Maternal Seropositivity for Cytomegalovirus with Severe Foetal Hydrops: Foetal Analysis Focusing on Cerebral Changes

Abstract

Congenital cytomegalovirus (CMV) infection may give rise to severe foetal damage: 40–50% of infants born to mothers with primary CMV infection become congenitally infected and of these 5–18% are symptomatic with a 30% mortality rate. Around 80% of surviving infants present central nervous system sequelae such as microcephaly, microgyria, impaired neuronal migration, retarded growth, visual impairment and deafness 1. Foetal infection may result from material primary infection, recurrent infection or reactivation of a latent infection. The earlier transmission of CMV to the foetus occurs in pregnancy, the worse the prognosis, and primary infection always gives rise to more severe damage than secondary infection 2. A 29-year-old woman, para 0, presented at the 21st week of pregnancy with positive CMV IgG and IgM antibody titres disclosed at the 11th week of gestation, indicating viral reactivation. In addition, CMV-DNA had been detected in the amniotic fluid at the 20th week showing foetal infection. Ultrasound disclosed severe foetal hydrops and the patient had an MR scan. After termination of pregnancy and autopsy on the foetus, all tissues were examined histologically. After fixation in a formaldehyde-acetic acid mixture, the brain was scanned again by MR and then sectioned along the coronal plane for histological analysis. Microscopic virus-induced cytopathic changes were evident in many organs. In addition the brain showed features of delayed neuronal migration due to underdevelopment of the gyri and a thicker germinal matrix than in brains of the same gestational age, changes in migration lines already noted in the nuclear MR scan, and a cortex with few neuronal cells. CMV infection, demonstrated by typical viral inclusions, is seldom encountered, especially in forms with multiorgan viral inclusions. Brain NMR proved particularly useful in identifying the findings not disclosed by routine ultrasound during pregnancy and subsequently confirmed at histology. A multidisciplinary approach comprising clinical, radiological and pathological skills is essential for the purposes of diagnosis and genetic analysis.