**3.3 Parvovirus**

Parvovirus, a non-enveloped single-stranded DNA virus, is the only member of the *Parvoviridae* family known to cause human disease. Failure to produce the virus in cell culture has made it difficult to elucidate the pathophysiology. The symptoms of parvovirus B19-related infection are usually related to the host's immunological and hematological status. Since the immunological functions of the fetus are not optimum, parvovirus B19 infection may cause intrauterine infection, presenting as fetal anemia, hydrops fetalis, congenital malformations, and at times fetal-neonatal death [108].

**29**

*The Pathogenesis of Congenital Anomalies: Roles of Teratogens and Infections*

The vertical transmission of acute infection during pregnancy happens in 17–33% of the cases of maternal infection. Intrauterine infection is often asymptomatic. The fetus is highly susceptible to erythroid hypoplasia due to parvovirus B19 infection, and due to the shorter life span of fetal erythrocytes and the destructive effect of the virus, especially on rapidly proliferating erythrocytes, severe aplastic anemia may develop with the consequent hydrops fetalis. In addition to anemia, thrombocytopenia, leukopenia, elevated transaminase, and increased bilirubin, espy direct may also occur. Intrauterine parvovirus infections may also cause central nervous system anomalies. Fetal loss rate due to parvovirus B19 infection in pregnancy has been reported to be 3–9% and that of hydrops fetalis as 18% [109]. Overall the short-term prognosis of neonates with intrauterine parvovirus

If parvovirus B19 is diagnosed during pregnancy, serial fetal monitoring by Doppler ultrasonography to measure the fetal middle cerebral artery flow velocity in order to evaluate the need of intrauterine fetal blood transfusion is important. The mortality is reduced from 50 to 18% with intrauterine erythrocyte transfusion in conditions of hydrops and/or anemia detected antenatally. One transfusion is often sufficient [110]. The infection usually does not cause intrauterine death if appropriate transfusion and other supportive treatments are provided, and the fetus if born alive has good prognosis [109, 111]. Currently, no specific antiviral

CMV is the most common organism causing congenital infection around the world. The frequency is reported as 5–12/1000 live births. The risk of transmission increases with increasing gestational age, but the severity of fetal disease decreases. Approximately 10–15% of the fetuses infected in early pregnancy are symptomatic at birth, and in those cases severe systemic invasive disease marked by intrauterine growth restriction, hepatosplenomegaly, cholestasis, transaminitis, abnormal liver function tests, pneumonia, pancytopenia, hemolytic anemia, petechia, purpura, and central nervous system anomalies is noted [112]. Central nervous system findings in congenital CMV infection are quite diverse. Microcephaly, sensorineural hearing loss, chorioretinitis, and convulsion are the most common presentations. Abnormal neuroradiological findings, including ventriculomegaly-hydrocephalus, increased periventricular echogenicity and calcification, white matter involvement, and lenticulostriate vasculopathy, are detected in 70% of the cases. Neuronal migration anomalies, temporal cystic periventricular leukomalacia, occipital intraventricular septa, cerebral atrophy, corpus callosum dysgenesis, and cerebellar

The inflammation process in the placenta infected with CMV is characterized by ICAM-1 expression on the membranes of placental trophoblasts, with enhancement in the adhesion of maternal blood cells [114]. During the mother's primary infection, virus-bearing infectious leukocytes transmit CMV infection to the trophoblasts, and through the trophoblasts, the CMV reaches the stromal fibroblasts and fetal endothelial capillary cells [115]. Further in the process the virus is directed toward and proliferates in the major target fetal organs, namely, the brain, liver, inner ear, spinal cord, kidney, and the vascular epithelium. Viral DNA replication takes place in the infected organs with the production of infectious viral progeny. Neurons, oligodendroglia, microglia/macrophages, and neural progenitor/ stem cells, especially astrocytes, are particularly predisposed to CMV infections and may act as hosts in the replication and assist in the spread of the virus. The activated apoptosis during organogenesis is the important mechanism that leads

*DOI: http://dx.doi.org/10.5772/intechopen.92580*

B19 infections is reported to be good.

agent or vaccine is available for parvovirus B19.

hypoplasia are other relatively uncommon findings [113].

**3.4 Cytomegalovirus (CMV)**

**Figure 5.** *Chorioretinitis, cataract, and blueberry muffin skin rash due to congenital rubella.*

#### *The Pathogenesis of Congenital Anomalies: Roles of Teratogens and Infections DOI: http://dx.doi.org/10.5772/intechopen.92580*

The vertical transmission of acute infection during pregnancy happens in 17–33% of the cases of maternal infection. Intrauterine infection is often asymptomatic. The fetus is highly susceptible to erythroid hypoplasia due to parvovirus B19 infection, and due to the shorter life span of fetal erythrocytes and the destructive effect of the virus, especially on rapidly proliferating erythrocytes, severe aplastic anemia may develop with the consequent hydrops fetalis. In addition to anemia, thrombocytopenia, leukopenia, elevated transaminase, and increased bilirubin, espy direct may also occur. Intrauterine parvovirus infections may also cause central nervous system anomalies. Fetal loss rate due to parvovirus B19 infection in pregnancy has been reported to be 3–9% and that of hydrops fetalis as 18% [109]. Overall the short-term prognosis of neonates with intrauterine parvovirus B19 infections is reported to be good.

If parvovirus B19 is diagnosed during pregnancy, serial fetal monitoring by Doppler ultrasonography to measure the fetal middle cerebral artery flow velocity in order to evaluate the need of intrauterine fetal blood transfusion is important. The mortality is reduced from 50 to 18% with intrauterine erythrocyte transfusion in conditions of hydrops and/or anemia detected antenatally. One transfusion is often sufficient [110]. The infection usually does not cause intrauterine death if appropriate transfusion and other supportive treatments are provided, and the fetus if born alive has good prognosis [109, 111]. Currently, no specific antiviral agent or vaccine is available for parvovirus B19.
