Hindawi Publishing Corporation

Infectious Diseases in Obstetrics and Gynecology

Volume 2012, Article ID 385697, 6 pages
doi:10.1155/2012/385697

Review Article
Herpes Simplex Virus Infection in Pregnancy

Gianluca Straface,1 Alessia Selmin,1 Vincenzo Zanardo,1 Marco De Santis,2

Alfredo Ercoli,1 and Giovanni Scambia2
1 Department of Obstetrics and Gynaecology Policlinico Abano Terme, 35031 Abano Terme (PD), Italy
2 Department of Obstetrics and Gynaecology, Catholic University of Sacred Heart, 00100 Roma, Italy

Correspondence should be addressed to Gianluca Straface, [email protected]

Received 11 January 2012; Accepted 12 February 2012

Academic Editor: Francesco De Seta

Copyright © 2012 Gianluca Straface et al. This is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly
cited.

Infection with herpes simplex is one of the most common sexually transmitted infections. Because the infection is common in
women of reproductive age it can be contracted and transmitted to the fetus during pregnancy and the newborn. Herpes simplex
virus is an important cause of neonatal infection, which can lead to death or long-term disabilities. Rarely in the uterus, it occurs
frequently during the transmission delivery. The greatest risk of transmission to the fetus and the newborn occurs in case of an
initial maternal infection contracted in the second half of pregnancy. The risk of transmission of maternal-fetal-neonatal herpes
simplex can be decreased by performing a treatment with antiviral drugs or resorting to a caesarean section in some specific cases.
The purpose of this paper is to provide recommendations on management of herpes simplex infections in pregnancy and strategies
to prevent transmission from mother to fetus.

1. Introduction HSV-2 may cause eye or skin lesions, meningoencephalitis,

disseminated infections, or foetal malformations.
Herpes simplex virus (HSV) is an ubiquitous, enveloped,
and doublestranded DNA virus, belonging to the family of
Herpesviridae transmitted across mucosal membranes and 2. Epidemiology
nonintact skin, that migrate to nerve tissues, where they per-
In recent years, genital herpes has become an increasing
sist in a latent state. HSV-1 predominates in orofacial lesions,
common sexually transmitted infection. From the late 1970s,
and it is typically found in the trigeminal ganglia, whereas
HSV-2 seroprevalence has increased by 30%, resulting that
HSV-2 is most commonly found in the lumbosacral ganglia
one out of five adults is infected [4, 5].
[1]. Nevertheless these viruses can infect both orofacial areas
and the genital tract. In some developed countries type 1 has HSV seroprevalence in patients with STD varies from
recently emerged as the prominent causative agent in genital 17% to 40% (6% in the general population and 14% in
lesions. Changes in sexual behaviours of young adults may pregnant women) [6, 7].
partly explain its higher incidence [2, 3]. Age and sex are important risk factors associated with the
A first primary infection develops when a susceptible acquisition of genital HSV-2 infection. In fact, the prevalence
person (lacking of preexisting HSV-1 and HSV-2 antibodies) of HSV infection rises with age, reaching the maximum
is exposed to HSV. around 40 years [4]. This infection appears related to the
Indeed, a first nonprimary episode occurs when a person number of sexual partners, and regarding sex it is more fre-
with preexisting HSV antibodies (against type 1 or 2) expe- quent in women than in men [8, 9].
riences a first episode with the opposite HSV type. In addition, ethnicity, poverty, cocaine abuse, earlier
Recurrent infection occurs in a person with preexisting onset of sexual activity, sexual behavior, and bacterial vagino-
antibodies against the same HSV type [1]. Infections during sis can facilitate a woman’s risk of infection before pregnancy
pregnancy may be transmitted to newborns: HSV-1 and [10, 11].
2 Infectious Diseases in Obstetrics and Gynecology

Regarding pregnant population, there is a high preva- either serologically or with viral culture. Isolation of HSV
lence of genital herpes. Among Italian pregnant women, the in cell culture is the preferred virologic test for patients
seroprevalence varies from 7.6% to 8.4% seroprevalence [9]. who seek medical treatment for genital ulcers or other
Nevertheless it is lower than that reported among pregnant mucocutaneous lesions and allows differentiation of the type
women in other countries. For example, in US, approxi- of virus (HSV-1 versus HSV-2) [21]. The sensitivity of this
mately 22% of pregnant women are infected with HSV-2, test is limited because of several issues related to sampling
and 2% of women acquire genital herpes during pregnancy, and transportation of the specimen. Additionally, as the
placing their newborn at risk for herpes infection. In Italy, lesions heal, they are less likely to be culture positive [21].
the number of women who acquire HSV infection during Thus, a positive genital culture provides conclusive evidence
pregnancy is about 3%. The acquisition of genital herpes of genital HSV infection; however, a negative result does not
during pregnancy has been associated with spontaneous exclude the presence of infection. Polymerase chain reaction
abortion, intrauterine growth retardation, preterm labour, techniques involve the amplification of particular sequences
and congenital and neonatal herpes infections [12–14]. of DNA or RNA before detection and can thus detect
The risk of neonatal infection varies from 30% to evidence of viral DNA at low concentrations. In one very
50% for HSV infections that onset in late pregnancy (last large study, PCR results were three to five times more likely to
trimester), whereas early pregnancy infection carries a risk of be positive than were cultures. Cultures were more likely to
about 1%. When primary HSV infection occurs during late be positive at increasing concentrations of virus. Polymerase
pregnancy, there is not adequate time to develop antibodies chain reaction techniques are commercially available and
needed to suppress viral replication before labour. About can differentiate between HSV-1 and HSV-2. Polymerase
85% of perinatal transmission occurs during the intrapartum chain reaction provides increased sensitivity over culture and
period while transmission of HSV from mother to foetus may ultimately replace culture as the standard of care for
during pregnancy is less common. Moreover, studies in HIV- diagnosis [22].
infected pregnant women show that coinfection with HSV At the first prenatal visit also the partner history should
increases significantly the risk of perinatal HIV transmission be investigated. In case of positive history in the male
above all in women who had a clinical diagnosis of genital partner, he should be strongly advised to have no oral and
herpes during pregnancy [15–17]. sexual intercourse at the time of recurrence in order to
The newborn could be also infected by HSV-1, that may avoid infection (in particular during the third trimester of
represent almost one-third of all new genital HSV diagnoses. gestation). Moreover, use of condoms throughout pregnancy
should be recommended to minimize the risk of viral
acquisition, although the male partner has no active lesions
3. Diagnosis [23].

Primary symptomatic genital herpes, that occurs after an 4. Congenital and Neonatal Infection
incubation of a period of 2–20 days, lasts up to 21 days
[4, 18]. Within women it causes blistering and ulceration Itis necessary to distinguish between congenital infection and
of the external genitalia and cervix leading to vulval pain, neonatal infection with HSV. In fact, HSV infection of the
dysuria, vaginal discharge, and local lymphadenopathy [18]. newborn can be acquired during pregnancy, intrapartum
Vesicular and ulcerative lesions of the internal thigh, but- and postnatally. The mother is the most common source
tocks, perineum or in perianal skin are also observed. Both of infection for the first two routes of viral transmission.
in man and in woman primary infection may be complicated Congenital infection is very rare due to the acquisition of the
by systemic symptoms such as fever, headache, myalgia (38% virus in utero; it comes to the neonatal HSV infection when
in men, 68% in women), and occasional meningitis and by the appearances of the lesions are more than 48 hours after
autonomic neuropathy resulting in urinary retention, mainly birth [24, 25].
in women [9, 11]. Intrauterine HSV infection accounts for 5% of HSV
All suspected herpes virus infections should be con- infections in neonates. The highest risk of intrauterine in-
firmed through viral or serological testing. A diagnosis of fection has been observed in pregnant (about 50%) who
genital herpes based on the clinical presentation alone has a develop disseminated HSV infections and 90% of those are
sensitivity of 40% and specificity of 99% and a false-positive related to HSV-2. Both primary and recurrent maternal
rate of 20% [19]. infection can result in congenital disease, even if the risk after
The tests used to confirm the presence of HSV infection recurrent infection is small.
can be divided into two basic groups: (1) viral detection tech- Intrauterine viral transmission is highest during the first
niques and (2) antibody detection techniques. Primary viral 20 weeks of gestation leading to abortion, stillbirth, and
DNA testing techniques are viral culture and HSV antigen congenital anomalies. The perinatal mortality is 50% [24].
detection by polymerase chain reaction (PCR). The antibody In 85–90% of neonatal HSV infections, HSV is acquired
detection techniques include the use of both laboratory- at the time of delivery and 5–10% are caused by early post-
based and point-of-care serologic tests to detect the presence natal viral acquisition. A percentage of 70–85% of neonatal
of antibodies to either HSV-1 or HSV-2. With viral detection HSV infections are caused by HSV-2, whereas the remaining
techniques, negative results do not rule out the presence of cases are due to HSV-1. The HSV-2 infection carries a graver
infection [20]. The diagnosis of HSV should be confirmed prognosis than that caused by HSV-1 [26].
Infectious Diseases in Obstetrics and Gynecology 3

The disease transmission to the newborn is dependent on multiorgan involvement mortality, is 30% and the percentage
the type of maternal genital infection at the time of delivery. of sequelae of 20% [28, 32].
In fact, neonatal herpes is much more frequent (50%)
in babies from mothers with a primary HSV infection with 5. Management of First Infection with
respect to babies from mothers with recurrent HSV infection HSV in Pregnancy
(<3%). However, most neonatal HSV infections (about 70%)
result from exposure to asymptomatic genital HSV infection In 2008, the Society of Obstetricians and Gynaecologists of
in the mother near delivery [27]. Canada published guidelines on the management of HSV in
The prolonged rupture of membranes is a risk factor for pregnancy [33].
acquisition of neonatal infection [28]. Congenital intrauter- The risk of infection to the infant appears to be higher
ine infection is characterized by skin vesicles or scarring, eye when the first infection occurs during the third trimester of
lesions (chorioretinitis, microphthalmia, and cataract), neu- pregnancy. In this case there may not be sufficient time for
rologic damage (intracranial calcifications, microcephaly, the development of maternal IgG and their passage to the
seizures, and encephalomalacia), growth retardation, and fetus, and the risk of neonatal infection is 30 to 50% [34].
psychomotor development. Infants infected intrapartum or If infection occurs in the first trimester of pregnancy, this
postnatally by HSV can be divided into three major cate- seems to be linked to an increase in spontaneous abortions
gories: and cases of intrauterine fetal growth restriction. Only in rare
cases there is the transmission of the virus transplacentally,
(1) HSV disease localized to the skin, eye, and/or mouth resulting in a very severe congenital infection that can occur
(SEM); this syndrome is associated with a low mor- with microcephaly, hepatosplenomegaly, intrauterine fetal
tality but it has a significant morbidity, and it may death, and IUGR. The use of antivirals is also permitted in
progress to encephalitis or disseminated disease if left the first trimester of pregnancy if the mother’s injuries are
untreated; particularly serious. At the moment there are enough data to
(2) HSV encephalitis with or without skin, eye, and/or define dell’acyclovir safe to use during pregnancy [35].
mouth involvement which causes neurologic mor- When primary infection is acquired during the first
bidity among the majority of survivors; two trimesters of pregnancy, it is advisable to carry out
(3) disseminated HSV which manifests as severe multi- sequential viral cultures on genital secretions from 32th week
organ dysfunction (including central nervous system, of gestation [36]. Both viral culture that the nucleic acid
liver, lung, brain, adrenals, skin, eye, and/or mouth) amplification tests (NAATs) are considered as a test of choice
and has a mortality risk that exceeds 80% in absence for symptomatic patients. As in Western Europe and the
of therapy [27, 28]. United States, there are no comprehensively validated and
approved commercial NAATs available for detection of HSV
At diagnosis, symptoms are found with the following in many eastern European countries. However, some NAATs
frequency: skin vesicles 68%, fever 39%, lethargy 38%, sei- for HSV detection have been developed and are available in
zures 27%, conjunctivitis 19%, pneumonia 13%, and dis- Eastern Europe, but have not been validated against their
seminated intravascular coagulation 11%. Symptoms may internationally acknowledged analogues.
occasionally be present at birth, but occur in 60% later than However, if two consecutive cultures result negative and
5 days after birth and sometimes are present after 4–6 weeks there are no active herpetic genital lesions at the time of
of life [21]. delivery, it is possible to perform a vaginal delivery. If ser-
Localized infections have been found in 50% of the oconversion is completed at the time of delivery, caesarean
affected neonates, involvement of the central nervous system section is not required since the risk of HSV transmission
(CNS) in 33%, and disseminated infections in 17% of to the foetus is low, and the neonate should be protected by
the cases [19, 23]. Several studies have demonstrated that maternal antibodies.
disseminated HSV infections are characterized mainly by If primary genital infection is acquired during the third
liver and adrenals failure associated with shock symptoms trimester of pregnancy, the optimal way of proceeding is not
and disseminated intravascular coagulopathy [29–31]. Other well defined. Most guidelines propose caesarean section for
symptoms of HSV disseminated infection include irritability, women developing a primary clinical infection within the
seizures, respiratory distress, jaundice, and frequently the last 4–6 weeks of gestation, because they cannot complete
characteristic vesicular exanthem that is often considered their seroconversion prior to the time of delivery, and
pathognomonic for infection. However, over 20% of infants therefore they could infect the neonates. When vaginal
with disseminated infection do not develop skin vesicles delivery is irreversible, since the risk of vertical transmission
during the course of their illness. Encephalitis appears to be is high (41%), a maternal and neonatal intravenous acyclovir
a common component of this infection form, occurring in therapy is recommended [37–39].
about 60–75% of infants with disseminated HSV infection.
Mortality in the absence of therapy exceeds 80% [29]. 6. Management of Infection Recurrent
The prognosis of infants with disseminated HSV disease HSV in Pregnancy.
or neurological manifestations is poor. The mortality in
cases with neurological involvement by about 5% with 50% A pregnant woman with HSV lesion that has already
of children with neurological sequelae, while in cases with presented a first infection in the past has circulating IgG,
4 Infectious Diseases in Obstetrics and Gynecology

Table 1: Recommended doses of antiviral medications for herpes in pregnancy [20].

First episode Recurrent episodes

Recommended daily Length of Recommended daily Length of
Pregnancy Antiviral drug Antiviral drug
dosage therapy dosage therapy
Episodic Acyclovir Orally: 5 × 200 mg 10 days Acyclovir Orally: 5 × 200 mg 5 days
treatment Valacyclovir Orally: 2 × 500 mg 10 days Valacyclovir Orally: 2 × 500 mg 5 days
Suppressive Acyclovir Orally: 3 × 400 mg Acyclovir Orally: 3 × 400 mg
treatment From week 36 From week 36
Valacyclovir Orally: 2 × 250 mg Valacyclovir Orally: 2 × 250 mg
until delivery until delivery

which are then able to pass the placenta and reach the fetus. It 8. Conclusions
is so unusual that the fetus develops the infection with HSV.
If the lesion is present in genital skin during delivery, the risk Genital herpes is a preventable chronic disease. Although
of infection for the baby will be 2–5% [28]. most HSV infections are subclinical, clinical disease can be
Instead, a woman with periodic reactivations of the virus associated with substantial physical and psychosocial mor-
and asymptomatic at birth has a low risk (1%) to eliminate bidity. The clinical manifestations are diverse; hence a sus-
the virus with vaginal secretions, so the risk of fetal infection pected diagnosis of HSV should be confirmed by laboratory
is even lower (0.02–0.05%) [28]. tests. The management of genital herpes should be tailored
Randomized trials showed that the use of antiviral to the individual and should include counselling about the
drugs from the 36th week of pregnancy reduces the risk variable natural history appearance of lesions, education
of spreading of the virus in the absence of clinically visible about prevention of transmission, the link between HSV and
lesions and the risk of viral reactivation with decreased HIV, and discussion to assess the psychosexual effects of
percentage of caesarean sections [21]. the disease. Antiviral therapy is safe and effective, both for
The use of antiviral drugs is allowed before the 36th week episodic treatment and chronic suppression of HSV.
in case of very serious events in the mother, or if there is an A large amount of information on the transmission of
increased risk of preterm delivery. herpes from male to pregnant partner, on the mode of trans-
The therapy includes the administration of acyclovir mission from mother to newborn, mainly by maternal first-
400 mg tablets 3 times daily or acyclovir 200 mg tablets 4 time infection in the third trimester of pregnancy, has been
times a day from week 36 until delivery, and viral cultures on published in literature.
cervical-vaginal secretions from 36th week of gestation are Since the increasing prevalence of genital HSV infection
required. Recent studies also suggest the use of valacyclovir and apparent increase in the incidence of neonatal herpes,
at a dose of 200 mg 2 times a day. we have focused our attention on prevention of maternal
In absence of clinical herpes lesions but with positive viral foetal transmission as well as on the management of infected
cultures at delivery, caesarean section is recommended. On pregnant women and neonate. Further studies are needed
the contrary, if all viral cultures are negative, in the absence to monitor the changing HSV-1 and HSV-2 trends and to
of clinical lesions, a spontaneous delivery is indicated. develop effective strategies to prevent HSV infection. Finally,
Finally, in presence of clinical genital HSV lesions at the the major vaccine strategies under development should take
onset of delivery, if it may be assumed that the foetal lungs are in to account the three important features of herpesviruses:
mature, a caesarean section should be performed as quickly the viral latency, the herpes immune escape, and the high
as possible within 4–6 hours after membranes rupture [20, seroprevalence.
21, 34].

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