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Background. Human cytomegalovirus (HCMV) is a major cause of congenital infection as well as sensorineural hearing loss and neurodevelopmental delay. Prenatal diagnosis is based mainly on the detection of HCMV infection in amniotic fluid and on ultrasound (US) examination. The major limitation of these techniques is that US identifies prenatally only up to 15-20% of infected babies and positive results of amniotic fluids tests do not discriminate between the infants who will have symptoms at birth and those who will not. Objectives. The aims of this study are to evaluate the usefulness of fetal cerebral magnetic resonance (MR) and biological parameters in fetal blood when a high HCMV load is detected in amniotic fluid. The results of MR and fetal blood testing were correlated with the fetal histological examination or neonatal outcome. Methods. We enrolled 17 women at 20-21 weeks gestation with documented intrauterine transmission of HCMV (amniotic fluid with a viral load more than 10^5 copies/ml) with or without abnormal ultrasound findings. All pregnant women performed cerebral MR at 21 weeks gestation. Twelve women elected to terminate the pregnancy and fetal blood was collected from the umbilical cord. Immunological, haematological, biochemical and virological examinations were performed in fetal blood. HCMV antigen expression and inflammatory response were studied in all fetal tissues including inner ears using immunohistochemical staining procedures. Five pregnancies continued up to term and fetal MR was repeated at 32 weeks of gestation. Results. We found no evidence of brain HCMV infection by immunohistochemistry in 4 out of 12 foetuses and US and MR brain imaging were both normal in these cases. Eight fetal brains were HCMV positive and a brain histological damage was observed. Among these, 4 HCMV positive inner ears were observed. Viral infection always involved the stria vascularis, the most vascularised area of the cochlea, and less the Reissner's membrane, the Organ of Corti and the vestibular apparatus. Considering the 8 fetuses with histological brain damage, US was pathological in 4 cases (50%) and MR imaging only in 3 (38%). The most prevalent finding were periventricular hyperechogenicity (US) and microcephaly (MR). In fetal blood only platelet count and the % of natural killer cells were associated significantly .

Background: Cytomegalovirus (CMV) is the major infectious cause of congenital abnormalities in the central nervous system due to intrauterine infection in humans. Design and population: Twenty-seven fetuses with congenital CMV infection documented at 20–21 weeks' gestation by invasive prenatal diagnosis (amniotic fluid culture and PCR positive with a viral load > 10 5 copies/ml) underwent histological examination. We focused our attention on brain and placenta to understand the histopathogenesis of cerebral damage and to find a possible correlation between placental infection and ischemic brain damage. Material and methods: Fetal sections were studied with haematoxylin and eosin staining, immunohistochemistry for CMV early (ppUL44) and leukocyte common antigen CD45 to detect the inflammatory cells. Results: CMV-positivity was detected in all placentas and 55% (15/27) of brains. Six out of 15 CMV-positive brains showed mild inflammatory response without necrosis and only mild telencephalic leukencephalopathy. Four out of 15 CMV-positive brains showed a moderate CD45-positive inflammatory response associated with focal microglial nodules and telencephalic leukencephalopathy. The CD45-positive inflammatory response in the remaining five of the 15 CMV-positive brains was severe and associated with diffuse cerebral damage such as cortical necrosis, polymicrogyria and periventricular leukomalacia. No damage was observed in CMV-negative brains. Conclusions: Diffuse chronic villitis with necrosis was found in all the placentas of fetuses with severe brain damage. In other placentas, chronic villitis and necrosis were only focal. Brain damage may be caused not only by CMV infection but also by inflammatory infiltration and hypoxia due to severe placentitis.