Background Information

For more information, see the monograph:

Herpesvirus Infections in Pregnancy

 
Pre-natal Management of Herpes Simplex Virus Infection

First episode genital herpes during pregnancy

• Disseminated or presumed maternal primary herpes simplex virus (HSV) infection should be treated with aciclovir (Category 2 recommendation)*

• For a woman presenting with a first episode of genital herpes in the third trimester, every effort should be made to characterize it serologically (e.g. primary versus non-primary)

• In women with a primary HSV infection after 34 weeks, delivery by elective Caesarean section should be considered (Category 2 recommendation).
  

Recurrent maternal herpes during pregnancy

• Aciclovir prophylaxis in late pregnancy for women with known recurrences of genital herpes is not currently recommended (Category 2 recommendation)

• The recommendation not to provide aciclovir prophylaxis in late pregnancy for women with known recurrences should be reviewed as results become available (Research need recommendation).

Pre-natal type-specific serological testing for maternal herpes simplex virus infection

• Type-specific serological testing for HSV types 1 and 2 may have value in the management of the pregnant woman and her partner. Depending on local epidemiology and test performance, it has the potential to identify:
  - Previously infected individuals
  - Those who seroconvert, if serial samples are taken
  - Discordant couples, if partners are screened

• Type-specific serological testing alone will not differentiate genital HSV-1 Infection and orolabial HSV-1 infection.
  
  *Please refer to the Appendix (page 88) of the monograph Herpesvirus Infections in Pregnancy for an explanation of the Recommendation Categories.

Management of Herpes Simplex Virus Infections at Delivery

Mode of delivery indications for Caesarean section

• In the past, Caesarean section has been used widely. Caesarean section and other management options should be discussed with the patient (Category 3 recommendation)

• Controlled trials of management policies to reduce the use of Caesarean section are required (Research need recommendation)

• Mode of delivery may be based on clinical findings at the time of delivery. (Category 2 recommendation). The presence of obvious herpetic lesions is only a relative indication for Caesarean section.

Avoidance of invasive monitoring

• Invasive monitoring of the neonate should only be used for defined obstetrical indications (Category 3 recommendation).

Management of the Neonate with Possible HSV Infection

Diagnosis of suspected or proven HSV in the neonate

• The high risk of death or neurological damage with delayed or no treatment of neonatal HSV infection requires that diagnosis be pursued promptly whenever the infection is suspected and that empiric treatment with intravenous aciclovir be initiated at the time diagnostic tests are ordered

• Neonatal herpes may occur in the absence of skin lesions. Thus, diagnostic methods are required

• Whenever neonatal HSV infection is suspected, material from skin or mucosal lesions, conjunctival swabs, mouth swabs, rectal swabs, urine and cerebrospinal fluid (CSF) should be submitted to the laboratory for virus culture and/or polymerase chain reaction (PCR) detection of HSV (Category 1 recommendation)

• Evidence of disseminated or central nervous system (CNS) infection should be sought by performing liver function tests, complete blood cell count (CBC), CSF analysis and, if there are any respiratory abnormalities, a chest X-ray (Category 1 recommendation)

• PCR analysis of the CSF for HSV DNA should be used to diagnose suspected neonatal herpes (Category 2 recommendation).

Treatment of neonatal herpes simplex virus infection

• Intravenous aciclovir (20 mg/kg every 8 hours) is recommended for neonatal HSV infection (Category 2 recommendation). Early therapy, which may improve long-term neurological outcome, is recommended (Category 1 recommendation)

• The duration of intravenous aciclovir (20 mg/kg every 8 hours) treatment should be 14 days for disease that is limited to the skin, eyes or mouth (i.e. normal CSF), and 21 days for other forms of neonatal HSV infection (i.e. abnormal CSF) (Category 1/2 recommendation). This recommendation applies to each of the clinical scenarios below

• In no circumstances should oral or topical therapy be used to treat neonatal HSV infection (Category 1 recommendation)

• The value of suppressive antiviral therapy for prevention of recurrences after the initial treatment of neonatal HSV infection has not been established (Category 2 recommendation).

Clinical Scenario 1: Infant born to a mother with clinically apparent first episode genital herpes at delivery
- Ideally, the infant should be examined by a paediatrician experienced at identifying the signs of neonatal herpes
- Specimens for virological assays (e.g. culture, PCR) should be obtained from the infant at delivery. (Follow recommendations for diagnosis in 3A)
- Prophylactic intravenous aciclovir therapy at 60 mg/kg/day in three divided doses for 14 days is recommended (Category 2 recommendation)
- If clinical signs compatible with HSV infection develop, a work-up of the CNS is indicated, including CSF examination by PCR
- If evidence of disseminated or CNS disease (i.e. abnormal CSF), the infant should be treated with intravenous aciclovir therapy (60 mg/kg/day in three divided doses) for 21 days.

Clinical scenario 2: Infant born to a mother with clinically apparent recurrent genital herpes at delivery
- Ideally, the infant should be examined by a paediatrician experienced at identifying the signs of neonatal herpes
- If lesions are present on the infant, collect specimens for routine culture
- The parents should be educated about the disease
- If the infant develops clinical signs compatible with neonatal HSV infection, collect specimens, including CSF, for virological assays (follow the detailed recommendations for diagnosis in 3A)
- The treatment with intravenous aciclovir (60 mg/kg/day in 3 divided doses for 14-21 days) started immediately (at the time diagnostic tests are ordered) pending results of the laboratory analysis and clarification of the clinical course
- If evidence of disseminated or CNS disease (i.e. abnormal CSF), the longer treatment period should be utilized (Category 2 recommendation)
- If a CSF analysis is not available, the longer treatment period should be used.

Clinical scenario 3: Infant born to mother with a history of genital herpes but no obvious lesions at delivery
- Ideally, the infant should be examined by a paediatrician experienced at identifying the signs of neonatal herpes
- In this setting parents should be educated about the signs of disease
- If any clinical signs compatible with neonatal herpes develop, specimens, including CSF, for virological assays should be obtained (follow the detailed recommendations for diagnosis in 3A)
- The treatment with intravenous aciclovir (60 mg/kg/day in 3 divided doses for 14-21 days) started immediately (at the time diagnostic tests are ordered) pending results of the laboratory analysis and clarification of the clinical course
- If evidence of disseminated or CNS disease (i.e. abnormal CSF), the longer treatment period should be utilized
- If a CSF analysis is not available, the longer treatment period should be used.

Clinical scenario 4: Infant with clinical presentation compatible with neonatal HSV infection
- Specimens for virological assays (e.g. culture, PCR) should be obtained from the infant at delivery. (Follow recommendations for diagnosis in 3A)
- A work-up of the CNS is indicated, including CSF examination by PCR
- The treatment with intravenous aciclovir (60 mg/kg/day in 3 divided doses for 14-21 days) started immediately (at the time diagnostic tests are ordered) pending results of the laboratory analysis and clarification of the clinical course
- If evidence of disseminated or CNS disease (i.e. abnormal CSF), the infant should be treated with intravenous aciclovir therapy (60 mg/kg/day in three divided doses) for 21 days.

Monitoring treatment of neonatal herpes simplex virus infection

• Infants in whom there is persistence of HSV DNA in the CSF following completion of antiviral therapy are more likely to die or suffer serious neurological impairment than infants whose post-therapy CSF specimens are PCR negative (Category 3 recommendation)

• Quantitative PCR testing of serial CSF samples may also help monitor progress and be useful as a prognostic tool (Research need recommendation).

Potential diagnostic methods

• PCR of peripheral blood mononuclear cells and plasma may also be a useful diagnostic tool (Research need recommendation)

• PCR to detect HSV DNA in dried blood spots on Guthrie cards may be useful for retrospective detection of HSV infection (Research need recommendation).

Neonatal Herpes Simplex Virus Infection - Priorities for Research

It is important to evaluate prospectively:

• PCR detection of HSV DNA in the CSF and blood

• Family counselling

• Suppressive antiviral therapy (controlled trials are in progress)

• A vaccine to prevent neonatal herpes is desirable.
  

For more information, see the monograph:

Herpesvirus Infections in Pregnancy

 
Natural History in Pregnancy

• Primary maternal cytomegalovirus (CMV) infection represents more of a risk to the fetus than recurrent maternal infection

• Primary and recurrent CMV infections in the mother are usually asymptomatic (Category 1 recommendation)

• Laboratory assays can reliably confirm primary infection but are not yet widely available

• No assays exist to detect recurrent infection in the mother that may be transmitted to the fetus.

Pre-natal Screening and Diagnosis

• Routine serological screening of pregnant women for CMV infection cannot be recommended as a standard of care at the present time. If antiviral therapy that can safely prevent or treat fetal infection is developed, then the role of maternal pre-natal screening must be reassessed. Screening some high risk women or populations may be of value now, although choices for intervention are limited (Research need recommendation)

• Fetal CMV infection can be diagnosed accurately by detection of virus in amniotic fluid by culture or PCR

• Routine screening for CMV infection during pregnancy is not indicated at present. This should be reviewed if a therapeutic intervention of proven value becomes available (Research need recommendation).

Screening for and Diagnosis of Congenital CMV Infection

• The diagnosis of congenital CMV infection should be made by the detection of virus in body fluids during the first 3 weeks of life. Urine or saliva are recommended

• Since over 90% of newborns with congenital CMV infection are asymptomatic at birth, they will not be diagnosed unless newborns are screened. Screening for congenital CMV infection can be accomplished accurately by testing saliva or urine for virus. Universal screening cannot be recommended until data supporting cost-effectiveness are available

• Isolation of CMV from urine or saliva is the gold standard for diagnosis or screening. PCR detection should work well for diagnosis, but has not been adequately evaluated for screening purposes.

Treatment and Prevention of Congenital CMV Infection

• Currently, no antiviral treatment for congenital CMV infection has been shown to decrease the frequency or severity of CNS damage in controlled clinical trials

• It is possible that the use of ganciclovir in some newborns with cytomegalic inclusion disease could decrease mortality or severe morbidity in the newborn period though this has not been demonstrated in controlled clinical trials Compassionate use of ganciclovir in newborns with life threatening or vision threatening congenital CMV infection is probably justified

• There is currently no method of proven efficacy for preventing maternal CMV infection during pregnancy.

Follow up

• Infants and children with congenital CMV infection should have audiological evaluations at least twice per year for the first 3 years of life and annually up to school age because of the risk for progressive and late onset hearing loss

• Every infant with congenital CMV infection should have at least one fundoscopic examination for retinal lesions. If lesions are present, the follow-up examinations are recommended at least annually

• Infants and children with congenital CMV infection should receive services aimed at maximizing their hearing, speech, vision, cognitive and motor functions if any impairments are found.

Research Initiatives

• Development of a vaccine to prevent maternal and congenital CMV infection

• Development of antiviral therapy which can be used safely in pregnant women with primary CMV infection to prevent transmission of virus to the fetus

• Development of antiviral therapy which can be used pre-natally to treat the infected fetus

• Development of antiviral therapy which can be used safely in newborns and infants with congenital CMV infection to decrease the frequency and severity of impairments of hearing, vision, cognitive and motor functions.
  

For more information, see the monograph:

Herpesvirus Infections in Pregnancy

 
Diagnosis - Pregnant Women

• A history of previous varicella zoster virus (VZV) infection is generally accepted as proof of immunity. But, when it can be done in a timely fashion, determination of immune status by ELISA is advisable before administration of varicella zoster immune globulin (VZIG)

• Varicella infection is generally suspected from clinical presentation, although laboratory testing may be required for confirmation

• The presence of IgG antibody in the serum in the absence of symptoms indicates previous infection. The detection of IgM with a rising IgG titre in maternal serum indicates a recent infection

• Serological testing is indicated when immunity to varicella must be determined, for example, when a past history is unreliable.

Pre-natal Diagnosis

• As the risk of congenital varicella syndrome is low (1-2%), the risk associated with the invasive pre-natal diagnostic methods (amniocentesis or cordocentesis), suggests that they are unlikely to be widely used diagnostic tools for congenital varicella syndrome

• Pre-natal diagnosis of congenital varicella syndrome following maternal primary VZV infection may allow the woman to make an informed choice about termination of pregnancy

• Ultrasound screening between 19 and 23/24 weeks of gestation is recommended for all women who have varicella in the first 21 weeks of pregnancy. If the sonographic findings are abnormal, fetal blood and amniotic fluid obtained in the 22nd to 23rd weeks of gestation should be tested for VZV DNA. Testing for VZV-specific IgM in fetal blood is not helpful (Category 2 recommendation).

Diagnosis in the Newborn

• The diagnosis of varicella infection in the newborn is usually based on clinical findings. The clinical course of varicella in newborns can vary in progression and severity.

Pre-exposure Prophylaxis - Vaccination

• Vaccination of VZV seronegative women of child-bearing age who are currently not pregnant should be considered (Category 3 recommendation).

Post-exposure Prophylaxis in Pregnant Women

• VZIG should be administered as soon as possible to the seronegative mother following exposure to VZV in the first 20 weeks of gestation. VZIG may be administered to the susceptible woman who is exposed to VZV in the third trimester to reduce the risk of chickenpox (Category 2 recommendation)

• The value of post-exposure aciclovir prophylaxis for the susceptible pregnant woman should be assessed in clinical trials (Research need recommendation).

Pregnant Women with Varicella

• The complications of varicella are more common in adults. Given the limited Registry data available, there is no apparent reason to withhold aciclovir at any time in pregnancy (Category 2 recommendation). The dosage and route of administration is determined by the severity of disease. The woman should be advised about the use of a drug unlicensed in pregnancy

• More data are required on long-term follow up of children exposed to aciclovir in utero (Research need recommendation)

• If a woman has severe or complicated disease (e.g. pneumonitis), intravenous aciclovir should be given (10 mg/kg every 8 hours for 7 days or longer) (Category 3 recommendation)

• Pregnant women with less severe disease should be treated with oral aciclovir (800 mg five time daily for 7 days) (Category 3 recommendation)

• The pregnant woman with varicella should avoid contact with all other pregnant women and neonates until her lesions are crusted.

Post-exposure Prophylaxis in the Neonate

• Administration of VZIG to the infant is advised if the mother develops varicella 7 days before or after delivery

• The neonate of a mother with active varicella should be isolated while in hospital, from birth to Day 21 (or Day 28 if the infant has been given VZIG), while neonates with congenital varicella syndrome do not need isolation from other children.

Treatment of the Neonate

• Neonates exposed to VZV should be observed closely. If they develop vesicles, they should be treated early with intravenous aciclovir

• Occasionally, neonates may develop varicella despite receiving VZIG. This is usually mild, but therapy with aciclovir should be considered.

Herpes Zoster in the Pregnant Woman

• Herpes zoster is not a risk to the fetus

• Local guidelines for treating herpes zoster in adults should be followed.

Research Initiatives for VZV Infection

• Seroreversion in vaccinees should be monitored and the need for booster immunizations evaluated

• The neurodevelopmental effect of varicella in utero and herpes zoster early in life should be assessed

• As newer antivirals become available, their clinical efficacy in treating varicella-associated conditions in pregnant women and neonates should be evaluated.