INTRODUCTION — Herpes simplex virus (HSV) infection is prevalent worldwide among women of childbearing age. During pregnancy, transmission from mother to fetus is a concern, as neonatal infection can result in serious morbidity and mortality.
The major issues related to genital herpes infection in pregnancy will be reviewed here. The epidemiology, clinical manifestations, diagnosis, treatment, and prevention of primary and recurrent genital HSV infection in the general population, and issues related to management of the infected neonate, are discussed separately:
CLASSIFICATION OF GENITAL HSV INFECTIONS — The three clinical classifications of genital herpes simplex virus (HSV) infection are (table 1):
●Primary – Patient has a first occurrence of a genital HSV lesion and no pre-existing herpes simplex virus type 1 (HSV-1) or herpes simplex virus type 2 (HSV-2) antibodies.
●Nonprimary first-episode – Patient has a first occurrence of a genital HSV lesion, but has pre-existing HSV antibodies that are different from the HSV type recovered from the genital lesion. For example:
•HSV-2 is recovered from the genital lesion of a patient with pre-existing HSV-1 antibodies and no HSV-2 antibodies. This is the most common scenario, particularly in patients with a history of orolabial herpes.
•HSV-1 is recovered from the genital lesion of a patient with pre-existing HSV-2 antibodies and no HSV-1 antibodies. This scenario is rare.
●Recurrent – The HSV type recovered from the genital lesion is the same type as pre-existing antibodies in the serum. For patients with previously asymptomatic genital infection, a recurrence may be the first-recognized episode of genital herpes.
Both type-specific serologic and virologic assays are usually required for accurate classification , except in the case of well-documented recurrent HSV previously confirmed by culture or polymerase chain reaction (PCR) . Type-specific antibodies to HSV generally develop within the first 12 weeks after infection and persist indefinitely.
Accurate classification is particularly important during pregnancy because a newly acquired genital infection (primary or nonprimary first-episode) near the time of delivery is a major risk factor for transmission to the neonate. The risk of neonatal transmission at delivery is much lower in patients with recurrent genital infection [2,3]. (See 'Vertical transmission' below.)
SEROPREVALENCE — A prior herpes simplex virus (HSV) infection with either herpes simplex virus type 1 (HSV-1) or herpes simplex virus type 2 (HSV-2) is common among pregnant women . A study using data from the 2007 to 2014 United States National Health and Nutrition Examination Survey (NHANES) estimated that the seroprevalence of HSV-1 and HSV-2 in pregnant women was 59.3 and 21.1 percent, respectively . Compared with the prior seven-year period, there was a nonsignificant increase in seronegativity among pregnant women consistent with the decline in the overall prevalence of HSV-1 and HSV-2 in the United States . While this means that a larger fraction of reproductive-age women may be seronegative, and thus at risk for acquiring HSV-1 or HSV-2 during pregnancy, the prevalence of these infections is also likely to be lower among their partners.
Concurrently, others have reported that the prevalence of neonatal HSV infection has remained stable [7,8]. Although HSV-2 caused the majority of virologically confirmed genital HSV infections in the past, HSV-1 has been associated with an increasing proportion of cases, especially among young women. This may explain why the rate of neonatal HSV infection has not decreased along with the decrease in maternal HSV-2 prevalence. (See "Epidemiology, clinical manifestations, and diagnosis of genital herpes simplex virus infection", section on 'Epidemiology'.)
CLINICAL MANIFESTATIONS — The clinical manifestations of genital herpes simplex virus (HSV) can vary widely depending upon whether the infection is primary, nonprimary first episode, or recurrent. Clinical findings are similar in pregnant and nonpregnant women, and are discussed in detail separately. (See "Epidemiology, clinical manifestations, and diagnosis of genital herpes simplex virus infection", section on 'Primary infection' and "Epidemiology, clinical manifestations, and diagnosis of genital herpes simplex virus infection", section on 'Nonprimary infection' and "Epidemiology, clinical manifestations, and diagnosis of genital herpes simplex virus infection", section on 'Recurrent infection'.)
Briefly, the initial presentation of primary genital infection can be severe, with painful genital ulcers, pruritus, dysuria, fever, tender inguinal lymphadenopathy, and headache. However, most patients have only mild symptoms or remain asymptomatic. In a prospective study of pregnant women who were initially HSV seronegative, only one-third of those who seroconverted had symptoms consistent with genital HSV infection .
The initial presentation of nonprimary first-episode genital infection tends to be milder than in primary infection, but the classification cannot be established on clinical grounds and requires both virologic and serologic tests.
Recurrent infections may be preceded by prodromal symptoms, such as pruritus, burning, or pain, before lesions are visible. Recurrent infections tend to have mild localized symptoms with few lesions and lack systemic findings. The lesions may be nontender or atypical in appearance (eg, fissure, vulvar irritation). The duration of lesions and viral shedding are shorter than during a primary episode.
DIAGNOSIS — The clinical diagnosis of genital herpes simplex virus (HSV) infection is generally made by the finding of vesicular or ulcerated lesions (picture 1A-B) but should be always confirmed with laboratory testing. Diagnostic tests for HSV infection include polymerase chain reaction (PCR), viral culture, direct fluorescent antibody testing, and type-specific serologic tests. The approach to diagnosis of genital HSV during pregnancy depends on the clinical presentation:
●For women without a history of genital HSV who present with an active genital ulcer during pregnancy, we perform a direct viral test on the lesion and type-specific serologic testing. The vesicle can be unroofed and a swab of the vesicular fluid and ulcer base sent for PCR. PCR is more sensitive than culture and has become the preferred test for diagnostic testing in symptomatic patients [10-13]. Diagnostic techniques for HSV testing are discussed in detail elsewhere. (See "Epidemiology, clinical manifestations, and diagnosis of genital herpes simplex virus infection", section on 'Diagnosis'.)
Genital HSV infection is diagnosed by a positive viral test. Type-specific HSV serology at the time of initial presentation is necessary for classifying maternal infection as primary, nonprimary, or recurrent (table 1) . (See 'Classification of genital HSV infections' above.)
For women with genital ulcers and a high clinical suspicion for HSV infection but negative tests for virus detection and for antibody, we repeat serologic testing three to four weeks later. If this repeat testing demonstrates seroconversion of either type-specific antibody, the diagnosis of primary infection (or nonprimary first-episode, if the other type-specific antibody was positive at baseline) can be made. If there is no seroconversion, the genital ulcers are unlikely to represent HSV infection.
●Women who have a history of laboratory confirmed genital HSV do not warrant further testing. However, if a woman with a history of genital ulcers without prior laboratory diagnosis presents with an active genital ulcer during pregnancy, we perform a viral test on the lesion to confirm the recurrent HSV diagnosis. PCR is especially advantageous in the setting of a recurrent episode, as it has greater sensitivity in recurrent infection than viral culture. However, if the clinical history is suggestive of HSV infection, a negative viral test does not rule out the diagnosis of HSV infection. If a definitive diagnosis is desired in this situation, serology can be performed to confirm HSV infection.
We do not perform rapid HSV PCR testing to identify women with asymptomatic genital shedding at the time of delivery. It is unclear whether using this information to decide upon the route of delivery can reduce the risk of neonatal HSV infection.
Diagnostic testing is discussed in detail elsewhere. (See "Epidemiology, clinical manifestations, and diagnosis of genital herpes simplex virus infection", section on 'Diagnosis'.)
General principles — Transmission of herpes simplex virus (HSV) to the neonate usually occurs during labor and delivery as a result of direct contact with virus shed from infected sites (cervix, vagina, vulva, perianal area).
The key principles for understanding vertical transmission of HSV infection are :
●Most mothers of newborns with perinatally-acquired HSV infection lack a history of clinically evident genital herpes .
●The highest risk for neonatal infection occurs in women with a primary genital HSV infection acquired near the time of delivery. The risk of neonatal infection is slightly lower in women with nonprimary first-episode genital infection, and substantially reduced in women with recurrent HSV. In two case series of women cultured on admission to labor and delivery and subsequently found to have positive culture results, the frequency of neonatal infection was [2,3]:
The observation that newborns of mothers with a primary or nonprimary first-episode genital infection near the time of labor are at the highest risk for infection is likely related to both the absence of maternal type-specific anti-HSV antibodies and to greater viral exposure (viral load and duration of viral shedding) during primary and nonprimary first-episode genital infection .
Women with a primary infection or nonprimary first-episode genital infection early in pregnancy who develop type-specific HSV antibodies before the onset of labor appear to be at a similar low risk of neonatal transmission as women with recurrent infection . As discussed above, type-specific antibodies to HSV generally develop within the first 12 weeks after infection and persist indefinitely. (See 'Classification of genital HSV infections' above.)
●Viral shedding can occur in the absence of maternal symptoms and lesions [13,15,18,19]. As an example, in a study of nonpregnant individuals with antibodies to herpes simplex virus type 2 (HSV-2), rates of subclinical viral shedding, as measured by daily HSV polymerase chain reaction (PCR) testing on genital swabs, were 13 and 9 percent among individuals with a history of symptomatic and asymptomatic infection, respectively . These concepts are discussed in detail elsewhere. (See "Epidemiology, clinical manifestations, and diagnosis of genital herpes simplex virus infection".)
●The frequency of viral shedding is higher in genital HSV-2 versus genital herpes simplex virus type 1 (HSV-1) infection. Clinical management of the pregnancy is not influenced by HSV type, although the type of genital HSV (HSV-1 versus HSV-2) affects the risk of neonatal transmission and neonatal sequelae. Both HSV-1 and HSV-2 may cause localized skin, eye, and mouth; CNS; or disseminated disease; however, HSV-1 has been associated more often with cutaneous skin involvement, and HSV-2 has been associated more often with CNS disease and with a poorer outcome.
●In utero infection acquired transplacentally or transcervically (across the amniochorionic membranes) has been reported in women with primary HSV infection, and could result in miscarriage, congenital anomalies (eg, ventriculomegaly and other CNS abnormalities), preterm birth, and/or intrauterine growth restriction [9,20-23]. Recurrent HSV has not been associated with these outcomes . In utero acquisition of infection should be considered in cases of early neonatal HSV infection despite prelabor cesarean delivery and intact fetal membranes [2,25]. (See "Neonatal herpes simplex virus infection: Clinical features and diagnosis", section on 'Intrauterine HSV'.)
●Use of invasive fetal monitoring and preterm birth increase the risk of neonatal infection in patients with viral shedding .
Evidence — Estimates of the risk and risk factors for vertical transmission were derived, in part, by the following seminal studies:
In a prospective study between 1982 and 1999, 58,000 pregnant women in Washington state were classified as having primary, nonprimary, or reactivation HSV by comprehensive testing with serologic, culture, and PCR techniques . HSV was isolated from the cervix and external genitalia in 202 (0.5 percent) women at the time of labor. The following observations were made in relation to neonatal infection:
●Viral genital shedding in labor was a strong predictor of neonatal HSV infection (OR 346). Neonatal HSV infection occurred in 5 percent (10/202) of women with a positive HSV culture versus 0.02 percent (6/39,821) of women with a negative culture.
●The highest risk of neonatal HSV infection was in neonates of women with newly acquired primary genital HSV (ie, HSV-seronegative): 54 per 100,000 live births compared with 26 per 100,000 live births when the mother was HSV-1-seropositive and 22 per 100,000 live births when the mother was HSV-2-seropositive.
●Other significant risk factors for neonatal HSV included HSV isolation from the cervix (OR 33), shedding HSV-1 rather than HSV-2 (OR 17), invasive fetal monitoring (OR 7), delivery before 38 weeks (OR 4), and maternal age <21 years (OR 4). Delivery by cesarean was protective (OR 0.14).
In a study of 7046 HSV-seronegative pregnant women followed throughout pregnancy, 94 developed primary infections . The time of acquisition of HSV infection was known for 60 of these pregnancies: 30 percent occurred in the first trimester, 30 percent in the second trimester, and 40 percent in the third trimester.
●Neonatal HSV infection occurred in 44 percent (4/9) of infants born to women who acquired genital HSV infection shortly before labor (one of these infants died).
●Seven of the nine women with genital HSV infection shortly before labor had antibody to HSV-1 and were culture-positive for HSV-2 during labor (ie, nonprimary first-episode genital infection); two newborns of these seven women developed neonatal HSV.
●Two women were HSV-seronegative, but were HSV-1 culture-positive (primary infection) at delivery. Both transmitted HSV-1 to their neonates.
●Seroconversion completed before labor was not associated with perinatal morbidity or any cases of neonatal HSV infection.
PREGNANCY MANAGEMENT — Management strategies for women who have genital herpes during pregnancy include suppressive antiviral therapy starting at 36 weeks to reduce the risk of recurrence at labor, and cesarean delivery for select women to reduce the risk of neonatal transmission. However, neither intervention fully eliminates the risk of neonatal herpes infection. Our approach to antiviral therapy for pregnant women with herpes simplex virus (HSV) considers the classification of infection (ie, primary genital, nonprimary first genital episode, recurrent), severity of symptoms, and the timing of infection relative to delivery. This approach is consistent with that of the American College of Obstetricians and Gynecologists (ACOG) .
Use of antiviral therapy
Treatment of primary or nonprimary first-episode genital infection — For women without a history of genital HSV infection who present with a new genital ulcer during pregnancy, we recommend empiric antiviral therapy while awaiting viral studies. Although newly acquired genital HSV is self-limited, treatment can reduce the duration and severity of symptoms and the duration of viral shedding. We use acyclovir therapy (400 mg orally three times daily for 7 to 10 days ; treatment can be extended if healing is incomplete after 10 days). Initial intravenous (IV) acyclovir (5 to 10 mg/kg body weight IV every 8 hours) is indicated for complicated infection (central nervous system disease, end-organ disease, disseminated HSV) . Acetaminophen and sitz baths help to relieve fever, vulvar pain, dysuria, and other local symptoms. (See 'Drug choice, dose, and safety' below and "Treatment of genital herpes simplex virus infection", section on 'Consideration in complicated infection'.)
Subsequently, antiviral therapy is restarted at 36 weeks for suppression. (See 'Suppressive therapy at 36 weeks' below.)
However, for women who have a primary or nonprimary first-episode lesion during the third trimester, we discuss the possibility of continuing antiviral therapy without interruption from the time of treatment initiation through delivery. Although there are no data to support a strong recommendation for this approach, the rationale is that any woman may give birth before 36 weeks because of preterm labor/prelabor rupture of membranes, first-episode HSV infection may result in prolonged viral shedding, and preterm labor and rupture of membranes are associated with a relatively high risk of HSV transmission. Although we suggest cesarean delivery for women with a primary or nonprimary first-episode genital infection acquired during the latter weeks of pregnancy, this is a shared decision. Continuing antiviral therapy may be particularly attractive to women who prioritize having a vaginal delivery, since antiviral therapy reduces the risk of lesions at the time of delivery. (See 'Route of delivery' below.)
Treatment of recurrent infection — Most recurrent episodes are short and do not require intervention. Thus, many pregnant women and their clinicians choose not to treat recurrences with episodic antiviral therapy or use suppressive antiviral therapy during the first 35 weeks of pregnancy in order to limit unnecessary exposure to antiviral medication. However, some women may desire treatment because of severe symptoms or frequent recurrences (table 2).
Suppressive therapy at 36 weeks — For all women who present with a genital HSV lesion anytime during pregnancy, whether with a primary, nonprimary first-episode, or recurrent infection, we recommend initiating suppressive therapy at 36 weeks of gestation to continue until the onset of labor. We use acyclovir 400 mg three times daily as suppressive therapy. Doses for suppressive therapy are higher in pregnant compared with nonpregnant women because of increased renal clearance during pregnancy. (See 'Drug choice, dose, and safety' below.)
Suppressive therapy from 36 weeks of gestation until the onset of labor reduces the frequency of symptomatic HSV recurrence at the onset of labor, and thus reduces the need for cesarean delivery (see 'Route of delivery' below). It also reduces viral shedding, which is important since viral shedding may result in vertical transmission. Women with one or more symptomatic genital HSV recurrences during pregnancy are most likely to benefit . There is no evidence that HSV seropositive women without active genital lesions during pregnancy benefit from suppressive therapy, and we do not offer it to such women.
In a 2008 meta-analysis of seven randomized trials involving 1249 pregnant women in the third trimester who had been diagnosed with genital herpes infection before or during pregnancy and began acyclovir or placebo prophylaxis at 36 weeks of gestation, acyclovir significantly reduced the risk for :
●Clinical HSV recurrence at the time of delivery (RR 0.28, 95% CI 0.18-0.43)
●Cesarean delivery for clinically recurrent genital herpes (RR 0.30, 95% CI 0.20-0.45)
●Asymptomatic viral shedding at delivery (OR 0.14, 95% CI 0.05-0.39)
Although suppressive therapy markedly reduces the frequency of both symptomatic disease and asymptomatic viral shedding, only minimal data are available assessing its impact on the incidence of neonatal herpes . Suppressive therapy does not completely eliminate viral shedding. A multicenter case series described eight cases of herpes in neonates of women prescribed treatment/suppressive therapy during pregnancy; five of the women were on suppressive therapy on the day of delivery . Among the five women on therapy at delivery, two neonates were delivered by cesarean 0 and 27 hours after rupture of membranes, respectively, and three neonates were delivered vaginally 45 minutes, 12 hours, and 19 days after membrane rupture, respectively. No woman had visible genital lesions at delivery. Of note, some of the mothers did not take all of their medication as prescribed.
Drug choice, dose, and safety — Antiviral drug dosing is shown in the table (table 2).
Of the available anti-HSV medications (acyclovir, famciclovir, valacyclovir), the greatest clinical experience during pregnancy has been with acyclovir, dosed at 400 mg orally three times daily. For acute episodes, it is given for 7 to 10 days, or longer if lesions have not yet healed; for suppressive therapy, it is given from 36 weeks of gestation until delivery.
Valacyclovir is an alternative for both acute and suppressive therapy, although it is usually a more expensive option (including generic valacyclovir) with fewer safety and efficacy data . However, if patient adherence is a concern, valacyclovir may be preferable since twice-daily dosing is more convenient.
Both animal and human data on acyclovir exposure during pregnancy, including the first trimester, suggest that this drug is safe at all stages of pregnancy . Data are more limited but reassuring regarding the use of valacyclovir. There are minimal human data on famciclovir exposure in pregnancy and we generally avoid this agent when possible as there are more robust data with acyclovir and valacyclovir and these agents are readily available.
Weekly or serial genital culture or polymerase chain reaction (PCR) testing for HSV during late gestation is not recommended [26,27], as these do not predict shedding at the time of delivery . Maternal HSV is not an indication for antepartum fetal monitoring (nonstress test, biophysical profile) since the fetus and placenta are typically not infected.
Antepartum obstetric procedures — Transcervical procedures (eg, cerclage, chorionic villus sampling) should be avoided in women with genital lesions to reduce the risk of infecting the placenta or membranes but may be performed in asymptomatic patients. Transabdominal procedures (eg, amniocentesis, fetal blood sampling) are not contraindicated in women with active genital disease .
Route of delivery — We ask all women with a history of HSV about prodromal symptoms and examine them for external lesions when they present for evaluation on the labor and delivery unit.
We agree with recommendations from the Centers for Disease Control and Prevention (CDC) and ACOG to offer cesarean delivery as soon as possible after the onset of labor/rupture of membranes to women with a history of genital HSV and either of the following [26,27]:
●Active genital lesions (including those that have crusted)
●Prodromal symptoms (genital pain or burning) that may be associated viral shedding
If the membranes have been ruptured for longer than six hours, we still offer cesarean delivery, but discuss the lack of data about benefit . No studies have established an interval after rupture of membranes when cesarean delivery clearly has no neonatal benefit.
For women with no active lesions or prodromal symptoms, decisions on route of delivery depend on the type and timing of the HSV infection:
●For women with no active lesions or prodromal symptoms but a primary or nonprimary first-episode genital infection during the current pregnancy, the optimal approach to route of delivery is unclear because viral shedding can be prolonged in this setting and maternal antibodies may not have developed before delivery (see 'Vertical transmission' above). In the absence of obstetric indications for cesarean delivery, the decision depends heavily on the woman's preferences and values. For all such women, we discuss the uncertainty of the magnitude of the transmission risk, particularly as the duration of time between the infection and delivery increases, and the evidence that cesarean delivery decreases but does not completely eliminate that risk. For those women whose primary or nonprimary first-episode genital infection occurred during the latter weeks of pregnancy, we suggest cesarean delivery given the possibility of a high risk of neonatal transmission . Nevertheless, women who wish to avoid cesarean may reasonably decline in the absence of prodromal syndromes or HSV lesions. Conversely, women whose genital infection occurred earlier during pregnancy may reasonably opt for cesarean to try to mitigate any possible risk of neonatal transmission.
Expert groups have noted the potential value of cesarean when a primary or nonprimary first-genital herpes infection occurs in the latter weeks of pregnancy. As an example, the Royal College of Obstetricians recommends cesarean delivery for women who present with a first-episode genital herpes infection in the third trimester, particularly those who develop symptoms within six weeks of expected delivery . The American College of Obstetricians and Gynecologists guidelines state that women with a primary or nonprimary first-episode genital HSV infection during the third trimester of pregnancy may be offered cesarean delivery given the possibility of prolonged asymptomatic viral shedding .
●For women with a history of recurrent HSV but no active lesions or prodromal symptoms, the risk for neonatal HSV is too low (estimated to be 2/10,000) to warrant cesarean delivery .
Similarly, we do not perform cesarean delivery in women with active nongenital HSV lesions (eg, back, buttock, thigh); although the risk of genital shedding is higher than in asymptomatic women, the risk of neonatal transmission is still likely not high enough to warrant cesarean, and the nongenital lesions do not confer a measurable risk of transmission in the absence of direct contact . These lesions should be covered with an occlusive dressing during labor and delivery.
The protective effect of cesarean delivery against fetal transmission of HSV is supported by a prospective study of over 58,000 pregnant women in Washington state between 1982 and 1999 . Among the 202 women who had HSV isolated from the cervix or external genitalia at the time of labor, 10 (5 percent) had neonates who developed HSV infection. Women with positive HSV cultures who delivered by cesarean had a marked reduction in the frequency of infected neonates compared with those who delivered vaginally (1/85 versus 9/117 [1.2 versus 7.7 percent], odds ratio 0.14, 95% CI 0.02-1.08). However, as noted in this and other studies, delivery by cesarean does not prevent all neonatal infections [2,21,25]. In a national surveillance study from the CDC of 184 cases of neonatal HSV infection, 15 occurred despite cesarean delivery performed prior to membrane rupture .
Labor management — Use of a fetal scalp electrode, which causes a break in the fetal skin, is a potential risk factor for acquisition of neonatal HSV in women with asymptomatic viral shedding. Therefore, it is prudent to limit the use of fetal scalp electrodes among laboring women with a history of HSV infection. External fetal heart rate monitoring is preferred as long as adequate information can be obtained.
Avoidance of other procedures, such as vacuum or forceps delivery, is also prudent if possible since these devices can cause fetal skin abrasions and increase the risk for HSV infection if asymptomatic viral shedding is present.
Preterm premature rupture of membranes — Clinical decision-making for patients with preterm premature rupture of membranes (PPROM) and active herpes simplex virus (HSV) infection balances the risks associated with preterm birth against the risk for ascending in utero infection. The consequences of prematurity depend upon the week of gestation; the risk for in utero infection depends upon whether the woman's clinical episode is primary, first episode genital, or recurrent.
These issues are discussed below. The overall management of PPROM is reviewed separately. (See "Preterm prelabor rupture of membranes: Clinical manifestations and diagnosis".)
Recurrent HSV infection and PPROM — Limited evidence supports expectant management for PPROM in the second trimester in women with active recurrent genital herpes. In the third trimester, the risk associated with prematurity (which varies by gestational age) must be balanced with the risk for in utero infection on a case-by-case basis. If delay of delivery is appropriate because of concerns about gestational age remote from term, we suggest administering intravenous acyclovir (5 mg/kg every 8 hours) to shorten the duration of active lesions in the mother and to decrease viral burden. However, the ability of acyclovir to prevent maternal-fetal transmission has not been proven. A course of antenatal corticosteroids is also administered to pregnancies <34 weeks to reduce the morbidity and mortality related to preterm birth. (See "Antenatal corticosteroid therapy for reduction of neonatal respiratory morbidity and mortality from preterm delivery".)
An observational study examined neonatal outcomes in 29 pregnancies complicated by both PPROM (at 25 to 31 weeks of gestation) and recurrent HSV infection, and managed expectantly . Expectant management consisted of hospitalization and frequent vital sign monitoring; only two women received oral acyclovir for clinical symptoms. The mean gestational age at herpes lesion development after PPROM was 28.7 weeks (range 24.6 to 31.0 weeks). The mean interval from recognition of infection to delivery was 13.2 days (range 1 to 35 days). The control group consisted of patients with PPROM without concomitant HSV infection. Major findings were:
●No neonatal HSV infections occurred.
●No neonatal HSV cultures were positive.
●Twelve infants (41 percent) had major morbidity related to prematurity and three died. Morbidity was similar in cases (PPROM with recurrent HSV) and controls (PPROM without HSV).
Based upon these data, the authors calculated that the maximum risk for development of a neonatal HSV infection in the setting of PPROM and recurrent genital HSV infection was 10 percent. This risk was close to the neonatal mortality rate at 26 to 27 weeks and was significantly lower than the risk for major morbidity caused by prematurity .
Primary or first-episode genital HSV infection and PPROM — No data are available on the risk of fetal infection during expectant management of primary or nonprimary first-episode genital HSV infection complicated by PPROM. Optimal management remains uncertain. Confirmation of the diagnosis of primary or nonprimary first-episode genital infection is desirable. (See 'Diagnosis' above.)
Given the absence of data to inform decision-making, it is difficult to weigh the risks of in utero infection against the risks associated with preterm delivery, which vary significantly by the week of gestation. In light of the high risk for fetal transmission during primary infection  and the high risk for neonatal morbidity/mortality in infected fetuses, some authors suggest prompt cesarean delivery of pregnancies ≥28 weeks of gestation in an attempt to minimize the risk for fetal infection; others use a threshold of ≥32 weeks. The neonate is then treated with acyclovir and surfactant.
Before 28 (or 32) weeks, the risks associated with prematurity are high  and may outweigh the risk for fetal infection with expectant management, so acyclovir is administered to the mother to shorten the duration of lesions and reduce viral shedding; there are no data showing prevention of neonatal infection.
POSTPARTUM AND NEONATAL MANAGEMENT
●Parents and other caretakers with active lesions, regardless of site, should be careful when handling the infant: lesions should be covered and hands should be washed before touching the baby. Five to 15 percent of neonatal herpes is acquired after birth from a family member .
●Communication with the pediatrician about possible neonatal herpes simplex virus (HSV) exposure is essential. Neonates with possible perinatal exposure to HSV should be monitored for clinical evidence of HSV infection. (See "Neonatal herpes simplex virus infection: Management and prevention".)
SCREENING PREGNANT WOMEN WITH NO HSV HISTORY — Serologic screening has been proposed to (1) identify women without herpes simplex virus (HSV) so they can take precautions to avoid acquiring an HSV infection and (2) identify women with a past history of HSV so they can be offered suppressive antiviral therapy, examined carefully for lesions at the onset of labor, and offered cesarean delivery, if indicated. We agree with expert panels that recommend against universal screening [2,26,41,42]; this is due in part to the lack of commercially available accurate antibody tests. Available evidence indicates that screening for HSV would not meet usual criteria for an effective preventive strategy [43-45], as has been demonstrated in other infections, such as human immunodeficiency virus (HIV) and hepatitis B virus (HBV) .
Some couples may choose to be screened. If testing is performed, type-specific glycoprotein G (gG)-based assays for HSV antibodies should be requested (HSV-specific glycoprotein G2 for diagnosis of herpes simplex virus type 2 [HSV-2] and glycoprotein G1 for diagnosis of herpes simplex virus type 1 [HSV-1]) . Low index values (1.1 to 3.5) with certain commercial assays frequently represent false-positive results ; in such cases, the presence of HSV antibody should be confirmed with a different serologic assay. Pregnancy management is based upon the serologic findings:
●If both partners are seronegative, care is routine (in monogamous couples).
●If the woman is seronegative for HSV-2 and the partner is seropositive, condoms should be used during sexual intercourse in the first and second trimesters [27,48]. Intercourse should be avoided in the third trimester as condoms do not provide absolute protection against sexual transmission. If the woman is seronegative for HSV-1 and the partner is seropositive, both sexual intercourse and oral-genital contact should be avoided during the third trimester. (See "Prevention of genital herpes virus infections", section on 'Condom use'.)
An additional option is treatment of the infected male partner with valacyclovir (500 mg/daily) to reduce the risk of sexual transmission. In a randomized trial of monogamous couples discordant for HSV-2, valacyclovir was 48 percent effective against transmission of HSV-2 . Valacyclovir would be expected to be equally effective against HSV-1, which is an increasingly common cause of neonatal HSV. Whether these data can be extrapolated to pregnancy is unknown. In addition, the use of suppressive therapy in reducing HSV transmission in same sex couples has not been evaluated. (See "Prevention of genital herpes virus infections", section on 'Chronic suppressive therapy in discordant couples' and "Sexual and gender minority women (lesbian, gay, bisexual, transgender, plus): Medical and reproductive care", section on 'Prevention of sexually transmitted infections'.)
An HSV vaccine is in development. (See "Prevention of genital herpes virus infections", section on 'Vaccine development'.)
●If the woman is seropositive for HSV-2 or HSV-1 but has no history of genital herpes lesions, we do not offer suppressive antiviral therapy . Use of suppressive antiviral therapy in this setting has not been studied. (See 'Suppressive therapy at 36 weeks' above.)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Genital herpes simplex virus infection in pregnancy" and "Society guideline links: Sexually transmitted infections".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topics (see "Patient education: Genital herpes (The Basics)")
●Beyond the Basics topics (see "Patient education: Genital herpes (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●During pregnancy, the major complication of maternal herpes simplex virus (HSV) infection is transmission to the newborn, as neonatal infection can result in serious morbidity and mortality. (See 'Vertical transmission' above.)
●The classification of genital HSV infection includes: primary, nonprimary first-episode genital, and recurrent infection (table 1). Clinical findings of HSV infection are similar in pregnant and nonpregnant women. (See 'Classification of genital HSV infections' above and "Epidemiology, clinical manifestations, and diagnosis of genital herpes simplex virus infection", section on 'Clinical features'.)
●The clinical diagnosis of genital herpes simplex virus infection is generally made by the finding of vesicular or ulcerated genital lesions and should be confirmed with laboratory testing. The approach to diagnosis of genital HSV during pregnancy depends on the clinical presentation. For women without a history of genital HSV who present with an active genital ulcer during pregnancy, we perform a direct viral test on the lesion and type-specific serologic testing. Genital HSV infection is diagnosed by a positive viral test from the lesion, and concurrent serologic testing is used to classify maternal infection (table 1). (See 'Diagnosis' above.)
●Transmission of HSV to neonates usually occurs during labor and delivery as a result of direct contact with virus shed from infected sites (vulva, vagina, cervix, perianal area). Viral shedding can occur when maternal symptoms and lesions are absent. (See 'Vertical transmission' above.)
●The highest risk for neonatal infection occurs in women with a newly acquired (primary or nonprimary first-episode) genital HSV infection near the time of delivery. The risk of neonatal infection is substantially lower in women with recurrent HSV infection. Other predictors of neonatal infection in women with viral shedding during labor include invasive fetal monitoring and premature delivery. (See 'Vertical transmission' above.)
●For women without a history of genital HSV who present with a new genital ulcer during pregnancy, we recommend empiric antiviral therapy while awaiting viral studies (Grade 1A). We use acyclovir 400 mg orally three times daily for 7 to 10 days (treatment can be extended if healing is incomplete after 10 days); valacyclovir is an alternative (table 2). Antiviral therapy can lessen the duration of lesions and viral shedding and decrease the risk of complications in the pregnant women. Most recurrent episodes are short-lived and do not require intervention for symptoms. (See 'Treatment of primary or nonprimary first-episode genital infection' above and 'Treatment of recurrent infection' above.)
●For all women who present with a genital HSV lesion anytime during pregnancy, whether with a primary, nonprimary first-episode, or recurrent infection, we recommend daily suppressive therapy at 36 weeks of gestation until the onset of labor rather than no therapy (Grade 1A). We use acyclovir 400 mg orally three times daily; valacyclovir is an alternative (table 2). Suppressive therapy reduces the risk of clinical recurrence of HSV delivery, and thus the need for cesarean delivery. However, the clinical impact on neonatal HSV is unknown. (See 'Suppressive therapy at 36 weeks' above.)
●Use of acyclovir during pregnancy appears to be safe for the fetus at all stages of pregnancy. Data are more limited but reassuring regarding the use of valacyclovir. (See 'Drug choice, dose, and safety' above.)
●Cesarean delivery can decrease but not eliminate the risk of neonatal HSV infection. For women with a history of HSV and genital HSV lesions or prodromal HSV symptoms at the time of labor, we recommend cesarean delivery (Grade 1B). For women who had a primary or nonprimary first-episode genital infection during the latter weeks of pregnancy (eg, within six weeks of delivery) but have no active lesions at the time of labor, we suggest cesarean delivery (Grade 2C). However, optimal management in such cases is unclear, and after discussion of the uncertain risks of transmission, some women may reasonably choose to forgo cesarean. (See 'Route of delivery' above.)
●Clinical decision-making for patients with preterm prelabor rupture of membranes (PPROM) and active HSV infection requires weighing the risks associated with preterm birth versus the risk of fetal/neonatal HSV infection. The risks associated with preterm birth depend on the week of gestation; the risk of fetal/neonatal HSV infection is difficult to estimate and depends, in part, on whether the woman's clinical episode represents primary or recurrent infection. (See 'Preterm premature rupture of membranes' above.)
•In women with PPROM and recurrent HSV infection, we suggest expectant management remote from term (Grade 2C). We prescribe a course of antenatal corticosteroids to pregnancies <34 weeks to reduce the morbidity and mortality related to preterm birth and intravenous acyclovir (5 mg/kg every 8 hours) to shorten the duration of active lesions and to decrease viral burden. (See 'Preterm premature rupture of membranes' above.)
•There are no clinical trials evaluating the optimum management of women with PPROM and primary or first-episode genital nonprimary HSV infection. Before 28 to 32 weeks, the risks of prematurity are high and may outweigh the risk of fetal/neonatal infection with expectant management.
-Remote from term, we give acyclovir to the mother to shorten the duration of lesions and reduce viral shedding; there are no data showing prevention of neonatal infection. We also give a course of antenatal corticosteroids to reduce the morbidity and mortality related to preterm birth.
-Closer to term, immediate cesarean delivery is preferable because of the overall high risk of fetal/neonatal transmission associated with first-episode genital HSV infection. The neonate is then treated with acyclovir and surfactant. (See 'Preterm premature rupture of membranes' above.)
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