PREGNANCY GENITAL HERPES

Introduction

Genital herpes is a sexually transmitted disease (STD) caused by herpes simplex viruses type 1 (HSV-1) and type 2 (HSV-2). The anxiety for a pregnant woman is that she may transfer the virus to her baby during pregnancy and childbirth with potentially severe consequences. In this article measures to avoid such disaster are discussed.

Diagnosis.

Herpes simplex virus type 1 and type 2 are common infections worldwide. Herpes simplex virus type 2 is the cause of most genital herpes and is almost always sexually transmitted whereas the type 1 virus is more commonly associated with sores around the mouth. There is no exclusivity with some ulcers around the mouth being caused by the type 2 virus and some genital infections being related to the type 1 virus. These are probably related to oral sex.

Herpes on the vulva.

The labia are swollen and inflamed and there are several ulcers.

Herpes simplex infections can be diagnosed by visual inspection by a doctor. Swabs from the affected area can be taken and the virus cultured in the laboratory. When a person contracts infection, the immune system produces antibodies that can be measured in the serum (blood with its cells removed).

 

Prevalence

In the USA one adult in five has antibodies to type 2 herpes.⁰⁶⁰¹ The number of people who have been diagnosed with the condition rose from 10% to 14% between 1988 and 1999⁰⁶⁰¹ Seroprevalence of HSV-1 decreased from 62.0% in 1988-1994 to 57.7% in 1999-2004, a relative decrease of 6.9%.⁰⁶⁰¹

 

Infections

Herpes infections may be primary, secondary, recurrent or asymptomatic with viral shedding.

In a primary infection, the infection is apparent but there are as yet no antibodies to either HSV-1 or HSV-2 at the time of the outbreak indicating no prior exposure. Typically, lesions appear 2-14 days after contact. Without antiviral therapy, the lesions last for 20 days. Viral shedding lasts 12 days, with the highest rates of shedding occurring before symptoms develop and during the first half of the outbreak. Viral shedding ceases before complete resolution of the lesion. Antibody response occurs 3-4 weeks after the primary infection and is life-long. However, unlike protective antibodies to other viruses, antibodies to HSV do not prevent local recurrences. The symptoms associated with local recurrences tend to be milder than those occurring with primary disease.

The lesions of a primary infection begin as tender vesicles (blisters), which may burst to become ulcers. The vagina is commonly inflamed and the cervix is involved in 80% of patients. Pre-existing HSV-1 antibodies can alleviate clinical manifestations of subsequently acquired HSV-2. More than 75% of patients with primary genital HSV infection are asymptomatic. Asymptomatic primary HSV infections in pregnant women at term are responsible for most neonatal (newborn) HSV infections.

Symptoms associated with primary infections may be local and constitutional. Local symptoms include intense pain, dysuria (pain passing urine), itching, vaginal discharge, and lymphadenopathy (swelling of the lymph glands). Constitutional symptoms include fever, headache, nausea, malaise, and myalgia (aching muscles).

A non-primary first episode infection is a first genital HSV outbreak in a woman who has HSV type 1 antibodies. Because of the partial protection of the pre-existing antibodies, these women tend to have fewer and shorter systemic symptoms. The duration of lesions is shorter, averaging 15 days, and viral shedding lasts for approximately 7 days.

A recurrent infection is defined as a genital HSV outbreak in a woman with type 2 antibodies. Recurrent HSV outbreaks may be symptomatic or asymptomatic. Lesions typically last for 9 days, and viral shedding lasts for approximately 4 days. The viral load tends to be lower in recurrent outbreaks than with primary lesions, and shedding tends to occur during the prodrome (pre-symptomatic phase) and early stage of the clinical outbreak.  

Primary infections in pregnancy are over diagnosed. Correct classification of gestational genital herpes infections can only be accomplished when clinical evaluation is combined with viral isolation and serologic testing using a type-specific assay. Most severe first clinical episodes of genital herpes infections among women in the second and third trimesters of pregnancy are not primary infections and are not commonly associated with perinatal morbidity.^{9601, 9701}

Neonatal Herpes

Most herpes affected babies acquire the virus at the time of delivery.^{9701, 9702} Just 5% of all cases of neonatal (newborn) HSV infection result from transplacental transmission during pregnancy. In this regard, it is one of the TORCH (toxoplasmosis, rubella, cytomegalovirus, and herpes simplex) infections, which are associated with microcephaly (small head), microphthalmia (small eyes), intracranial (within the brain) calcifications, and chorioretinitis (inflammation in the eyes). The acquisition of genital herpes during pregnancy has been associated with spontaneous miscarriage, prematurity and congenital and neonatal herpes.⁹⁷⁰² 

 

Neonatal herpes is a severe systemic (involving all the body) viral infection with a high morbidity (illness) and mortality. Neonatal herpes can cause skin, eye or mouth infections, damage to the central nervous system and other internal organs and mental retardation.  It is relatively uncommon in the UK with an incidence of 1.65 per 100 000 live births annually. 9601 which compares to 11 per 100, 000 deliveries in the USA.⁹⁹⁰¹

 

Neonatal herpes may be caused by herpes simplex type 1 (HSV-1) or herpes simplex type 2 (HSV-2), as either viral type can cause genital herpes. The risks are greatest when a woman acquires a primary infection during late pregnancy, so that the baby is delivered before the development of protective maternal antibodies. Type-specific HSV serology has recently become commercially available but its use for management has not been fully evaluated.⁰⁰⁰¹

All women should be asked at their first antenatal visit if they or their partner have ever had genital herpes. Female partners of men with genital herpes, who themselves give no history of genital herpes, should be advised about reducing their risk of acquiring this infection.

Women who report a history of genital herpes can be reassured that, in the event of an HSV recurrence during pregnancy, the risk of transmission to the neonate is very small, even if genital lesions are present at delivery.^{8301, 8601, 9101, 9801, 8702} Women with no history of genital herpes may reduce their risk of acquiring herpes during pregnancy by avoiding sexual intercourse at times when their partner has an HSV recurrence. The impact of this intervention is limited because sexual transmission of HSV commonly results from sexual contact during periods of asymptomatic viral shedding.⁹²⁰²

Aciclovir

Any woman with suspected first-episode genital herpes should be referred to a genitourinary physician, who will advise on management and arrange a screen for other sexually transmitted infections. Treatment with acyclovir, an antiviral agent, should be considered for all women who develop a first episode of genital herpes during pregnancy. In non-pregnant adults, treatment of first-episode genital herpes is known to reduce the duration and severity of symptoms and decrease the duration of viral shedding. Aciclovir is well tolerated in late pregnancy and there is no clinical or laboratory evidence of maternal or fetal toxicity.⁹¹⁰¹Aciclovir has been used extensively in pregnancy and it appears to be safe.⁰⁰⁰²

The use of intravenous aciclovir may reduce the risk of neonatal herpes by minimising maternal viraemia and reducing exposure of the fetus to HSV for women who develop first episode genital herpes within six weeks of delivery.⁸³⁰¹ Invasive procedures during labour, such as fetal scalp electrode monitoring, fetal blood sampling, and instrumental deliveries, should be avoided, as there is a risk of inoculating the baby with the virus.⁹²⁰¹ One double-blind, randomized, placebo-controlled trial of acyclovir in late pregnancy for those with recurrent herpes resulted in a small reduction in the incidence of active lesions at term and the need for caesarean section.⁰³⁰¹ Valacyclovir suppression after 36 weeks of gestation also significantly reduces HSV shedding and recurrent genital herpes requiring caesarean delivery.⁰⁶⁰² In one double-blind controlled trial,⁹⁶⁰² 46 women who presented with their first episode of genital herpes during their current pregnancy were randomised at 36 weeks of gestation to receive either daily suppressive aciclovir or placebo until delivery. No infants in either group developed neonatal herpes. Suppressive acyclovir therapy reduced the need for caesarean for recurrent herpes in women whose first clinical episode of genital HSV occurred during pregnancy. A randomised controlled trial9801for women with recurrent herpes was unable to demonstrate that acyclovir in late pregnancy significantly reduces the number of caesarean sections. The conclusion was that there is little evidence to suggest that acyclovir should be used for the suppression of recurrent genital herpes infection during pregnancy.^RCOG

Where first-episode genital herpes lesions are present at the time of delivery and the baby is delivered vaginally, the risk of neonatal herpes is about 40%.8701 The risk of transmission is associated with duration of rupture of the membranes, the risk increasing considerably after the membranes had been ruptured for more than four hours.RCOG The risk of perinatal transmission depends on when in pregnancy HSV infection occurs. A large prospective study by Brown et al⁹⁷⁰² demonstrated a significant risk of neonatal herpes only when maternal HSV infection was acquired at or just before the onset of labour. Acquisition of immunity before the onset of labour, protects the baby.

Caesarean section is recommended for all women presenting with first-episode genital herpes lesions at the time of delivery, but is not indicated for women who develop first episode genital herpes lesions earlier in the pregnancy. If the first episode of genital herpes lesions within six weeks of the expected date of delivery or onset of preterm labour, elective caesarean section may be considered at term, or as indicated, and the paediatricians should be informed.^RCOG In the 1980s, it was common practice to take swabs for viral cultures weekly from women with a history of genital herpes during the last six weeks of pregnancy and if the results were positive delivery would be by elective caesarean section. This practice is no longer recommended as it has been demonstrated that antenatal swabbing did not predict the shedding of virus at the onset of labour.⁸⁶⁰¹

For women presenting with recurrent genital herpes lesions at the onset of labour, the risks to the baby of neonatal herpes are negligible with two major studies^8702,9702 showing no transmission to the  baby. In one study,⁹¹⁰¹ one baby in 34 with active recurrent herpes was affected. The practice of caesarean delivery for women with a history of genital herpes lesions that recur at delivery would result in more than 1580 excess caesarean deliveries being performed for every poor neonatal outcome prevented at a cost per neonatal herpes case averted of $2.5 million at 1993 rates.⁹³⁰¹ Furthermore, there could well be more maternal deaths by this practice than newborn babies saved. In Holland, caesarean sections have not been routinely performed for this indication since 1987 and there has been no increase in the reported incidence of neonatal herpes.⁹³⁰²