Updated 2006-01-18 by Juliana Leite, MD

Original text 1999-07-24 Philippe Jeanty, MD, PhD & Sandra R Silva, MD

Synonyms: Congenital varicella syndrome, varicella embryopathy, chickenpox, herpes zoster.

Definition: Fetal varicella zoster is a combination of abnormalities of multiple organs, caused by fetal contamination with maternal chickenpox infection.

Incidence: The incidence of maternal infection with herpes virus varicella is 7:10,000 pregnancies. The risk of fetal involvement among all pregnant women infected with varicella during their gestation varies from 1% to 20%. First trimester varicella infections have been associated with an increased risk of spontaneous abortion. Second trimester varicella infections have been associated with 2% risk of a congenital; syndrome characterized by limb hypoplasia, cutaneous scars, cataracts, microcephaly and cortical atrophy.

Etiology: Herpes virus.

Recurrence risk: Less than 1%.

Diagnosis: Maternal infection at any time in pregnancy exposes the fetus to a high risk of transplacental contamination and is indicative of fetal follow-up. The risk of fetal anomalies, however, is higher during the first and second trimesters. Sonographic signs of fetal disease include fetal demise, growth restriction, musculoskeletal abnormalities such as clubfeet and abnormal position of the hands (caused by both necrosis and denervation of the affected tissue), limitation of limb extension due to cicatrices formation, cutaneous scars, limb hypoplasia, chorioretinitis, congenital cataracts, microphthalmia, hydrops, polyhydramnios, hyperechogenic hepatic foci, cerebral anomalies such as ventriculomegaly or atrophy, and microcephaly, disseminated foci of necrosis and microcalcifications, encephalitis, echogenic bowel in the second trimester. The placenta can show a multifocal chronic villitis with multinucleated giant cells. Fetal infection can be demonstrated by detection of varicella-zoster virus DNA by polymerase chain reaction (PCR) in fetal blood and amniotic fluid or by detection of the specific IgM antibody, in the same fluids.

Figure 1: Transverse image of fetal abdomen at 20 weeks showing multiple hyperechoic echoes in the liver. (Reprint with permission from Hayward et al³).

Figure 2: Transverse image of abdomen immediately after birth showing scattered bright echoes throughout liver. (Reprint with permission from Hayward et al).

Figure 3: Chest x-ray of newborn showing elevation of right hemidiaphragm and hypoplasia of right clavicle. (Reprint with permission from Hayward et al).

Figure 4: The brain of a fetus at 18 weeks, two weeks after maternal clinical varicella. Note the normal appearance of the falx cerebri, choroid plexus and cerebral hemispheres. (Reprint with permission from Lebel et al).

Figure 5: The fetal face at autopsy (26 weeks). Note the collapsed cranium, intact skin (very little maceration), disproportionate necrosis of the ocular globes and flattened midface. (Reprint with permission from Lebel et al¹).

Pathogenesis: Direct damage to fetal tissues by neurotropic virus.

Associated anomalies: Congenital anomalies from multiple organs with variable severity can be associated with varicella embryopathy. Among survivors, development of mental retardation, seizures, and limitation of movements may happen after birth. The virus may cause serious infections, particularly pneumonia, in adult women.

Differential diagnosis: Other viral infections, vascular accidents, amniotic band syndrome.

Prognosis: The severity of fetal involvement varies from dermatologic lesions to lethal disseminated disease. Limited scarring tends to have an excellent prognosis. Fetal brain disruptions, or severe maternal varicella with development of lethal maternal pneumonia and/or encephalitis, have an extreme high risk for fetal demise. Mortality rate varies from 39% to 61%. Early maternal infection (first and early second trimester) has a higher association with fetal anomalies, and third trimester infections have a higher risk for varicella-zoster development at the neonatal period. A life-threatening illness may occur when a newborn is delivered within 5 days of the onset of maternal illness.

Management: Termination of pregnancy can be offered before viability. If continuation of the pregnancy is chosen, periodic sonographic evaluation is recommended to search for fetal anomalies, limb contractures, and other signs of fetal compromise. If maternal seroconversion is suspected for the varicella-zoster virus, combining prenatal ultrasound and magnetic resonance imaging may document the extent of tissue damage and assist in the counseling. After a therapeutic abortion, fetal infection can be confirmed by detection of VZV DNA in several fetal tissues and placenta, and by histopathological findings like miliary calcified necroses in fetal organs.

Prevention: Serological testing, and vaccination, should be offered to women of child-bearing age and they should be questioned about immunity to varicella preconceptually. Susceptible pregnancy patients should be counseled to avoid contact with individuals who have chickenpox. If exposure occurs, VZIG should be administered within 96 hours in an attempt to prevent maternal infection. Also susceptible neonates should receive VZIG. Acyclovir is active against the varicella-zoster virus, and treatment is indicated in seriously ill adults and neonates.

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