Severe fetal symptomatic infection from human cytomegalovirus following non-primary maternal infection: report of two cases

Introduction Human cytomegalovirus (HCMV) is the most common congenital infection, expecially severe after a maternal primary infection; sequelae in neonates born to mothers experiencing a non-primary infection have been already reported. Hereby, two cases of severe fetal HCMV disease in seroimmune gravidas referred to our Unit are described. Cases presentation Case 1 A fetus at 21 weeks' gestation with signs of anemia and brain abnormalities at ultrasound (US), described at magnetic resonance (MR) imaging as ependymal irregularity and bilateral asymmetric parenchimal thinning; amniotic fluid sample was positive for HCMV although the woman had a previous immunity; after termination of pregnancy, autopsy demonstrated a thicken layer of disorganized neurons on the right cortical plate, while on the left there was a morphological pattern coherent with polymicrogyria. Case 2 A fetus at 20 weeks' gestation with anemia, moderate atrio-ventricular insufficiency, hepatosplenomegaly but no major cerebral lesions. Fetal blood was positive for HCMV, although unexpected for pre-pregnancy maternal immunity, and intrauterine transfusion was needed. A cesarean section at 34 weeks gestation was performed due to worsening condition of the fetus, who had a birthweight of 2210 grams, needed platelet transfusions but MR examination and clinical evaluation were normal. Conclusion The impact of non-primary maternal infection on pregnancy outcome is unknown and fetal brain damage in HCMV seroimmune transmitter-mothers can occur as a consequence of maternal re-infection or reactivation for a hypotetic different role of HCMV-primed CD4+ or CD8+ T-cells in fetal brain, with progressive brain lesions coexistent in the first case and with severe unexpected anemia in the second case. A previous maternal HCMV immunity should not exempt to test anemic fetuses for such infection, nor to consider a potential transplacental transmission.