Detection of Parvovirus B19, Cytomegalovirus, and Enterovirus Infections in Cases of Intrauterine Fetal Death

Abstract

In Sweden, between 6% and 20% of fetal deaths are ascribed to infectious diseases, and a substantial number of these are associated with maternal viral infections. In this prospective study, extending over 38 months, placental biopsies, fetal blood, and amniotic fluid were collected in 52 cases of intrauterine fetal death (IUFD). Biopsies from 53 normal pregnancies at term made up a control group. Tissues were examined by the polymerase chain reaction (PCR) technique for parvovirus B19 DNA, cytomegalovirus (CMV) DNA, and enterovirus RNA. Serologic studies for viral infection were done in 46 cases and, in 31, maternal stool samples were examined for enterovirus. The incidence of IUFD during the study period was 0.52%. Viral DNA was identified in 1 or more tissue samples in 6 cases. Parvovirus B19 DNA was found in the placenta in 2 cases, and also in fetal blood and amniotic fluid that were available in 1 of these cases. In the other, immunohistochemical analysis confirmed the diagnosis. CMV-DNA was present in the placenta but not in fetal blood in 1 case and in fetal blood but not the placenta in 2 cases. In 1 case, enterovirus RNA was present in amniotic fluid. All 31 attempts to isolate enterovirus from maternal stool samples were negative. Seroconversion for parvovirus B19 was documented only in the 2 DNA-positive cases. In no mother were there signs of primary infection by herpes simplex, rubella or Toxoplasma gondii. Maternal immunoglobulin G but no IgM or increase in IgG activity was found in the 3 CMV-DNA-positive cases. None of the women having an IUFD associated with viral infection had clinical signs of infection during pregnancy. No other obvious cause of IUFD was found in the women with documented infection. All 53 placental biopsies from normal term pregnancies were PCR-negative for parvovirus B19, CMV, and enterovirus. The investigators recommend that PCR studies of placental and/or fetal tissue for parvovirus B19, CMV, and enterovirus be included in the routine analysis of fetal deaths.