title: Congenital cytomegalovirus infection: patterns of fetal brain damage.
abstract: Cytomegalovirus (CMV) is the most prevalent infectious agent causing neurological dysfunction in the developing brain. This study analysed the different patterns of tissue damage, particularly in the brain, of fetuses with documented CMV infection. We studied 45 fetuses at 20-21 weeks of gestation with congenital CMV infection documented by invasive positive prenatal diagnosis. At the time of amniocentesis, abnormal ultrasound findings had been recorded for 13 of the 45 fetuses (29%). Histological and immunohistochemical characterization was performed on the placenta, brain, heart, lung, liver, kidney, and pancreas. The different degrees of brain damage were correlated with tissue viral load, inflammatory response, placental functionality, and extramedullary haematopoiesis. Even though a high CMV load was detected in all amniotic fluids, brain infection occurred in only 62% of the fetuses and with different degrees of severity. Tissues with a low viral load showed a globally weak inflammatory response, and fetuses had only mild brain damage, whereas tissues with a high CMV load showed prominent infiltration of the activated cytotoxic CD8(+) T-lymphocytes responsible for immune-mediated damage. Furthermore, severe placental infection was associated with diffuse villitis and necrosis, consistent with functional impairment and possible consequent hypoxic cerebral damage. Brain injury induced by CMV congenital infection may be the result of uncontrolled viral replication, immune-mediated damage by cytotoxic CD8(+) T-lymphocytes, and, in the presence of placental insufficiency, fetal hypoxia.
authors.affiliation: Operative Unit of Clinical Microbiology, St Orsola-Malpighi University Hospital, Bologna, Italy. liliana.gabrielli@aosp.bo.it
authors.forename: L
authors.initials: L
authors.lastname: Gabrielli
authors.forename: M P
authors.initials: MP
authors.lastname: Bonasoni
authors.forename: D
authors.initials: D
authors.lastname: Santini
authors.forename: G
authors.initials: G
authors.lastname: Piccirilli
authors.forename: A
authors.initials: A
authors.lastname: Chiereghin
authors.forename: E
authors.initials: E
authors.lastname: Petrisli
authors.forename: R
authors.initials: R
authors.lastname: Dolcetti
authors.forename: B
authors.initials: B
authors.lastname: Guerra
authors.forename: M
authors.initials: M
authors.lastname: Piccioli
authors.forename: M
authors.initials: M
authors.lastname: Lanari
authors.forename: M P
authors.initials: MP
authors.lastname: Landini
authors.forename: T
authors.initials: T
authors.lastname: Lazzarotto
mesh_terms: D001927:Brain Diseases / Q000151:congenital* / Q000473:pathology / Q000821:virology*; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000473:pathology; D003586:Cytomegalovirus Infections / Q000151:congenital* / Q000473:pathology*; D005260:Female; D005315:Fetal Diseases / Q000473:pathology / Q000821:virology*; D006411:Hematopoiesis, Extramedullary; D006651:Histocytochemistry; D006801:Humans; D010920:Placenta / Q000473:pathology / Q000821:virology; D010922:Placenta Diseases / Q000473:pathology / Q000821:virology; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000473:pathology / Q000821:virology*; D018709:Statistics, Nonparametric; D019562:Viral Load