Aetiology and natural history

Neonatal herpes is rare in the UK. It is a serious viral infection with a high morbidity and mortality. It is classified into three subgroups depending on the site of infection:

• Disease localised to skin, eye and/or mouth
• Local central nervous system (CNS) disease (encephalitis alone)
• Disseminated infection with multiple organ involvement

Approximately 50% of neonatal herpes is due to HSV-1 and 50% due to HSV-2.

Most cases of neonatal herpes result from direct contact with infected maternal secretions. In 25% of cases a possible source of postnatal infection was identified, usually a close relative of the mother. It may be a result of exposure to oro-labial herpes infection.

Transmission

Factors which affect transmission include:

• Primary or recurrent infection in the mother
• Presence of transplacental maternal neutralising antibodies
• Duration of rupture of membranes before delivery
• Use of foetal scalp electrodes
• Mode of delivery

Primary genital herpes

There is no evidence of an increased risk of spontaneous miscarriage with primary genital herpes in the first trimester or that HSV acquired in pregnancy is associated with an increased incidence of congenital abnormalities.

The neonatal risks are greatest when a woman acquires a new infection in the third trimester, particularly within 6 weeks of delivery. There is some evidence of increased perinatal morbidity and stillbirth however the data are conflicting. If a vaginal delivery ensues, the risk of neonatal herpes is very high at 41%.

Disseminated herpes is more common in preterm infants and occurs almost exclusively as a result of primary infection in the mother.

Recurrent genital herpes

• The incidence of congenital abnormalities is not increased in the presence of recurrent genital herpes infection
• In recurrent HSV the risk of neonatal herpes is low, even if lesions are present at the time of delivery (0–3% for vaginal delivery)
• Recurrent herpes at the time of delivery may cause the localised forms of neonatal herpes: both local CNS disease and skin, eye and mouth infection
• Transplacentally acquired HSV antibodies do not prevent herpes virus spreading to the brain of the neonate

Clinical features

Disease localised to skin, eye and/or mouth

• Accounts for approximately 30% of neonatal herpes infections
• Best prognosis
• With appropriate antiviral treatment, neurological and/or ocular morbidity is <2%

Local CNS disease and disseminated infection

• Accounts for approximately 70% of neonatal herpes infections
• Approximately 60% will present without skin, eye and/or mouth infection
• Infants with local CNS disease often present late (10 days - 4 weeks of age)
• With appropriate treatment:
  • Local CNS disease - mortality ~6%, neurological morbidity 70%
  • Disseminated disease - mortality ~30%, neurological morbidity 17%
• Poor outcomes have been attributed to delays between symptom onset and treatment

Neonatal infection is the result of an infection at the time of birth.

Congenital infection is due to transplacental infection in utero. This is extremely rare. It may affect the skin, eyes and CNS. There may be foetal growth restriction or foetal death.

Disseminated herpes infection in the mother

• May present with encephalitis, hepatitis, disseminated skin lesions or a combination
• Rare in adults, although more commonly reported in pregnancy, particularly if immunocompromised
• Maternal mortality associated with this condition is high

HIV-positive mothers

• Increased risk of more severe and frequent symptomatic recurrences of genital herpes during pregnancy
• Increased risk of asymptomatic shedding of HSV at term
• Co-infection with HSV and HIV increases replication of both viruses - genital reactivation of HSV may increase the risk of perinatal transmission of both HIV and HSV, although this has not been realised in practice in the UK

Diagnosis

For information on the diagnosis and management of HSV infection in the mother, please refer to BASHH HSV guidelines.

Management

Management of pregnant women with first episode genital herpes

First or second trimester acquisition (until 27 +6 weeks)

• Refer women with suspected genital herpes for assessment by a GUM physician
• Confirm diagnosis with HSV PCR
• Complete STI screen
• Do not delay treatment whilst awaiting results - manage the woman in line with her clinical condition, using aciclovir in standard doses (usually PO, IV if disseminated)
• Inform the obstetrician - if midwifery led care refer for review with an obstetrician
• Paracetamol and topical lidocaine 2% gel offer symptomatic relief
• Providing delivery is not within the next 6 weeks, the pregnancy should be managed   expectantly and vaginal delivery anticipated
• Daily suppressive aciclovir 400 mg TDS from 36 weeks reduces HSV lesions and asymptomatic shedding at term and hence the need for delivery by caesarean

 

Aciclovir is not licensed for use in pregnancy but is considered safe and well tolerated. Valaciclovir and famciclovir are not recommended as first line as there is less experience with their use. See full guideline for further details.

 

Third trimester acquisition (from 28 weeks)

• No additional monitoring of the pregnancy is required
• Do not delay treatment - manage the woman in line with her clinical condition using standard doses of aciclovir (usually PO, IV if disseminated)
• Continue daily suppressive aciclovir 400 mg TDS until delivery
• Recommend caesarean, particularly if episode is within 6 weeks of expected delivery
• Type-specific HSV antibody (IgG) testing is advisable to distinguish between primary and recurrent genital HSV infections
  • The presence of antibodies of the same type as the HSV isolated from genital swabs would confirm this episode to be a recurrence rather than a primary infection and elective caesarean would not be indicated
• Plan mode of delivery with assumption that all first episode lesions are primary genital herpes (this can be modified if test results later confirm a recurrence)
• Recommend discussion of serology results with a virologist or GUM physician

 

Management of pregnant women with recurrent genital herpes

• Recurrences usually resolve within 7–10 days without antiviral treatment
• Supportive treatment measures usually suffice e.g. saline bathing, paracetamol
• Vaginal delivery should be anticipated
• Consider daily suppressive aciclovir 400 mg TDS from 36 weeks (increased dose compared to standard suppression in non-pregnant patients)
  • Discuss the risks, benefits and alternatives with women
• Sequential PCR culture during late pregnancy or delivery is not indicated

 

Management of women with primary or recurrent genital lesions at the onset of labour

Management will be based on clinical assessment as there will not be time for confirmatory laboratory testing:

• History to ascertain if primary or recurrent episode
• Viral swab from the lesion(s) - it may influence management of the neonate
• The neonatologist should be informed

 

Primary episode

• Recommend caesarean to all women presenting with primary episode genital herpes lesions at the time of delivery, or within 6 weeks expected delivery date
  • Benefits of caesarean may reduce if the membranes have been ruptured > 4 hours - however, there may be some benefit even after this time interval
• Consider intrapartum IV aciclovir for the mother (5 mg/kg 8 hourly) and the neonate (20 mg/kg 8 hourly) if opting for vaginal delivery
• Although vaginal delivery should be avoided if possible, in women who deliver vaginally in the presence of primary genital herpes lesions, avoid invasive procedures

 

Recurrent genital herpes

• Vaginal delivery should be offered
• Caesarean section delivery can be considered
  • The risk to the mother and future pregnancies should be set against the small risk of neonatal transmission of HSV
  • The final choice of mode of delivery should be made by the mother
• Invasive procedures may be used if required
  • They may increase the risk of neonatal HSV infection but, as background risk is small, this increase is unlikely to be clinically significant
• Manage women in accordance with standard NICE intrapartum guidelines
• There is no evidence to guide the management of women with spontaneous rupture of membranes at term
  • Expediting delivery may minimise duration of potential exposure of the foetus to HSV

 

Genital herpes in preterm prelabour rupture of membranes (before 37+0 weeks)

Primary genital herpes in preterm prelabour rupture of membranes (PPROM)

• There is limited evidence to inform best obstetric practice
• Management should be guided by MDT discussion involving obstetricians, neonatologists and GUM physicians, and the gestation that PPROM occurred
• If the decision is made for immediate delivery then the anticipated benefits of caesarean will remain
• If initial conservative management, the mother should receive IV aciclovir (5 mg/kg 8 hourly)
• Consider prophylactic corticosteroids to reduce the implications of preterm delivery upon the infant
• If delivery is indicated within 6 weeks of the primary infection, delivery by caesarean may still offer some benefit despite prolonged rupture of membranes

 

Recurrent genital herpes in PPROM

• The risk of neonatal transmission is very small and may be outweighed by the morbidity and mortality associated with premature delivery
• In cases of PPROM before 34 weeks evidence suggests expectant management is appropriate, including PO aciclovir 400 mg TDS for the mother
• After 34 weeks, manage in accordance with relevant RCOG guidelines on PPROM and antenatal corticosteroid administration to reduce neonatal morbidity and mortality - it should not be influenced by the presence of recurrent genital herpes lesions

 

 

Management of HIV-positive women with HSV infection

Primary episode

Manage according to recommendations for all women with primary genital HSV infection.

 

Recurrent genital herpes

• There is some evidence that HIV-positive women with genital HSV ulceration in pregnancy are more likely to transmit HIV infection independent of other factors
• If history of genital herpes offer daily suppressive aciclovir 400 mg TDS from 32 weeks to reduce the risk of transmission of HIV, especially if vaginal delivery is planned
  • Start at earlier gestation due to increased risk of preterm labour in HIV-positive women
• The mode of delivery should be in line with the BHIVA HIV in pregnancy guideline recommendations according to obstetric factors and HIV parameters
• There is no evidence to recommend daily suppressive treatment of HSV for HIV-positive women who are HSV-1 or -2 seropositive with no history of genital herpes

 

Management of the neonate

In all cases the neonatal team should be informed.

 

Management of babies born by caesarean in mothers with primary HSV infection in the third trimester

These babies are at low risk of HSV infection. Conservative management is recommended:

• Liaise with the neonatal team
• Swabs from the neonate are not indicated
• No active treatment is required for the baby
• Normal postnatal care with neonatal examination at 24 hours of age, after which the baby can be discharged from the hospital if well and feeding established
• Educate parents regarding hand hygiene and due care to reduce risk of postnatal infection
• Advise parents to seek medical help if they have concerns regarding their baby
  • In particular, advise to look for skin, eye and mucous membrane lesions, lethargy, irritability or poor feeding

 

Management of babies born by spontaneous vaginal delivery in mothers with a primary HSV infection within the previous 6 weeks

These babies are at high risk of HSV infection. Liaise with the neonatal team.

If the baby is well:

• Send swabs of the skin, conjunctiva, oropharynx and rectum for HSV PCR
• A lumbar puncture is not necessary
• Start IV aciclovir (20 mg/kg 8 hourly) until active infection is ruled out
• Strict infection control procedures for both mother and baby
• Breastfeeding is recommended unless the mother has herpetic lesions around the nipples
• Advise parents to report any early signs of infection such as poor feeding, lethargy, fever or any suspicious lesions

 

If the baby is unwell or presents with skin lesions:

• Send swabs of skin, lesions, conjunctiva, oropharynx and rectum for HSV PCR
• A lumbar puncture should be performed even if CNS features are not present
• Start IV aciclovir (20 mg/kg 8 hourly) until active infection is ruled out

 

Management of babies born to mothers with recurrent HSV infection in pregnancy with or without active lesions at delivery

The infection risk is low. Advise conservative management of the neonate.

• Liaise with the neonatal team
• Surface swabs from the neonate are not indicated
• No active treatment is advised for the baby
• Normal postnatal care with a neonatal examination at 24 hours of age, after which the baby can be discharged from the hospital if well and feeding established
• Educate parents regarding hand hygiene and due care to reduce risk of postnatal infection
• Advise parents to seek medical help if they have concerns regarding their baby
  • In particular, advise to look for skin, eye and mucous membrane lesions, lethargy, irritability or poor feeding

 

If any concerns regarding the neonate (clinical evidence of sepsis, poor feeding):

• Liaise with the neonatal team
• In addition to considering bacterial sepsis, HSV infection should be considered
• Surface swabs and blood for HSV culture and PCR
• IV aciclovir (20 mg/kg 8 hourly) should be given while awaiting cultures
• Further management by the neonatal team according to condition of the baby and test results

 

Prevention of postnatal transmission

• Efforts to prevent postnatal transmission of HSV are important and advice should be given to the mother regarding this
• The mother and all those with herpetic lesions who may be in contact with the neonate, including staff, should practice careful hand hygiene
• Those with oral herpetic lesions (cold sores) should not kiss the neonate