Maternal transmission of the virus probably occurs via respiratory droplets or direct contact with chickenpox or zoster lesions. The virus replicates in the oropharynx, and viremia results, before the onset of rash, with transplacental passage to the fetus. Almost all cases reported have involved exposure between the 8th and 20th weeks of pregnancy. The pathogenesis of fetal varicella syndrome (FVS) may reflect disseminated infection in utero or as a consequence of failure of virus–host interaction to result in establishment of latency, as normally occurs in postnatal VZV infection. Since VZV is a lymphotropic virus, it has the potential to spread to all fetal organs by the hematogenous route. Pathology specimens from aborted fetuses with VZV infection have shown the virus to be distributed throughout fetal tissues. Microcephaly can be attributed to VZV encephalitis and irreversible damage to growth of the developing brain. Of interest, the virus does not appear to cause intrauterine damage to the lungs or liver in infants with FVS, as it can in perinatal varicella or in other immunocompromised hosts. Fulminant infection involving these organs may result in fetal demise, rather than birth of an infant with FVS. VZV is also a neurotropic virus; many of the defects have been postulated to be a direct result of spinal cord and ganglia infection, which causes destruction of the plexi during embryogenesis, leading to denervation of the limb bud and subsequent hypoplasia. Failure of muscle development has consequences for limb bone formation. The cutaneous defects are also likely to reflect VZV infection of sensory nerves. VZV infection of cells in developing optic tracts also explains the optic atrophy and chorioretinitis. From the pattern of dermatomal distribution of the skin defects seen in FVS, particularly the scarring and limb hypoplasia, it has been suggested that FVS is the result of intrauterine herpes zoster. The extremely short latent period between fetal infection and reactivation, if latency is established at all, is the consequence of the lack of cell-mediated immunity in the fetus before 20 weeks' gestation. Infants exposed to VZV in utero also can develop unapparent varicella and subsequent zoster early in life without having had extrauterine varicella.