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Neonatal herpes is a rare but potentially serious infection, which may be associated with significant morbidity and mortality. Infection may be acquired antenatally, at the time of delivery or post-partum:
Primary maternal infection in early pregnancy may be associated with miscarriage,36 and in the second and third trimesters may be associated with preterm delivery. Rarely, primary maternal infection may result in disseminated infection of the fetus with skin lesions, chorioretinitis or microcephaly or hydrocephalus at birth.37 The long-term outlook for these infants is very poor. A minority with late intrauterine HSV infection will present at delivery with skin or eye lesions. The prognosis for successful anti-viral therapy in these infants is far better than that for newborns with more long-standing intrauterine infection.38
Antenatal recurrent disease, where HSV is not shed at delivery, is rarely associated with adverse neonatal outcomes. The risk of intrauterine fetal infection from recurrent maternal HSV infection is extremely low:39
Several factors influence the risk of a newborn acquiring HSV infection at the time of delivery, the most important of which is whether the mother has newly acquired vs recurrent genital disease. The greatest risk of perinatal transmission is when a previously seronegative woman has a primary first episode of genital herpes near or at the time of delivery. Under such circumstances the risk of neonatal HSV infection is 50%.
Although reactivation of HSV-1 is less common than that of HSV-2, there is evidence that reactivated HSV-1 may be more readily transmitted to the neonate. The same strategies are required for prevention of both HSV-1 and HSV-2.44
Transmission rates are lowest for women who acquire herpes before pregnancy, with the risk being about 0.05% for such women who have no signs or symptoms of an outbreak at delivery. Maternal antibodies cross the placenta and are protective.If lesions are present at delivery, there is a small risk of transmission of 0.25-3%.43 Specifically, the risk for transmission of reactivated HSV-2 infection appears to be less than 1%.46
Women with HIV and HSV-2 co-infection have a greater risk of transmitting HSV-2, as HSV-2 shedding is increased in HIV co-infected women.47
Of infants with proven HSV infection, 80% have no documented history of herpes infection in either the mother or her partner. The decreasing prevalence of HSV-1 in childhood increases the susceptibility of young adults to genital HSV-1 including women of reproductive age and hence increases the risk of neonatal HSV.48
Aciclovir has been used widely in pregnancy. There is less experience with valaciclovir but it is expected that valaciclovir as a prodrug of aciclovir should be safe. In the majority of situations, the benefits of antiviral therapy outweigh possible risks.
Antiviral therapy is indicated for treatment of primary and recurrent episodes as in non-pregnant women and for prophylaxis to reduce the risk of recurrence at the time of delivery. An increased frequency of dose is indicated in late pregnancy because of an increased plasma volume.
The following is a summary of the available evidence on the use of antivirals in pregnancy:
There are no established protocols for the use of antiviral medications in pregnancy, but the following regimens are frequently used:
Valaciclovir 1g bd for 7/7
There are no randomised controlled trials to guide optimal delivery management for pregnant women with genital herpes.
Caesarean section has been demonstrated to significantly reduce vertical transmission in women with primary infection in late pregnancy or at the time of delivery.
Because the risk of vertical transmission in recurrent disease is low there has been debate about the benefit of delivery by caesarean section in women who have recurrent episodes at the time of labour. In the US delivery by caesarean section in this situation is recommended but in the Netherlands there has been a policy of offering vaginal delivery for recurrent genital herpes at the time of delivery since 1987 without an apparent increase in neonatal herpes infection.
It has been shown that the presence of symptoms at delivery correlates relatively poorly with the detection of HSV from genital sites or lesions by HSV PCR. Assessment of viral shedding is based on clinical assessment.56
Caesarean section is not completely protective, as transmission of infection has occurred occasionally in the presence of intact membranes. Prolonged contact with infected secretions may further reduce the benefits of abdominal delivery.57
No definitive studies have been carried out on the relationship between the duration of rupture of membranes in the presence of clinical lesions and the transmission of HSV to the fetus. Previously, 4 hours has been suggested as a cut-off time beyond which caesarean section may be no longer beneficial. However, there is no evidence that there is a duration of premature rupture of membranes beyond which the fetus does not benefit from caesarean delivery.58
Because the risk of maternal-fetal transmission is high when primary infection is acquired within 6 weeks of delivery, maternal and neonatal aciclovir therapy should be considered if there has been membrane rupture for more than 4 hours or where a vaginal delivery is unavoidable.59
In a large prospective cohort study of women who had herpes cultures taken in labour, HSV was isolated in 202 women and, overall, neonatal transmission occurred in 10 (5%).43 Caesarean delivery significantly reduced the HSV transmission rate in women from whom HSV was isolated (1 of 85 [1.2%] caesarean vs 9 of 117 [7.7%] vaginal). Risk factors for neonatal HSV infection included:
• First-episode infection
– Of 26 first episode cases, transmission occurred in 8.
• HSV-1 vs HSV-2 isolation at the time of labour
– None of the 140 women with viral shedding due to HSV-2 reactivation infected their babies.
– HSV-1 reactivation in 2/11 women resulted in neonatal infection.
• The use of invasive monitoring.
• Premature delivery.
• Young maternal age.
There was a high caesarean section rate in those noted to have genital lesions in labour. The data from this study was pooled with two other cohorts (from the USA and Sweden) and provided further evidence that during reactivation HSV-1 may be more readily transmissible to the neonate than HSV-2. This pooled cohort study also showed that maternal HSV-1 antibody does not offer significant protection against HSV-2.60
In the Netherlands since 1987 it has been the policy not to offer women caesarean section in the presence of a recurrence at term and there has not been a resultant increase in the incidence of neonatal herpes.
In other countries, guidelines recommend that women who have signs or symptoms of a recurrent infection in labour should be offered caesarean section, but as a relative, rather than absolute, indication for abdominal delivery.58
In summary, there is a lack of robust evidence to guide management in the case of recurrent lesions at the onset of labour. Traditionally delivery by cesarean section has been offered and ideally discussion about the relative risks should occur antenatally in the event of this scenario. Because the risk of transmission is low (1-3%) some women may opt for a vaginal delivery. Factors such as prematurity, HSV-1 rather than HSV-2 and an expected long labour which may all predispose to maternal fetal transmission should be considered.
Disseminated infection from genital or oro-labial infection is rare, but may be life-threatening. Viraemia in the mother during primary infection may result in neonatal multi-organ involvement with significant mortality. The diagnosis may be delayed if vesicular skin lesions are absent or sparse.
Hospital admission and the use of intravenous aciclovir are required for severe disease in pregnancy. The diagnosis of disseminated disease should be considered in any woman presenting with systemic disease in pregnancy.
Little data is available on the management of preterm prelabour rupture of membranes in association with primary herpes simplex infection. Multidisciplinary discussion is required taking into consideration the gestation reached. Treatment with aciclovir 5mg/kg 8 hourly should be administered pending delivery. Caesarean section is considered to be beneficial despite prolonged rupture of membranes. Corticosteroids are not contraindicated.58
One study has shown that expectant management of 29 women with preterm premature rupture of membranes at 65 The mean duration of membrane rupture was 13.2 days (range 1-35 days), 45% were delivered by caesarean section and 8% received antiviral therapy for control of symptoms.
All women should be asked at the first antenatal visit if they or their partner have had genital herpes. A study of 3192 pregnant women and their partners identified that 22% of women were at risk of HSV-1 or HSV-2.56 Of 582 women susceptible to HSV-1, 14 women or 2.5% (3.5% adjusted for length of gestation) acquired HSV-1; the only independent risk factor was a history of a partner with oral herpes. Of 125 women susceptible to HSV-2 infection, 17 or 14% (20% adjusted for length of gestation) acquired HSV-2 infection. Also, the risk of becoming infected was eight times greater in relationships of a year or less, than for those in longer duration relationships. Most newly acquired infections were subclinical.
Although there is no clear evidence to support guidelines in the situation of the partner with a history of previous herpes infection, the following are recommended on theoretical grounds: Grade C
Although routine serological screening in pregnancy has been recommended by some authors, universal screening is not likely to be cost effective because of the high number needed to treat to prevent a single case of neonatal herpes.66
Note: All women with a history of genital herpes infection should be given information on postnatal neonatal surveillance. No interventions are completely protective against maternal fetal transmission.
(in consultation with a specialist)
For further management advice, see Management of Pregnant Women with Recurrent Genital Herpes, page 23.
Note: The first clinical episode may not be due to a primary infection, as previous infection may not have been recognised. Type PCR and serological testing in conjunction with clinical evaluation will help identify primary HSV in pregnancy. All results should be discussed with an expert knowledgeable in interpreting these results and who is aware of the sensitivity and specificity of available testing methods.
– It is common practice to deliver by caesarean section because of the small risk of infection in the neonate.
– However, because the fetal risk is low, this must be set against the risks to the mother of caesarean section and this is therefore regarded as a relative rather than absolute indication for caesarean section.38 Grade C
– Ideally, this scenario should be discussed with the woman early in pregnancy by the primary caregiver in conjunction with specialist advice.
– The risk of maternal fetal transmission is higher with shedding of HSV-1 than with HSV-2.
(in consultation with a specialist)
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This website is brought to you by the Sexually Transmitted Infections Education Foundation (STIEF) - an initiative funded by Te Whatu Ora.
The medical information in this website is based on the STIEF Guidelines for the Management of Genital Herpes in New Zealand. The New Zealand Ministry of Health supports the use of these clinical guidelines, developed by clinical experts and professional associations to guide clinical care in New Zealand.
The Guidelines are produced by considering available literature, both New Zealand wide and international, and by basing the medical recommendations on the evidence in the literature or reasonable supposition and opinions of medical experts.
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