Varicella-zoster virus infection in pregnancy

INTRODUCTION — Varicella-zoster virus (VZV) is one of eight herpesviruses known to cause human infection worldwide. Varicella infection in children is generally a mild disease, while infection in adults can lead to significant morbidity and mortality. During pregnancy, varicella pneumonia can be particularly severe and maternal infection can lead to congenital abnormalities with devastating consequences [1].

This topic will address the epidemiology, infectious complications, management and prevention of varicella in the pregnant female. The clinical manifestations, treatment and prevention of VZV infection in the nonpregnant adult are discussed elsewhere. (See "Clinical features of varicella-zoster virus infection: Chickenpox" and "Treatment of varicella (chickenpox) infection" and "Vaccination for the prevention of chickenpox (primary varicella infection)".)

Management of the newborn who has been exposed to varicella is discussed elsewhere. (See "Varicella-zoster infection in the newborn".)

GENERAL BACKGROUND — VZV infection causes two clinically distinct forms of disease: varicella (chickenpox) and herpes zoster (shingles).

Varicella — Primary VZV infection results in the diffuse vesicular rash of varicella, or chickenpox. Primary infection with VZV during pregnancy has significant implications for maternal and fetal health:

●Although fewer than 2 percent of reported cases of varicella infections occur among adults older than 20 years of age, almost a quarter of all VZV-related mortality occurs among this age group [2]. Thus, pregnant women are at risk for substantial morbidity and mortality.

●If the mother acquires varicella infection during the early gestational period (weeks 8 to 20), the fetus is at risk for developing congenital varicella syndrome [3]. This syndrome is characterized by limb hypoplasia, skin lesions, neurologic abnormalities, and structural eye damage [3]. (See 'Clinical features of congenital varicella syndrome' below.)

●Maternal varicella during pregnancy is also associated with the subsequent development of herpes zoster during infancy [3].

●If the mother acquires varicella immediately before or after delivery, the baby is at risk for neonatal varicella, which may present with mild rash to disseminated infection. Neonatal disease is discussed elsewhere. (See "Varicella-zoster infection in the newborn".)

Herpes zoster — Endogenous reactivation of latent VZV typically results in a localized skin infection known as herpes zoster, or shingles. Maternal herpes zoster infection is not associated with a significant risk of congenital varicella syndrome, although maternal varicella with subsequent embryopathy has been described in one case report where the pregnant mother touched vesicular fluid on the scalp of a person with zoster [3,4]. (See 'Congenital varicella' below.)

EPIDEMIOLOGY — Overall trends in the epidemiology of VZV infection are changing in light of the introduction of varicella vaccine in 1995. However, the incidence of varicella is not precisely known since it is not a reportable disease.

Maternal varicella — The incidence of varicella infection during pregnancy in the United States is estimated to be 1 to 5 cases per 10,000 pregnancies [5,6]. This low incidence is related to the high rates of VZV seropositivity among adults (>95 percent) [2,7,8]. Similar rates have been demonstrated in Europe, but VZV seropositivity rates among persons living in tropical areas are lower, at approximately 50 percent [9-11].

Although the incidence of varicella is not higher in pregnant compared to nonpregnant adults, disease severity appears to be increased. Varicella pneumonia is often estimated to complicate 10 to 20 percent of maternal infections [2]. However, in a study of 935 cases of maternal VZV infection identified from a large database of hospital admissions in the United States, a VZV pneumonia diagnosis was recorded in only 2.5 percent, and there were no deaths [6]. Other estimates of morbidity and mortality related to varicella pneumonia have been higher, at 3 to 14 percent in the era of antiviral treatment, down from 20 to 45 percent prior to the introduction of effective antiviral therapy [10,12,13]. Risk factors for varicella pneumonia during pregnancy include a history of smoking and having greater than 100 cutaneous vesicles [2,12].

Congenital varicella — Nine observational studies performed between 1986 and 2002 suggest that congenital varicella syndrome is uncommon [14-16]. Fewer than 2 percent of women who have acquired varicella infection during the first 20 weeks of gestation have subsequently given birth to an infant with this embryopathy [3,4,14,15,17]:

●In the largest published prospective study of 1739 cases of maternal varicella infection, the incidence of congenital abnormalities was 0.4 percent if maternal infection occurred before the 12th week of pregnancy; the risk increased to approximately two percent if maternal infection occurred between weeks 13 and 20 [3].

●In a prospective study of 362 women with maternal VZV infection (347 with varicella; 15 with zoster), only one female with varicella infection gave birth to an infant with VZV embryopathy (0.4 percent) [15].

●Only nine isolated cases of congenital varicella have been reported between weeks 21 to 28 of gestation [2].

In the largest published prospective study of maternal varicella, there were 344 cases of herpes zoster and there were no cases of congenital varicella [3]. However, there is one case report from 1987 of congenital varicella syndrome following maternal zoster [18].

Effect of varicella vaccine on VZV epidemiology — The incidence of varicella has changed over time since the introduction of the varicella vaccine in 1995. High immunization rates with one dose of varicella vaccine led to an 84 percent reduction in the number of varicella cases in the United States and an 88 percent decline in varicella-related hospitalizations [19]. Despite these improvements, varicella-related infections and breakthrough varicella disease were reported, leading to the initiation of a two-dose schedule in 2006. The vaccine efficacy of two doses over a 10-year observation period is estimated at 98 percent for the prevention of any infection and 100 percent for the prevention of severe disease [19].

A US-based survey demonstrated that the incidence of varicella infections among adults has declined by 74 percent in the decade following the introduction of varicella vaccine [20]. Since only 3 percent of the adults surveyed had been vaccinated, the substantial decline of infections was attributed to herd immunity. Although the incidence data showed a positive impact of immunization, adults who developed varicella were at higher risk of morbidity and mortality compared with children.

Epidemiologic data also suggest that varicella vaccination has reduced the number of maternal and fetal varicella infections. As an example, surveillance data from Australia from 2006 to 2009 demonstrated that the incidence of congenital varicella infection was 0.19 per 100,000 live births/annum and the incidence of neonatal infection was 2 per 100,000 live births/annum [21]. These trends represent an 85 percent reduction in varicella cases among newborns in the post-vaccination era compared to the prevaccination era. Although the incidence of congenital varicella syndrome and neonatal varicella infection remain low, Australia's surveillance data show that half of mothers delivering are born in countries where a vaccination program does not exist. Thus, pregnancy screening and postpartum vaccination remain an important intervention to avoid missed opportunities in these populations [22]. (See "Prenatal care: Initial assessment", section on 'Documentation of varicella immunity' and 'Post-exposure prophylaxis' below.)

No long-term data are available on the duration of protection of the two-dose varicella vaccine schedule [23].

TRANSMISSION — In general, the risk of transmission of VZV infection is higher with exposure to varicella compared with zoster. Persons with either illness are not considered infectious once lesions have crusted over.

Person to person — Varicella is highly communicable with secondary attack rates in susceptible household contacts approaching 90 percent in the prevaccination era [2]. Patients are infectious from one to two days prior to this rash until the lesions are crusted over.

Varicella is usually transmitted by infected secretions harbored in the nasopharyngeal mucosa by droplets onto the conjunctival or nasal/oral mucosa. Other mechanisms include direct contact with vesicular fluids that contain virus, and rarely, the airborne spread of virus.

Susceptible persons can also acquire varicella infection from exposure to persons with zoster, although the transmission rates are considerably lower and usually require close exposure to open cutaneous lesions [24].

Mother to infant — Maternal varicella infection not only has important implications for the mother’s health, but also for her fetus [12,14,15]. Transmission can occur in utero, perinatally, or postnatally [25]. Intrauterine or perinatal infection of the fetus is facilitated through transplacental transmission while postnatal varicella is transmitted through respiratory droplets or direct contact with someone with varicella [25].

Passage of varicella-zoster virus to the fetus during zoster is rare [3,15,26]. The low observed rates of transmission may be related to preexisting maternal antibody to VZV and to the generally lower levels of viremia that accompany reactivation of VZV infection (eg, shingles) compared with primary infection (eg, chickenpox) [27].

INCUBATION PERIOD — The incubation period of varicella in an adult or child is 10 to 21 days after exposure.

PATHOGENESIS — Humans are the only source of VZV infection. Primary varicella infection generally leads to lifelong immunity; case reports of reinfections are rare [28].

Maternal infection — Primary infection is followed by viral replication in regional lymph nodes and tonsils and possibly ductal tissue of salivary glands for four to six days with subsequent spread to other internal organs. After continued replication, VZV is again released into the bloodstream (secondary viremia) and invades cutaneous tissue resulting in the VZV exanthem within approximately 14 to 21 days [29].

In utero infection — The precise mechanism of in utero VZV infection is unknown. It is widely accepted that maternal viremia leads to placental infection with subsequent fetal infection; thus, prevention of maternal infection is of high priority. VZV DNA may be detected in multiple fetal organs [30]; histologic examination of the placenta demonstrates granulomas and acute inflammation.

The sites of VZV replication in the fetus are unclear. It has been suggested that the fetus develops varicella in utero followed by resolution and subsequent infection of the dorsal root ganglia [18]. This results in cell destruction in nerve tissue, which may account for limb denervation changes seen in the congenital varicella syndrome.

CLINICAL FEATURES OF MATERNAL VZV INFECTION

Uncomplicated varicella — The characteristic rash of varicella, which is usually pruritic, appears in successive crops of vesicles on the face, trunk and extremities. Thus, the patient with varicella typically has lesions in different stages of development. New vesicle formation generally stops within four days [31]. Many patients with uncomplicated varicella experience a prodrome of fever, malaise, and myalgia one to four days prior to the onset of rash.

The lesions begin as macules that rapidly become papules followed by vesicles (picture 1). These lesions can then develop a pustular component followed by the formation of crusted papules [32]. Most lesions have fully crusted by day six in normal hosts. Crusts tend to fall off within about one to two weeks and leave a temporary area of hypopigmentation in the skin [32].

Complicated infection — Varicella-related complications are more common in adults than children and include meningitis, encephalitis, cerebellar ataxia, pneumonia, glomerulonephritis, myocarditis, ocular disease, adrenal insufficiency, and death [33]. Secondary bacterial infections can also occur in patients with significant cutaneous disease.

Varicella pneumonia — The most common clinical manifestation of complicated varicella infection in pregnancy is varicella pneumonia. The predominant signs and symptoms of varicella pneumonia in pregnancy are cough, dyspnea, fever, and tachypnea [27,34]. The pneumonia usually develops within one week of the rash. The clinical course is unpredictable and may rapidly progress to hypoxia and respiratory failure. The chest x-ray findings include a diffuse or miliary/nodular infiltrative pattern often in the peribronchial distribution involving both lungs.

FETAL EFFECTS OF VZV INFECTION

Clinical features of congenital varicella syndrome — Congenital varicella syndrome, first described in 1947, is characterized by the following findings [10,35-37]:

●Cutaneous scars in a dermatomal pattern

●Neurological abnormalities (eg, intellectual disability, microcephaly, hydrocephalus, seizures, Horner’s syndrome)

●Ocular abnormalities (eg, optic nerve atrophy, cataracts, chorioretinitis, microphthalmos, nystagmus)

●Limb abnormalities (hypoplasia, atrophy, paresis)

●Gastrointestinal abnormalities (gastroesophageal reflux, atretic or stenotic bowel)

●Low birth weight

Congenital varicella syndrome is associated with a mortality rate of 30 percent in the first few months of life and a 15 percent risk of developing herpes zoster in the first four years of life [1].

Prematurity and spontaneous abortion — Varicella is not generally associated with first-trimester spontaneous abortions [1]. In several cohort studies, no significant differences in spontaneous abortion rates, premature births, or intrauterine death were noted between the maternal varicella group and the control group, although the overall number of mothers with varicella infection was small [14,38-40].

Neonatal VZV infection — Neonatal varicella infection results from VZV transmission from a mother to the fetus just prior to delivery. Neonates born to mothers who have clinical disease within five days before to two days after delivery are at the greatest risk for severe disease and poor outcome. Management of the newborn with varicella exposure and varicella infection is discussed elsewhere. (See "Varicella-zoster infection in the newborn".)

DIAGNOSIS

Maternal varicella — The diagnosis of varicella infection is clinical. If there is doubt about the clinical diagnosis, VZV infection may be rapidly confirmed through detection of viral DNA by PCR testing of skin scrapings from the base of the vesicle or through the detection of VZV antigen by immunofluorescence. VZV can also be cultured from vesicular fluid, although the virus replicates slowly and culture is less sensitive than direct detection techniques. (See "Diagnosis of varicella-zoster virus infection".)

Serologic testing is usually not necessary for diagnosis of maternal varicella, and may be potentially confusing since the assays vary in sensitivity and specificity.

The diagnosis of varicella pneumonia should be considered when a pregnant woman has typical skin lesions, contact with varicella, and respiratory symptoms. (See "Clinical features of varicella-zoster virus infection: Chickenpox", section on 'Pneumonia'.)

Congenital varicella syndrome

Prenatal diagnosis — After maternal infection, the risk of congenital varicella syndrome can be estimated using polymerase chain reaction (PCR) testing of fetal blood or amniotic fluid for VZV DNA in conjunction with ultrasonography for detection of fetal abnormalities [10,37,41,42].

PCR testing for VZV DNA is a sensitive test, which is usually obtained between 17 and 21 weeks of gestation. A detailed anatomic ultrasound evaluation should occur at a minimum of five weeks after maternal infection to assess fetal abnormalities consistent with congenital varicella syndrome (eg, microcephaly, limb hypoplasia, intrauterine growth retardation) [25].

Normal results of imaging and laboratory testing suggest a low risk of congenital varicella syndrome. A normal ultrasound with detectable VZV DNA suggests potential risk; thus, a repeat ultrasound at 22 to 24 weeks is indicated. If the repeat ultrasound is normal, the risk of congenital varicella syndrome is remote. If the ultrasound shows evidence of congenital varicella syndrome, the woman should be counseled regarding likely fetal disease [43].

Serologic testing of the fetus is of limited utility because of low sensitivity and poor specificity [3,26,37,42].

Postnatal diagnosis — The diagnosis of congenital varicella syndrome requires the following criteria [1,44]:

●History of maternal varicella infection during the first or second trimester of pregnancy

●Presence of compatible fetal abnormalities consistent with congenital varicella syndrome

●Evidence of intrauterine VZV infection

Evidence of intrauterine infection can include any of the following: detection of VZV DNA in the newborn; presence of VZV-specific IgM antibodies in cord blood; persistence of VZV IgG beyond seven months of age; appearance of clinical zoster infection during early infancy.

MANAGEMENT OF MATERNAL VZV INFECTION

Treatment of varicella infection

Uncomplicated varicella infection — We suggest oral acyclovir therapy (800 mg five times per day for seven days) for all pregnant women with uncomplicated varicella. A woman who is a secondary contact of a patient with varicella is of particular concern for treatment since secondary cases are more likely to have more severe disease. If the diagnosis is uncertain, it is reasonable to wait for confirmation, but acyclovir treatment is most effective within the first 24 hours.

The use of oral acyclovir for uncomplicated varicella infection among pregnant women has not been studied. Although animal data and observational data from large pregnancy registries do not suggest teratogenicity of acyclovir, well-controlled studies have not been performed [2]. However, a prospective registry of acyclovir-exposed pregnancies revealed no increased rate or pattern of congenital anomalies in 596 infants who were followed [45].

A randomized placebo-controlled trial in male and nonpregnant female adults with primary varicella infection evaluated the efficacy of acyclovir within 72 hours of symptom onset [46]. The trial demonstrated that acyclovir treatment was associated with faster healing of skin lesions and a shorter duration of fever, if initiated within 24 hours of symptom onset [46]. The low frequency of complicated infections (eg, varicella pneumonia) in the study population precluded evaluation of any effect of acyclovir on more severe disease.

Varicella pneumonia — Varicella pneumonia during pregnancy is a medical emergency; the mortality rate among pregnant women in the era prior to antiviral therapy approximated 36 to 40 percent in case series reports [34,47,48]. Although there are no randomized controlled trials of acyclovir for the treatment of varicella pneumonia, observational data suggest a beneficial impact of antiviral therapy on maternal mortality when compared with historical controls [12,34,48-50]:

●In a retrospective review of 21 cases of varicella pneumonia in pregnant women treated with acyclovir, the mortality rate was 14 percent, a value lower than expected in untreated women [34].

●In an observational study, all 18 patients with varicella pneumonia, who were treated with acyclovir, survived [12]. Twelve patients required intubation and mechanical ventilation.

We recommend intravenous acyclovir (10 mg/kg every eight hours) for pregnant women with varicella pneumonia. The risk-benefit of treatment of maternal varicella infection outweighs any theoretical concerns regarding fetal toxicity; no specific pattern of congenital malformations has been attributed to acyclovir in large pregnancy registries [51].

Although acyclovir crosses the placenta, it is unknown if this antiviral agent decreases the risk of congenital varicella syndrome [52].

Treatment of herpes zoster infection — Management of herpes zoster during pregnancy is similar to that in nonpregnant adults. (See "Treatment of herpes zoster", section on 'Pregnancy'.)

POST-EXPOSURE PROPHYLAXIS — Prevention is targeted to susceptible hosts who do not have a history of infection or serologic evidence of prior exposure.

Evaluating susceptibility — A self-reported history of varicella among pregnant women is a powerful predictor of antibodies to varicella infection [8]. In addition, most women without a history of varicella have serologic evidence of past infection.

These concepts were well-illustrated in a study of pregnant females where more than 98 percent of 837 pregnant females with a history of varicella infection had serologic evidence of past infection [8]. In addition, only a minority of women, who reported a negative or uncertain history of varicella, was subsequently confirmed to be seronegative for varicella antibodies (ie, 7 and 17 percent, respectively).

Ideally, a VZV serologic test should be conducted prior to administration of immunoprophylaxis among those women who report no history of varicella [53]; such a strategy is cost-effective and suggested by some experts [54-56]. However, rapid screening is necessary since prophylaxis should be offered within ten days of exposure. If results of serologic testing are not available within this time frame, then postexposure prophylaxis should be offered.

Evidence of immunity is discussed in greater detail elsewhere. (See "Post-exposure prophylaxis against varicella-zoster virus infection".)

Defining exposure — Among nonimmune pregnant women, it is important to review the exposure of concern.

Significant exposure to varicella infection, which is highly contagious, is defined as household contact, face to face contact with an index case for five minutes, or sharing the same hospital room with a contagious patient.

Herpes zoster is much less contagious and usually requires close contact or exposure to open cutaneous lesions for transmission to occur [4], although rare cases of airborne transmission have been reported in nosocomial settings. Nonimmune women who have had such exposures to zoster infection should also be considered for postexposure prophylaxis since they are at risk for primary varicella infection. (See "Prevention and control of varicella-zoster virus in hospitals" and "Prevention and control of varicella-zoster virus in hospitals", section on 'Transmission from persons with zoster'.)

Immunoprophylaxis for the prevention of maternal varicella infection — Passive immunization with VZV-specific antibodies reduces the risk of varicella infection and also attenuates the severity of infection in those who seroconvert [55]. The US Advisory Committee on Immunization Practices recommends Varizig, a varicella-zoster immune globulin preparation, in all nonimmune pregnant women who have been exposed to persons with VZV [2,57]. Postexposure prophylaxis is not needed among women who were immunized with varicella vaccine in the past.

Patients need careful follow-up for signs of infection despite passive immunization. Those who are infected despite postexposure prophylaxis should be treated for varicella infection. (See 'Treatment of varicella infection' above.)

Susceptible pregnant women who receive postexposure prophylaxis and do not develop varicella should undergo vaccination against varicella after delivery and at least five months following administration of immunoprophylaxis [57]. (See 'Nonpregnant females' below.)

Which product should be used? — Varizig is the only formulation of varicella-zoster immune globulin used for passive immunization in the United States. Products used in the past included ZIG and VZIG. Data on the use of Varizig during pregnancy are discussed below. (See 'Varizig' below.)

If Varizig cannot be obtained, then intravenous immune globulin (IVIG) can be considered. (See 'Intravenous immunoglobulin' below.)

Further details on the efficacy of immunoprophylaxis are discussed elsewhere. (See "Post-exposure prophylaxis against varicella-zoster virus infection", section on 'Passive immunoprophylaxis'.)

Varizig — Varizig, a formulation of varicella-zoster immune globulin, is a purified human immune globulin preparation made from plasma containing high levels of anti-varicella antibodies. Varizig undergoes filtration and inactivation to decrease the transmission of known viruses such as HIV and hepatitis viruses.

Varizig should be administered intramuscularly as soon as possible within 10 days of exposure. Limited data suggest that the incidence of varicella is comparable among people who receive passive immunization within four days or within 5 to 10 days of varicella exposure [54,58,59]. The efficacy of passive immunization after this time interval is not known [60]. Detailed information on dosing and administration is described in the varicella-zoster immune globulin drug information monograph within UpToDate.

In a study of 60 pregnant females who were randomly assigned to receive either Varizig or VZIG after varicella exposure, the efficacy and safety of the two products were similar over the 28-day period of follow-up; 29 percent developed varicella in the Varizig group compared with 42 percent in the VZIG arm [54]. These rates of infection were lower than historical controls (ie, >90 percent).

Intravenous immunoglobulin — For pregnant women who cannot receive Varizig within 10 days of exposure, clinicians may choose either to administer a single dose of intravenous immune globulin (IVIG) at 400 mg/kg [24] or closely monitor for signs and symptoms of varicella and institute treatment with acyclovir if illness occurs. IVIG is not routinely screened for antibodies against varicella virus. (See "Post-exposure prophylaxis against varicella-zoster virus infection", section on 'Administration'.)

Immunoprophylaxis for the prevention of congenital varicella syndrome — Due to the rarity of congenital varicella syndrome, there are no definitive data that immunoprophylaxis prevents embryopathy among women who develop varicella despite prophylaxis.

The primary reason to offer immunoprophylaxis to all VZV-exposed pregnant females is to decrease the risk of maternal infection and maternal morbidity [61]. Women who are protected from acquiring varicella are not at risk of having an infant with congenital varicella syndrome. Among women who do acquire VZV despite immunoprophylaxis, it is biologically plausible that passive immunization might decrease viremia, leading to a lower risk of mother-to-child transmission. (See 'Immunoprophylaxis for the prevention of maternal varicella infection' above.)

In a prospective cohort of 1739 women who had varicella or herpes zoster during gestation, 97 women had received VZIG to prevent varicella infection [3]. There were no cases of congenital varicella syndrome among the infants born to women who had received prophylaxis; however, the overall risk of congenital varicella syndrome was also low among infants born to women who did not receive prophylaxis (0.7 percent; 9 cases of 1373 women with varicella). No cases of congenital varicella syndrome were diagnosed among women with zoster.

Antiviral therapy — There are no data on whether acyclovir is beneficial in reducing the risk of varicella after exposure during pregnancy.

PRE-EXPOSURE PROPHYLAXIS — VARIVAX, a live attenuated varicella vaccine, is recommended by the ACIP for susceptible children under age 13 years and susceptible young adults [2,19]. The estimated vaccine efficacy over a 10-year observation period of two doses for prevention of varicella is 98 percent with 100 percent efficacy for prevention of severe disease [19]. The seroconversion rate after vaccination is approximately 82 percent in adults and 91 percent for children.

Nonpregnant females — The negative effects of varicella infection on maternal, fetal and neonatal morbidity and mortality are preventable with varicella immunization prior to onset of pregnancy [27]. The Advisory Committee on Immunization Practices recommends that all women of child-bearing age be assessed prior to conception for evidence of varicella immunity by either [2,8]:

●A history of previous vaccination

●Prior varicella infection

●Laboratory evidence of immunity

Nonpregnant women who do not have evidence of immunity to varicella should be offered the standard dosing of vaccine (ie, 2 doses four to eight weeks apart) to prevent varicella-related morbidity and mortality. One analysis suggested that such a universal approach is more cost-effective than offering immunoprophylaxis to women during pregnancy for postexposure prophylaxis [62].

Women should avoid becoming pregnant for one month after immunization because of theoretical concerns regarding risk to the fetus [2,63].

Pregnancy — Pregnant women should not receive this live vaccine because of the theoretical risk of inducing congenital disease. However, if a pregnant woman is found to be nonimmune during pregnancy, varicella vaccine should be recommended immediately after delivery with the second dose administered at the six-week postpartum visit.

Immunizations during pregnancy and the breastfeeding period are discussed in detail elsewhere. (See "Immunizations during pregnancy".)

Household contacts of pregnant women — Household contacts of a pregnant woman, regardless of her susceptibility to varicella, can receive the varicella vaccine when indicated, without delay.

The risk of transmission of VZV from a healthy individual who received the varicella vaccine to a healthy but susceptible household contact is extremely low [2,64]. There is only a single case report of transmission to a susceptible pregnant woman; she was infected with the vaccine strain virus after her 12-month old child developed vesicular lesions following the varicella vaccine [65]. The potential risk of transmission of vaccine virus is probably smaller than the risk of an unimmunized child developing varicella and transmitting it to a susceptible mother. The risk for vaccine virus transmission is higher when vaccinees are immunocompromised and develop a varicella-like rash, but varicella vaccine is generally not recommended for immunocompromised hosts. (See "Vaccination for the prevention of chickenpox (primary varicella infection)", section on 'Immunocompromised hosts'.)

Thus, there is no indication to delay vaccination of household contacts to prevent possible transmission of varicella. However, if a household contact develops skin lesions following varicella vaccination, susceptible pregnant women should avoid close contact with that individual until the lesions resolve, if possible. Evaluation for possible administration of Varizig for post-exposure prophylaxis is warranted in this situation. (See 'Post-exposure prophylaxis' above.)

INFECTION CONTROL — Infection control measures for individuals with varicella are discussed elsewhere. (See "Prevention and control of varicella-zoster virus in hospitals", section on 'Isolation precautions for patients with varicella'.)

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: Varicella-zoster virus".)

SUMMARY AND RECOMMENDATIONS

●Varicella-zoster virus (VZV) infection causes two clinically distinct forms of disease: varicella (chickenpox) and herpes zoster (shingles). Varicella is generally a mild, self-limited illness in healthy children, but can occasionally lead to serious morbidity during pregnancy. (See 'Introduction' above.)

●The incidence of varicella is low among adults because most are immune to infection. Although the incidence of varicella is not increased in pregnant compared with nonpregnant adults, disease severity appears to be higher during pregnancy. (See 'Maternal varicella' above.)

●Among women who develop varicella infection during pregnancy, the risk of congenital varicella syndrome appears to be small (0.4 to 2 percent). (See 'Congenital varicella' above.)

●Varicella is highly communicable, with secondary attack rates in susceptible household contacts approaching 90 percent in the prevaccination era. Patients are infectious from one to two days prior to this rash until lesions are crusted over. Mother-to-child transmission of VZV can occur in utero, perinatally, or postnatally. (See 'Transmission' above.)

●The vesicular rash of varicella appears in successive crops over several days on the face, trunk and extremities. (See 'Uncomplicated varicella' above.)

●One of the most common maternal clinical manifestations of complicated varicella infection in pregnancy is varicella pneumonia. The clinical course is unpredictable and may rapidly progress to hypoxia and respiratory failure, with high rates of mortality in untreated infection. (See 'Clinical features of maternal VZV infection' above.)

●Congenital varicella syndrome is characterized by cutaneous scars, intrauterine growth retardation, and neurological, ocular and limb abnormalities. (See 'Fetal effects of VZV infection' above.)

●The diagnosis of maternal varicella infection is clinical, based on the characteristic vesicular rash. (See 'Maternal varicella' above.)

●After maternal infection, the risk of congenital varicella syndrome can be estimated using polymerase chain reaction (PCR) testing of fetal blood or amniotic fluid for VZV DNA, in conjunction with ultrasonography for detection of structural fetal abnormalities. (See 'Congenital varicella syndrome' above.)

●Antiviral therapy with acyclovir in nonpregnant adults improves skin healing and the duration of fever, if initiated within 24 hours of symptom onset. There are no data to suggest that acyclovir prevents the development of complicated infection. A large prospective registry of acyclovir-exposed pregnancies suggests that acyclovir is not teratogenic, although large controlled trials have not been performed. We suggest oral acyclovir for pregnant women with uncomplicated varicella (Grade 2C). (See 'Management of maternal VZV infection' above.)

●Although there are no direct controlled trials in nonpregnant or pregnant adults, mortality rates secondary to varicella pneumonia appear significantly lower with treatment compared with untreated historical controls. We recommend acyclovir for all pregnant women with varicella pneumonia (Grade 1B). Acyclovir should be administered intravenously at 10 mg/kg every eight hours in patients with complicated varicella infection. (See 'Varicella pneumonia' above.)

●Postexposure prophylaxis is targeted to susceptible pregnant women (eg, those without a history of varicella or those who are seronegative) who have had a significant exposure to a person with varicella or zoster. Since many women have serologic evidence of past infection, it appears cost-effective to serologically screen prior to prophylaxis, when feasible. (See 'Evaluating susceptibility' above.)

●Immunoprophylaxis (eg, Varizig) is associated with a lower risk of acquisition of varicella after exposure and milder illness in those who seroconvert despite postexposure prophylaxis. Persons who undergo immunoprophylaxis need careful follow-up for symptoms of varicella infection. (See 'Immunoprophylaxis for the prevention of maternal varicella infection' above.)

●We recommend postexposure prophylaxis with an immunoglobulin product containing high titers of VZV-specific antibodies compared with watchful waiting (Grade 1B). In the United States, Varizig is the only available product with VZV-specific antibodies. Administration of Varizig should occur within 10 days of exposure. (See 'Varizig' above.)

●The negative effects of varicella infection on maternal, fetal and neonatal morbidity and mortality are preventable with varicella immunization prior to onset of pregnancy. The safety and efficacy of varicella vaccination is discussed in detail elsewhere. (See 'Pre-exposure prophylaxis' above and "Vaccination for the prevention of chickenpox (primary varicella infection)".)