Virology
Chickenpox (varicella) is caused by a highly contagious DNA herpes virus. Varicella-zoster virus (VZV) is the virus responsible for varicella (chickenpox) and herpes zoster (“shingles”). VZV is a member of the herpes virus family, which includes herpes simplex virus (HSV) types 1 and 2, cytomegalovirus (CMV), Epstein-Barr virus (EBV), and human herpes virus (HHV-6, HHV-7, and HHV-8). Varicella results from primary VZV infection; it is a common childhood illness associated with fever and a generalized pruritic vesicular rash [2].
Incidence
Chickenpox is an uncommon disease during pregnancy as 93–95 % women of childbearing age are seropositive with virus-specific IgG antibodies. The incidence of varicella is 0.7–3/1000 pregnancies [3].
Clinical Features
1.
Chicken pox is transmitted by respiratory droplets and by direct personal contact with vesicle fluid or indirectly via fomites. It is characterized by fever, malaise, dry cough, and pruritic rash. Varicella-zoster virus (VZV) is 25 times more serious in adults than in children. The incubation period of chickenpox is 10–21 days [3].
2.
The primary infection is characterized by fever, malaise, and a pruritic rash. The rash goes through three stages. Initially, it is red and itchy, resembling insect bites, and appears on face, scalp, chest, and back. It then evolves into crops of maculopapules which become vesicular and crust over in next 4–5 days before healing. The vesicular skin lesion is the hallmark of the disease. A total number of 300–400 rashes may appear over the body. The rash may persist for 20 days and begins 48 h after the onset of headache, malaise, and fever. New lesions emerge throughout the first week. The lesions cloud and umbilicate and then crust over. The vesicles usually crust over within 5 days. The vesicles can be easily ruptured and oozes serous fluid. The contact with skin fluid can be another mode of disease transmission [4]. The infection is characterized by the simultaneous development of lesions at various stages; as a result, all three stages of the rash maculopapular, blisters, and scabbed lesions can be present at the same time. The patient is contagious until all of the lesions have crusted [3].
3.
Complications include infection of skin lesions, scarring, pneumonia, and, rarely, cerebral edema and death.
4.
Diagnosis of chicken pox, either in pregnant or nonpregnant subjects, can be easily performed on the basis of clinical history and clinical classical signs or symptoms. Laboratory workup may not be required. Available laboratory tests include virus/viral antigen detection, virus isolation, and identification or serological diagnosis. These may be useful in atypical cases.
Pregnancy and Chickenpox
There is no difference in clinical presentation of chicken pox in pregnancy as compared to the nonpregnant.
The pregnant woman develops high fever that can last for up to 7 days. The diagnosis of varicella is usually made clinically. The virus may be cultured from vesicular fluid, but this is a cumbersome process. Serologic tests may help document acute infection in confusing cases or indicate immunity. IgM antibody may be detected as soon as 3 days after symptoms appear, and IgG may be detected as early as 7 days after varicella symptoms. Multiple antibody detection assays are available including fluorescent anti-membrane antibody (FAMA), latex agglutination (LA), enzyme-linked immunosorbent assay (ELISA), and complement fixation tests [5].
Maternal Risks
Anecdotally, chickenpox infection in pregnancy is more severe than in nonpregnant adults.
Risks depend on when the infection developed during pregnancy. There could be increased severity of illness in the second half of pregnancy.
Varicella, the primary infection with varicella-zoster virus in pregnancy, may cause maternal mortality or serious morbidity [6]. The infection can cause pneumonia, hepatitis, and encephalitis. Pneumonia can occur in up to 10 % of pregnant women with chickenpox, and the severity increased in later gestation. Even a healthy pregnant woman is at risk of dying if she develops varicella pneumonia. Mortality rates between 20 and 45 % were reported in the pre-antiviral era but have fallen to 3–14 % with antiviral therapy and improved intensive care [7].
The chance of preterm labor is increased. Mechanism of the increased prevalence of preterm labor is unknown. It is tempting to speculate on the production of inflammatory mediators due to the viremia as being related to the preterm labor [5].
Maternal Varicella Pneumonia
Serious life-threatening complications of the infection include pneumonia (up to 20 % of pregnant patients) and encephalitis (up to 1 % of pregnant patients).
Maternal pneumonia complicates about 10–20 % of cases of chickenpox in pregnancy resulting in a higher mortality/morbidity than in nonpregnant adults. Pregnant women with VZV pneumonia should be hospitalized for monitoring and to initiate antiviral therapy because up to 40 % of women may need mechanical ventilation [8]. Mortality in severe cases (those who require mechanical ventilation) in the pre-antiviral era was 20–45 % and is currently estimated to be 3–14 %. Between 1985 and 2002, in the confidential enquiries into maternal deaths in the UK, there were nine indirect and one late maternal death associated with maternal VZV pneumonia [9]. The risk for pneumonia also increases with increasing gestational age. While this has been associated with relative maternal immunosuppression, it still remains unproven and may be purely mechanical with increasing splinting of the diaphragm as the gravid uterus occupies more space.
Fetal and Neonatal Risks
The transmission rate during maternal viremia has been estimated at approximately 25 %. The consequences for the infant depend on the time of maternal infection [10].
The fetal involvement has been traditionally divided into three forms:
“Varicella embryopathy”: stemming from maternal disease occurring before 20 weeks of gestation
Congenital varicella resulting from maternal infection from 20 weeks gestation to term but more commonly close to term
Neonatal disease occurring when the pregnant patient has active lesions around the time of delivery
The infection rate for fetus has been reported to range from 12 to 30 % [3].
Infection before 20 Weeks of Pregnancy
Women who experience chicken pox early in their pregnancy have a very low chance of infecting their unborn baby. The risk appears to be approximately 2 % if the infection occurs before 20 weeks and less than 1 % if it occurs before 13 weeks [11].
The risk of spontaneous miscarriage is not generally increased if chicken pox occurs in the first trimester.
Varicella embryopathy was first described by Laforet and Lynch in 1947. The embryopathy includes limb hypoplasia, skin scarring, central nervous system involvement, and other skeletal lesions. Although it is most common before 20 weeks’ gestation, the embryopathy has been reported from infection as late as 26 weeks (0.4 % from conception to 13 weeks and 2.2 % from 13 to 20 weeks) [10].
Infection before 28 Weeks of Pregnancy
Congenital varicella can result from maternal infection after 20 weeks gestation.
Fetal varicella syndrome occurs in 1–2 % of maternal varicella infection. It is characterized by skin scarring, eye defects, microcephaly, cataract, hypoplasia of limbs, gastrointestinal and urogenital malformations, neurological abnormalities including cerebellar dysplasia (microcephaly, cortical atrophy, mental retardation), and bladder and bowel sphincter dysfunction [11]. Most of these malformations can be seen by ultrasound.
Perhaps the most interesting aspect of congenital varicella is a theory advanced by Higa and co-workers [12]. These authors have postulated that the skin lesions, limb defects, and central nervous system lesions represent zoster infections in utero and that the fetal effects of varicella embryopathy are sequelae of repeated zoster infections in the fetus, including in utero encephalitis. This would explain many of the types of lesions and also the frequent appearance of active vesicles when children are born.
Between 28 and 36 Weeks of Pregnancy
The late infection is not associated with adverse fetal effect.
It may present as shingles in the first few years of life (reactivation of virus after a primary infection in utero).
After 36 Weeks to Birth
The baby may become infected and could be born with chickenpox. The timing of maternal infection in relation to delivery determines the risk to the infant – transplacental inoculum vs protective maternal antibody.
Around the Time of Birth
If varicella manifests in the mother more than 5 days before delivery, there is essentially no risk to the neonate, probably because varicella antibodies have transferred to the fetus [11]. If the mother develops the rash up to 7 days after delivery when cord blood VZV IgG is low [13], the increased peripartum severity is attributed to a large transplacental inoculum of virus in the absence of protective maternal antibody.
Immunoglobulin G (IgG), immunoglobulin M (IgM), and immunoglobulin A (IgA) are produced 2–5 days after the initial infection and reach a maximum after 2–3 weeks. However, maternal varicella infection between 5 days before and 2 days after delivery poses a substantial risk to the neonate. Neonatal varicella is a severe infection that manifests with skin lesions and pneumonia and has a mortality rate of up to 31 %. In the first 10 days of life, up to 50 % of these infants will be affected. The risk of developing severe chicken pox is more if their mother has a rash 4 days before or 2 days after the birth. However, this is extremely rare (1 in 17,000 pregnancies). Furthermore, direct contactor respiratory droplet can lead to infection after birth.
Infection with onset more than 7 days before delivery ensures adequate transplacental passage of specific anti-VZV antibody to protect the infant. Passive immunization of the baby by giving VZIG immediately after delivery prevents or attenuates neonatal varicella and is essential.
Elective delivery should normally be avoided until 5–7 days after the onset of maternal rash to allow for the passive transfer of antibodies from mother to child [13].
Neonatal varicella presents as generalized chicken pox with a fatality rate of 30 %. Congenital varicella is characterized by skin lesions, limb hypoplasia, eye diseases, and neurological defects. About 25 % of infants born with these lesions die during the first months of life.
Diagnosis of Fetal Infection and Role for Prenatal Invasive Procedures
Pathogenesis unclear – possibly VZV reactivation in utero. Prenatal diagnosis is by detailed ultrasound examination and detection of VZV DNA by PCR in amniotic fluid.
No treatment
Detailed ultrasound examination: The findings appear 5 weeks later and include limb deformity, microcephaly, hydrocephalus, soft tissue calcification, and IUGR [14]. The wide spectrum of clinical manifestations in a neonate from maternal varicella included bowel obstruction, urinary tract anomalies, and microtia [15].
Fetal magnetic resonance imaging (MRI): can be useful to identify morphological abnormalities.
VZV DNA can be detected by polymerase chain reaction (PCR) in amniotic fluid [16].
VZV DNA has a high sensitivity but a low specificity for the development of FVS.
If amniotic fluid is PCR positive for VZV and the ultrasound is normal at 17–21 weeks, the risk of FVS is low.
If repeat ultrasound is normal at 23–24 weeks, the risk of FVS is remote.
The risk of FVS is very high if the ultrasound shows features compatible with FVS and the amniotic fluid is positive [16].
Management During Pregnancy
General Management
Avoid contact with susceptible individual.
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