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Herpes simplex virus in pregnancy Clinical Guideline

This Clinical Guideline has been developed by the Maternity Guideline Development Group unit in
consultation with the Infectious Diseases Unit, to assist clinicians in their approach to, and care of, women
who present with herpes simplex virus (HSV) in pregnancy.

Target population for the guideline


Pregnant women booked to birth at Monash Health.

Target users of the guideline


Monash Health medical staff and midwives.

Definitions
Herpes simplex virus (HSV): Can be either type I or type II, both of which can cause genital herpes. Each
type contributes to approximately 50% of neonatal herpes infections.
Primary HSV: New acquisition of either HSV I or HSV II without previous exposure or immunoglobulin G
(IgG) antibodies to either HSV I or HSV II.
Non-primary first episode: New acquisition of a HSV serotype with previous evidence of exposure to the
other serotype. Previous infection confers some cross protection to the other serotype and outbreaks tend
to be shorter and less severe.
Recurrent HSV: Reactivation of either HSV I or II, with previous evidence of exposure to the same
serotype.
Asymptomatic viral shedding: Usually brief genital shedding. Increased in women who are co-infected
with HIV.

Background
Neonatal herpes is a rare condition associated with high morbidity and mortality. 85% of neonatal infections
are acquired during birth, 70% from asymptomatic shedding4 and the remainder occurring from postnatal
contact, transplacental transmission and ascending infection from the cervix. Most new infections (75%)
acquired during pregnancy are asymptomatic,1-3 which can make HSV a difficult condition to diagnose. The
rate of perinatal HSV transmission varies considerably depending on the clinical context, with primary HSV
in the third trimester having the highest rate of perinatal transmission (ranging from 25-50%), compared to
less than 1% with recurrent HSV.4 Risk factors for neonatal transmission include: primary HSV (as opposed
to recurrent HSV5), duration of ruptured membranes before birth, the mode of birth4, use of fetal scalp
electrodes or fetal scalp sampling4 and the trimester in which the mother is first infected.6 7 The aim of this
guideline is to minimise the risk factors for acquiring neonatal HSV while taking into consideration other
pregnancy related factors that affect maternal and fetal morbidity and mortality.

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Herpes simplex virus in pregnancy Clinical Guideline

Index of chapters

Quick reference practice recommendations

1. Prevention and screening

2. Diagnosis

3. Management of a pregnant women with a first episode of HSV

a. Antepartum – first and second trimester

b. Antepartum – third trimester

c. Intrapartum

4. Management of recurrent HSV during pregnancy

a. Antepartum

b. Intrapartum

5. Postpartum management

6. Summary of antiretroviral recommended treatment options

7. Clinical practice algorithms - ASID guidelines

1. Herpes simplex virus (HSV) : risk of vertical transmission in pregnancy

2. Herpes simplex virus (HSV): management of genital HSV in pregnancy

8. Levels of evidence

9. References

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Herpes simplex virus in pregnancy Clinical Guideline

Quick reference (summary of clinical practice recommendations)


Clinical practice recommendations Evidence
level

Routine screening of asymptomatic women is not recommended. Consensus

A diagnosis of genital HSV should be confirmed by viral polymerase chain reaction Consensus
(PCR) and by type specific HSV antibody testing (IgG to HSV-1 and HSV-2). Screening
for other sexually transmitted infections (STI) should be offered at the same time.
In relation to mode of birth, If primary HSV is contracted in the first or second trimester, III-3
women can be managed expectantly and vaginal birth can occur. However, if birth is
expected within six weeks or if primary HSV is contracted in the third trimester,
caesarean section is to be offered.
Treatment of primary HSV in the first or second trimester should include oral aciclovir Consensus
400 mg three times daily for five days (up to 10 days for severe disease).
If women contract primary HSV in the third trimester caesarean section is the III-2
recommended mode of birth, particularly for symptomatic women within 6 weeks of their
anticipated birth date, as this is associated with the highest rates (41%) of neonatal
infection.
Treatment of primary HSV in the third trimester should include oral aciclovir 400 mg Consensus
three times daily, and can continue until the woman has given birth.
Women with recurrent HSV or primary HSV in the first or second trimester should be II
offered aciclovir 400 mg three times daily from 36 weeks onwards even if
asymptomatic. This reduces the risk of clinical recurrence and asymptomatic viral
shedding at term and hence may reduce the need for caesarean section.
If preterm prelabour rupture of membranes (pPROM) occurs with primary HSV Consensus
infection and if the decision is to birth by caesarean section, the caesarean section
should be performed preferably within 4 hours as the benefit of caesarean section
reduces after that time.
If a woman labours with a known primary HSV infection in the third trimester, wherever III-2
possible avoid the use of fetal scalp blood sampling, fetal scalp electrode, artificial
rupture of the membranes and an instrumental birth unless essential to management.
If a woman has active recurrent herpes during the third trimester, she should be III-2
offered aciclovir 400 mg three times daily for five days. Symptomatic treatment including
analgesia and saline bathing can be offered as an alternative.
A caesarean section is not indicated for women with recurrent HSV but may be III-3
considered if there are active lesions or prodromal symptoms at the time of labour /
birth.
If pPROM occurs with recurrent genital herpes lesions, the overall low risk of neonatal Consensus
transmission (0-3%) should be countered by the morbidity and mortality associated with
premature birth. Before 34 weeks oral aciclovir can be given 400 mg three times daily
until the birth. After 34 weeks management should be as per the pPROM guidelines.
The paediatric team should be notified of all women giving birth with HSV, either III-2
recurrent HSV lesions at the time of birth or primary HSV acquired during the third
trimester.
Breastfeeding is recommended unless the mother has active lesions around the III-2
nipples.

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Herpes simplex virus in pregnancy Clinical Guideline

Clinical guideline

1. Prevention and screening


 Routine screening in asymptomatic women is not recommended, although it would be reasonable to
enquire about a history of HSV at the first antenatal visit.
 Routine genital HSV cultures in asymptomatic women with recurrent disease are also not
recommended.
 HSV serology testing should be considered in asymptomatic women who have been in contact with
a HSV positive partner. Women should be informed that transmission can occur even during
asymptomatic shedding.
 If a woman does not have HSV but does have a HSV positive partner, she should be counselled
about preventative measures including condom use during all sexual intercourse, abstinence during
the third trimester or if genital lesions are present and avoidance of oral intercourse if lesions are
present on either the lips or genitals.

2. Diagnosis
 A diagnosis of any active lesions should be confirmed by viral polymerase chain reaction (PCR).
Antibody serology testing to detect the presence of HSV antibodies can help differentiate between
recurrent and primary infections. A concurrent STI screen should be performed.
 It can be difficult to distinguish between primary and secondary infections clinically, and type specific
HSV antibody testing (IgG to HSV-1 and HSV-2) is recommended to distinguish between primary,
recurrent, and a primary episode of a new HSV type. Until these results return, treatment should be
as if it is a primary infection.

3. Management of a pregnant woman with a first episode of HSV

a. Antepartum – first and second trimester


 Women with a primary infection should be referred for ongoing specialist obstetric care in order to
facilitate testing, treatment and discussion about the mode of birth.
 Women can be counselled that infection will not increase the spontaneous miscarriage rate or the
rate of congenital abnormalities. Pregnancy should be managed expectantly, unless birth is
anticipated within six weeks, and a vaginal birth can occur if there are no active herpetic lesions at
the time.
 Treatment should involve oral aciclovir 400 mg three times daily for five days (up to 10 days for
severe disease), which reduces the duration and severity of symptoms and viral shedding. Women
can be counselled that this is not associated with an increase in birth defects or long-term adverse
maternal or neonatal outcomes.
 Women with primary HSV in the first or second trimester should be offered aciclovir 400 mg three
times daily from 36 weeks onwards for prophylaxis even if their symptoms have resolved.
 Paracetamol and topical lignocaine can be used for symptomatic relief. Ice packs and voiding while
sitting in warm water and genital hygiene can be recommended.

b. Antepartum – third trimester


 Although some evidence indicates an increased rate of preterm labour and low birthweight, data are
conflicting and no additional monitoring in pregnancy is recommended.
 Treatment should involve oral aciclovir 400 mg three times daily, continuing until the birth.
 Paracetamol and topical lignocaine can be used for symptomatic relief. Ice packs, voiding while
sitting in warm water and genital hygiene can be recommended
 Caesarean section is recommended for all women with primary HSV in the third trimester,
particularly for those with symptoms within 6 weeks of their anticipated birth, as this is associated
with the highest rate of neonatal infection (25-50%)4
 If preterm pre-labour rupture of membranes (pPROM) occurs in the setting of recent primary HSV

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infection a caesarean section should be performed if appropriate in the clinical context. If birth
occurs within 6 weeks of the initial infection, caesarean section may still be beneficial, but there is
some evidence to suggest that the benefits of caesarean section are reduced if over four hours has
elapsed since the membranes ruptured and if the woman is on antiviral therapy.
 There is limited evidence to inform best practice in the setting of pPROM, primary HSV and
conservative management. Oral aciclovir may be considered although there is no evidence of
benefit.6

c. Intrapartum
 The paediatric team should be informed if primary HSV has been acquired in the third trimester.
 If active lesions are present and there is doubt as to whether it is a primary or recurrent lesion, a
viral swab and serology testing should be taken as it will affect neonatal management but it should
be treated as a primary infection.
 If a woman chooses to have a vaginal birth she should be counselled that in the setting of primary
lesions being present at birth, the risk of neonatal herpes is approximately 40%.
 If a woman chooses to have a vaginal birth and has active lesions from a primary HSV infection she
should receive 5 mg/kg intravenous aciclovir every 8 hours until the birth. If there are no active
lesions and she is on oral aciclovir then IV aciclovir is not warranted.
 If a woman gives birth vaginally with a known primary HSV infection in the third trimester, the use of
fetal blood scalp sampling, fetal scalp electrodes, artificial rupture of the membranes and
instrumental birth should be avoided unless essential to management.
 If a woman presents with term spontaneous rupture of the membranes, an expedited caesarean
section should be offered to minimise the duration of potential fetal exposure, and 5 mg/kg
intravenous aciclovir given every 8 hours until the baby is born.

4. Management of recurrent HSV during pregnancy

a. Antepartum
 Women with recurrent HSV should be referred to specialist obstetric care in order to facilitate
testing and discussion about the mode of birth. Women with recurrent HSV may continue midwife
or collaborative care unless genital herpes are active late in pregnancy (as per referral guidelines).
 If women have active recurrent herpes during the third trimester they should be offered aciclovir
400 mg three times daily for 5 days. However, recurrent episodes are usually short and self-limiting
without antiviral therapy, so supportive treatment (saline baths, analgesia, etc.) should be offered as
an alternative and the risks and benefits discussed with the woman.
 Aciclovir 400 mg three times daily as a prophylactic dose from 36 weeks gestation should be offered
for all women with a previous diagnosis of HSV with the aim of reducing asymptomatic viral
shedding and recurrences at the time of birth.
 A caesarean section is not indicated for women with recurrent HSV if there are no active lesions or
prodromal symptoms. However elective caesarean section should be discussed if there are active
lesions or prodromal symptoms at the onset of labour, or if there is a positive viral culture, even
without the presence of active lesions.
 If an active recurrent lesion is present, the overall risk of transmission is low (1-3%). However, the
type of HSV affects the neonatal transmission rate. HSV 1 has a 15% neonatal conversion rate if
present in the genital tract during birth, while HSV 2 has a <0.01% conversion rate. Therefore it
would be reasonable to take a viral swab and identify the type (I or II) in order to better counsel
women.
 If pPROM occurs with recurrent genital herpes lesions, the low risk of neonatal transmission should
be counteracted by the morbidity and mortality associated with premature birth. Oral aciclovir 400
mg three times daily should be given until the birth if pPROM occurs before 34 weeks. After 34
weeks the management should be as per the pPROM guideline and should not be significantly
influenced by recurrent genital herpes lesions.

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b. Intrapartum
 The paediatric team should be informed if active lesions are present at the time of birth.
 If active lesions are present and there is doubt as to whether it is a primary or recurrent lesion, a
viral swab and serology testing should be taken as it will affect neonatal management but it should
be treated as a primary infection.
 Women presenting in spontaneous labour with known recurrent HSV should be informed that:
o If no active lesions are present the risk to the baby of neonatal herpes from a vaginal birth is
low (0-3%) and a vaginal birth should be offered.
o If HSV is detected in the genital tract the risk of transmission is 1-3%. The risk is greater for
recurrent genital HSV 1 (15%) compared to recurrent genital HSV 2 infection (< 0.01%).
 Fetal blood scalp sampling, fetal scalp electrodes, artificial rupture of the membranes and
instrumental birth may increase the risk of neonatal HSV infection and should be avoided if possible.
However, given the small background risk, they may be used if essential to management.
 If a woman presents with term spontaneous rupture of the membranes, an expedited birth may be
attempted to minimise the duration of potential fetal exposure.

5. Postpartum management
 The paediatric team should be notified of all babies born of mothers with active recurrent HSV at
the time of giving birth or primary HSV acquired during the third trimester.
 Breastfeeding is recommended unless the mother has active lesions around the nipples.
 Both the mother and all visitors with herpetic lesions (including oral lesions) should practice careful
hand hygiene, and be advised if oral lesions are present not to kiss the baby.

6. Summary of antiretroviral recommended treatment options for herpes simplex virus2


A 2008 Cochrane review found that antiviral prophylaxis led to a significant reduction in the recurrence
of genital herpes at birth (RR 0.28, 95% CI 0.19-0.43) and a reduction in the caesarean section rate (RR
0.30, 95% CI 0.20 to 0.45). However, there is insufficient evidence to determine if antiviral prophylaxis
reduces the incidence of neonatal herpes.8
Aciclovir and valaciclovir are considered category B3 drugs in Australia, meaning that no increase in the
frequency of malformations or other direct or indirect harmful effects on the human fetus have been
observed but that animal studies have shown evidence of an increased occurrence of fetal damage, the
significance of which is uncertain in humans. However, a population cohort study of 80,0000 live births
in Denmark did not note any differences (1000 babies exposed to aciclovir, 181 to valaciclovir). 9
Indication Aciclovir
Treatment of primary first episode in 400 mg orally three times daily for 5 days.
first or second trimester
Treatment of primary first episode in 400 mg three times daily, and can continue until the birth.
third trimester
Treatment of recurrent episodes 400 mg orally three times daily for 5 days should be offered,
but this should be in a risk benefit discussion with supportive
therapy as an alternative.
Prophylaxis for all women (36 weeks 400 mg orally three times daily until the birth.
onwards)
pPROM Oral aciclovir may be considered if not in labour although there
is no evidence of benefit.6

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7. Algorithms
Reproduced with permission from the Australasian Society for Infectious Diseases (ASID) Inc.

7.1 Herpes simplex virus (HSV): risk of vertical transmission in pregnancy

(ASID guidelines4 https://www.asid.net.au/documents/item/368 Page 28 )

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7.2 Herpes simplex virus (HSV): management of genital HSV in pregnancy


Reproduced with permission from Australasian Society for Infectious Diseases (ASID) Inc.

Algorithm from ASID guidelines https://www.asid.net.au/documents/item/368 Page 29

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8. Levels of evidence10
Level Intervention Transfer from RCOG
Green-top Guideline,
where applicable
I A systematic review of level II studies. 1a

II A randomised controlled trial. Ib


III-1 A pseudo-randomised controlled trial. IIa
III-2 A comparative study with concurrent controls: IIb
 Non-randomised experimental trial.
 Cohort study.
 Case-control study.
Interrupted time series without a parallel control group.
III-3 A comparative study without concurrent controls: III
 Historical control study.
 Two or more single arm study.
Interrupted time series without a parallel control group.
IV Case series with either post-test or pre-test outcomes. III

*Refer to full reference for the evidence hierarchy of prognosis, aetiology and screening interventions.

Consensus: An additional level of evidence used here, for example, from IV


published guidelines that have involved extensive
consultation and deliberation, where specific
recommendations have been agreed upon by consensus of
the contributors.

9. References

1. Ural S, Peng T. Genital herpes in pregnancy. Medscape 2015.


2. South Australia Perinatal Practice Guidelines. Genital herpes simplex (HSV) infection in pregnancy
Department of Health, Government of South Australia, 2013.
3. New Zealand Herpes Foundation. Guidelines for the Management of Genital Herpes in New
Zealand. Genital Herpes in Pregnancy: New Zealand Herpes Foundation, 2013:24-39.
4. Australasian Society for Infectious Diseases. Management of Perinatal Infections. Herpes Simplex
Virus Sydney: Australiasian Society for Infectious Diseases (ASID), 2014:27-32.
5. King Edward Memorial Hospital. Herpes simplex in pregnancy: King Edward Memorial Hospital
2014.
6. Royal College of Obstetricians & Gynaecologists. Management of Genital Herpes in Pregnancy:
Royal College of Obstetricians & Gynaecologists (RCOG), 2014.
7. Stratface G, Selmin A, Vincenzo Z, et al. Herpes Simplex Virus Infection in Pregnancy. Infectious
Diseases in Obstetrics and Gynecology 2012;2012:385697.
8. Hollier L, Wendel G. Third trimester antiviral prophylaxis for preventing maternal genital herpes
simplex virus (HSV) recurrences and neonatal infection (Review). The Cochrane Library 2008;2008
(1):CD004946.
9. Pasternak B. Use of acyclovir, valacyclovir, and famiclovir in the first trimester of pregnancy and the
risk of birth defects. . JAMA 2010;304(8):859-66.
10. Merlin T, Weston A, Tooher R. Extending an evidence hierarchy to include topics other than
treatment: revising the Australian 'levels of evidence'. BMC Medical Research Methodology 2009; 9:
doi:10.1186/471-2288-9-34.

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Herpes simplex virus in pregnancy Clinical Guideline

This guideline is associated with the following procedures and guidelines:


(alphabetically listed)
 Assisted Operative vaginal birth forceps and ventouse
 Fetal blood sampling
 Fetal surveillance intrapartum
 GP obstetrician pregnancy care inclusion / exclusion / referral
 Healthcare Workers with Infectious Diseases
 Induction of labour (IOL) cervical ripening balloon catheter
 Midwifery primary carer booking inclusion / exclusion criteria
 Midwifery primary carer referral to obstetric care criteria
 Precautions Transmission Based
 Preterm pre-labour rupture of membranes (pPROM)
 Term pre-labour rupture of membranes (PROM)
Keywords or tags
Herpes Simplex Virus, HSV, HSV-1, HSV-2, Infectious diseases in pregnancy, sexually transmitted
infections, STI

Document Management
Unit/service responsible: Monash Women’s Maternity Guideline Development Group
Staff consulted in the development/endorsement of the clinical guideline occurred with:
Natasha Pritchard Obstetric Resident | Monash Health
Amanda Ward Obstetric Registrar | Monash Health
Assoc Prof Michelle Giles Infectious Diseases Physician | Monash Health
Nicole Dirnbauer Quality Use of Medicines Pharmacist | Monash Health
Maternity Executive Committee 2015 | Monash Health
Policy supported: Evidence-Based Clinical Care (Operational Policy)
Executive sponsor: Chief Operating Officer.
If this is a hard copy it might not be the latest version of this document. Please see the Monash Health site for
current documents.
Disclaimer
The maternity clinical practice procedures and guidelines have been developed having regard to general circumstances. It is the responsibility of
every clinician to take account of both the particular circumstances of each case and the application of these procedures and guidelines. In
particular, clinical management must always be responsive to the needs of the individual woman and particular circumstances of each pregnancy.
These procedures and guidelines have been developed in light of information available to the authors at the time of preparation. It is the
responsibility of each clinician to have regard to relevant information, research or material which may have been published or become available
subsequently. Please check this site regularly for the most current version.

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