Herpes simplex virus infection in pregnancy and Neonate
Widodo Judarwanto. Children Allergy Online Clinic, Jakarta Indonesia
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Herpes simplex virus (HSV) infection is one of the most common viral sexually transmitted diseases worldwide. The first time infection of the mother may lead to severe illness in pregnancy and may be associated with virus transmission from mother to foetus/newborn. Since the incidence of this sexually transmitted infection continues to rise and because the greatest incidence of herpes simplex virus infections occur in women of reproductive age, the risk of maternal transmission of the virus to the foetus or neonate has become a major health concern. The medical literature and pertinent publications to define the status of art regarding the epidemiology, the diagnosis, the therapy and the prevention of HSV in pregnant women and neonate. Special emphasis is placed upon the importance of genital herpes simplex virus infection in pregnancy and on the its prevention to avoid neonatal HSV 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.
Herpes simplex virus transmission to pregnancy
Genital herpes simplex virus (HSV) infection is one of the most common viral sexually transmitted infections. The majority of women with genital herpes will have a recurrence during pregnancy. Transmission of the virus from mother to fetus typically occurs by direct contact with virus in the genital tract during birth
New findings reveal that first-time infection of the mother is the most important factor for the transmission of genital herpes from mother to fetus/newborn. Interventions based on these findings will lead to new management of the pregnant patient with genital herpes prior to pregnancy and measures to prevent the acquisition of herpes during pregnancy.
Risk factors for the transmission of herpes from mother to newborn have been detailed. It is the pregnant woman who acquires genital herpes as a primary infection in the latter half of pregnancy, rather than prior to pregnancy, who is at greatest risk of transmitting this virus to her newborn. This is true for both herpes simplex virus type-1 and herpes simplex virus type-2. Additional risk factors for neonatal herpes simplex virus infection include the use of a fetal-scalp electrode and maternal age of less than 21 years.
Risk factors for the transmission of herpes from mother to newborn are detailed. Antiviral suppressive therapy initiated in the late third trimester has been shown to decrease viral shedding and the need for cesarean section.
Randomized controlled trials which assessed the effectiveness of antivirals compared to placebo or no therapy, on neonatal herpes and maternal disease endpoints among pregnant women with genital herpes. Seven randomized controlled trials (1249 participants) which met our inclusion criteria compared acyclovir to placebo or no treatment (five trials) and valacyclovir to placebo (two trials). The effect of antepartum antiviral prophylaxis on neonatal herpes could not be estimated. There were no cases of symptomatic neonatal herpes in the included studies in either the treatment or placebo groups. Women who received antiviral prophylaxis were significantly less likely to have a recurrence of genital herpes at delivery (relative risk (RR) 0.28, 95% confidence interval. Women who received antiviral prophylaxis were also significantly less likely to have a cesarean delivery for genital herpes. Women who received antiviral prophylaxis were significantly less likely to have HSV detected at delivery.
AUTHORS’ CONCLUSIONS: Women with recurrent genital herpes simplex virus should be informed that the risk of neonatal herpes is low. There is insufficient evidence to determine if antiviral prophylaxis reduces the incidence of neonatal herpes. Antenatal antiviral prophylaxis reduces viral shedding and recurrences at delivery and reduces the need for cesarean delivery for genital herpes. Limited information exists regarding the neonatal safety of prophylaxis. The risks, benefits, and alternatives to antenatal prophylaxis should be discussed with women who have a history and prophylaxis initiated for women who desire intervention.
Herpes simplex virus transmission to the neonate
Herpes simplex viruses (HSV) are ubiquitous pathogens which can be transmitted vertically causing significant morbidity and mortality in neonates. Neonatal HSV infection is infrequent with an incidence ranging from 1 in 3,500 to 1 in 20,000, depending on the population. Neonatal HSV infection is much more frequent in infants born to mothers experiencing a primary HSV infection with an incidence approaching 50%, while infants born to mothers experiencing recurrent HSV infection have an incidence of less than 3%.
Neonatal herpes simplex virus (HSV) infection can have severe consequences. Skin, eye and mouth infection is rarely fatal, but disseminated or central nervous system (CNS) disease has a mortality rate of 80% in the absence of therapy, and most surviving infants have neurological sequelae. Aciclovir therapy can improve the outcome of neonatal herpes, but is often delayed due to the early non-specific symptoms of the disease. Even with early therapy, some infants develop disseminated infection or CNS complications. The virus is usually vertically transmitted to the neonate from an infected mother during delivery. As such, the optimal strategy for reducing the morbidity of neonatal herpes is to prevent the neonate from acquiring HSV infection at delivery.
The highest risk of neonatal infection occurs when the mother sheds HSV at labour, which happens more frequently in women who acquire genital herpes in the third trimester. Therefore, one approach for reducing maternal-fetal transmissions is to prevent HSV acquisition in late pregnancy. Definitive classification of genital HSV infection during pregnancy as either primary, non-primary first episode or recurrent can be accomplished only when clinical evaluation is accompanied by laboratory testing, including the use of gG-specific serological tests. The serological status of the mother’s sexual partner should be considered when determining her risk of infection.
Neonatal infections are clinically categorised according to the extent of the disease. They are: (i) skin, eye and mouth (SEM) infections; (ii) central nervous system infection (encephalitis)–neonatal encephalitis can include SEM infections; and (iii) disseminated infection involving several organs, including the liver, lung, skin and/or adrenals. The central nervous system may also be involved in disseminated infections. Caesarean section, where the amniotic membranes are intact or have been ruptured for less than 4 hours, is recommended for those women who have clinical evidence of active herpes lesions on the cervix or vulva at the time of labour. This procedure significantly decreases the risk of transmission to the infant. Diagnosis of neonatal infection requires a very high level of clinical awareness as only a minority of mothers will have a history of genital HSV infection even though they are infected. Careful physical examination and appropriate investigations of the infant should accurately identify the infection in the majority of cases.
In spite of the availability of antiviral therapy for the treatment of neonatal herpes simplex virus infections, the outcome remains poor, particularly for babies with disseminated multi-organ infection or central nervous system disease. This review considers recent advances that impact on disease management.
Two areas of investigation have impacted on our understanding of neonatal herpes simplex virus infection. First, the transmission of infection from mother to baby has been clarified by extensive epidemiological investigations of genital herpes in pregnant women at term. Risk factors for neonatal herpes simplex virus disease include first-episode maternal infection in the third trimester, invasive monitoring, delivery before 38 weeks, and maternal age of less than 21 years.
Recent findings from epidemiological studies have identified women at risk of delivering a child who develops neonatal herpes simplex virus infection, and suggest methods to decrease maternal-fetal transmission. If infection is identified in the pregnant woman, cesarean delivery decreases the frequency of neonatal disease. With neonatal disease, acyclovir should be administered promptly at higher dosages and for longer periods than previously reported.
Regarding the management of neonatal herpes simplex virus disease, the utilization of high-dose acyclovir (20 mg/kg every 8 h) for 21 days significantly reduces mortality for babies with either encephalitis or disseminated disease.
Treatment is recommended where diagnosis is confirmed or there is a high level of suspicion. The current recommendation for treatment is aciclovir 20 mg/kg 3 times daily by intravenous infusion. Careful monitoring of hydration and renal function as well as meticulous supportive care of a very sick infant is also required. The newer anti-herpes agents, valaciclovir and famciclovir, offer no advantage over aciclovir and are not recommended for neonatal HSV infection.
Prognosis is dependent upon the extent of disease and the efficacy of treatment, with highest rates of morbidity and mortality in disseminated infections, followed by central nervous system infection and the least in SEM infection. However, SEM infection is associated with poor developmental outcome even in infants who do not have encephalitis. Studies to improve the outcome of SEM infection are in progress. Neonatal HSV infections, although being relatively uncommon, are associated with significant morbidity and mortality if unrecognised and specific treatment is delayed. Diagnosis relies on a high level of clinical suspicion and appropriate investigation. With early therapy, the prognosis for this infection is considerably improved.
The use of weekly viral cultures in pregnant women with confirmed genital herpes is not warranted, as they do not predict an infant’s risk of acquisition of HSV at delivery and are not cost-effective. High-risk susceptible women should be counselled about abstinence and reducing oral-genital contact near term. Observational studies suggest that caesarean section can reduce transmission of neonatal herpes, and is warranted for women who shed HSV at delivery, although different countries vary in their approach to caesarean sections and so universal recommendations are not available. If maternal antiviral therapy is considered, the potential benefits of treatment should be balanced against potential adverse outcomes for mother and fetus, although it may be warranted when the mother has severe or life-threatening disease. Studies on the use of antiviral prophylaxis in women with known recurrences at labour are ongoing. Invasive fetal monitoring can increase the risk of neonatal herpes, and should only be used in HSV-2 seropositive women for defined obstetrical indications.
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