression and showed that valacyclovir was more effective.16 The cost of famciclovir is usually higher, and it has the least data on use in pregnant women. Acyclovir therapy can be safely used throughout pregnancy and during breastfeeding.9 Antiviral regimens for the treatment of genital HSV in pregnant and nonpregnant women recommended by the CDC are summarized in TABLE 3.17
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Will your patient’s infant develop neonatal herpes infection?
Neonatal herpes is a potentially devastating infection that results from exposure to HSV from the maternal genital tract at vaginal delivery. Most cases occur in infants born to women who lack a history of genital herpes.18 In a large cohort study conducted in Washington State, isolation of HSV at the time of labor was strongly associated with vertical transmission (odds ratio [OR], 346).19 The risk of neonatal herpes increased among women shedding HSV-1 compared with HSV-2 (OR, 16.5). The highest risk of transmission to the neonate is in women who acquire genital herpes in a period close to the delivery (30% to 50% risk of transmission), compared with women with a prenatal history of herpes or who acquired herpes early in pregnancy (about 1% to 3% risk of transmission), most likely due to protective HSV-specific maternal antibodies and lower viral load during reactivation versus primary infection.18
Neonatal HSV-1 infection also has been reported in neonates born to women with primary HSV-1 gingivostomatitis during pregnancy; 70% of these women had oral clinical symptoms during the peripartum period.20 Potential mechanisms are exposure to infected genital secretions, direct maternal hematogenous spread, or oral shedding from close contacts.
Although prenatal HSV screening is not recommended by the CDC or USPSTF, serologic testing could be helpful when identifying appropriate pregnancy management for women with a prior history of HSV infection. It also could be beneficial in identifying women without HSV to guide counseling prevention for HSV acquisition. In patients presenting with active genital lesions, viral-specific diagnostic evaluation should be obtained. In those with a history of laboratory confirmed genital herpes, no additional testing is warranted.
Preventing neonatal herpes
There are no prevention strategies for neonatal herpes in the United States, and the incidence of neonatal herpes has not changed in several decades.10 The current treatment guidelines focus on managing women who may be at risk for HSV acquisition during pregnancy and the management of genital lesions in women during pregnancy.9,10,21
When the partner has HSV. Women who have no history of genital herpes or who are seronegative for HSV-2 should avoid intercourse during the third trimester with a partner known to have genital herpes.9 Those who have no history of orolabial herpes or who are seronegative for HSV-1 and have a seropositive partner should avoid receptive oral-genital contact and genital intercourse.9 Condoms can reduce but not eliminate the risk of HSV transmission; to effectively avoid genital herpes infection, abstinence is recommended.
When the patient has HSV. When managing the care of a pregnant woman with genital herpes evaluate for clinical symptoms and timing of infection or recurrence relative to time of delivery:
- Monitor women with a mild recurrence of HSV during the first 35 weeks of pregnancy without antiviral treatment, as most of the recurrent episodes of genital herpes are short.
- Consider antivirals for women with severe symptoms or multiple recurrences.
- Offer women with a history of genital lesions suppressive antiviral therapy at 36 weeks of gestation until delivery.21
In a meta-analysis of 7 randomized trials, 1,249 women with a history of genital herpes prior to or during pregnancy received prophylaxis with either acyclovir or valacyclovir versus placebo or no treatment at 36 weeks of gestation. Antiviral therapy reduced the risk of HSV recurrence at delivery (relative risk [RR], 0.28), cesarean delivery in those with recurrent genital herpes (RR, 0.3), and asymptomatic shedding at delivery (RR, 0.14).22 No data are available regarding the effectiveness of this approach to prevention of neonatal HSV, and case reports confirm neonatal HSV in infants born to women who received suppressive antiviral therapy at the end of pregnancy.23
When cesarean delivery is warranted. At the time of delivery, ask all women about symptoms of genital herpes, including prodromal symptoms, and examine them for genital lesions. For women with active lesions or prodromal symptoms, offer cesarean delivery at the onset of labor or rupture of membranes—this recommendation is supported by the CDC and the American College of Obstetricians and Gynecologists.9,21 The protective effect of cesarean delivery was evaluated in a large cohort study that found: among women who were shedding HSV at the time of delivery, neonates born by cesarean delivery were less likely to develop HSV infection compared with those born through vaginal delivery (1.2% vs 7.7%, respectively).19 Cesarean delivery is not indicated in patients with a history of HSV without clinical recurrence or prodrome at delivery, as such women have a very low risk of transmitting the infection to the neonate.24
Avoid transcervical antepartum obstetric procedures to reduce the risk of placenta or membrane HSV infection; however, transabdominal invasive procedures can be performed safely, even in the presence of active genital lesions.21 Intrapartum procedures that can cause fetal skin disruption, such as use of fetal scalp electrode or forceps, are risk factors for HSV transmission and should be avoided in women with a history of genital herpes.
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Case Resolved
Sarah’s genital lesion PCR results returned positive for HSV-1. She probably acquired the infection from oral-genital sex with her husband who likely has oral HSV-1, given the history of cold sores. You treat Sarah with acyclovir 400 mg 3 times per day for 7 days. At 36 weeks’ gestation, Sarah begins suppressive antiviral therapy until delivery. She spontaneously labors at 39 weeks’ gestation; at that time, she has no genital lesions and she delivers vaginally a healthy baby.
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