Cytomegalovirus (CMV) is the most common congenital viral infection, with birth prevalence ranging from 0.5 to 2%. Congenital CMV (cCMV) is the main nongenetic cause of congenital sensorineural hearing loss and neurological damage. The rate of vertical transmission in primary infection ranges from 30% to 65% if the maternal CMV-seroconversion occurs during the third trimester of pregnancy, and the risk of long-term sequelae is up to 58% in infected children.
cCMV can be suspected in case of mother presenting symptoms, or in case of abnormal ultrasound (US) findings. The detection of CMV DNA in the amniotic fluid is considered the gold standard for the diagnosis of fetal infection, combined with ultrasound assessment, which is useful to evaluate the fetal involvement by detecting cerebral and extracerebral findings suggestive of congenital CMV.
A normal ultrasound examination is reassuring but does not completely exclude the possibility of an infected fetus, symptomatic neonate, or development of long-term neurologic morbidity. Magnetic resonance imaging (MRI) may provide additional information about anomalies, particularly neurologic abnormalities, in infected fetuses with normal ultrasound. The primary aim of this study is to evaluate the role of fetal MRI in detecting anomalies in fetuses with CMV infection and normal US examination; the secondary aim is to determine the optimal gestational age for performing MRI in fetuses affected by such infections. Parental counselling should be improved with a better knowledge of the real predictive value of MRI and US imaging findings in studying the fetal outcome.
Congenital CMV still remains an underdiagnosed condition, partially due to the absence of systematic screening but also due to unrecognized prenatal findings suspicious for CMV infection. Accurate and timely diagnosis becomes paramount, as well as identification of fetuses at risk for neurodevelopmental sequelae. This raises the importance of amniotic fluid or newborn testing, allowing fetal treatment in selected cases and avoiding uncertain diagnosis for children with cCMV born with nonspecific symptoms (mean specificity of neonatal symptoms: 12%) or delayed symptoms.
At the same time, imaging in congenital CMV (cCMV) has two main objectives: detection of fetal structural anomalies for correct diagnosis and provision of prognostic information. Therefore, imaging takes a prominent role in prenatal diagnosis of cCMV.
Prenatal imaging in cCMV is primarily focused on the brain, given the neurotropism of the virus that may infect several cell types, including neurons, astrocytes, radial glia and endothelial cells, and may result in a number of insults to neuronal proliferation, migration, and cortical cell organization.
Detection of cCMV related central nervous system (CNS) anomalies is a predictor of poor outcome among infected fetuses, while a normal neurosonographic examination performed by expert sonographers is a good predictor of normal neurodevelopmental outcome.
Still, some fetuses deemed normal on prenatal imaging are symptomatic at birth or develop delayed cCMV¿associated symptoms. Advanced MR sequences may help in this field and in determining prognosis, but further studies are needed.
Up to date, while US is the method of choice for fetal imaging, MRI has an established added value in the detection of fetal brain anomalies in several conditions and has a growing potential for the evaluation of structural but also functional as well as metabolic imaging methods. Furthermore, MRI has also been used in multiple studies concerning CMV, with a high negative predictive value (96.8%-99%) for neurological impairment and SNHL.
MRI findings in cCMV are often unspecific, with ventriculomegaly and white matter (WM) signal abnormalities being the most commonly described anomalies of the central nervous system (CNS). More characteristic, but less frequently observed, features include temporal lobe lesions (abnormal WM, cysts, and enlargement of the temporal horns), ventriculitis and intracranial calcification. Depending on the timing of infection and injury extent, a wide spectrum of abnormalities can be seen. cCMV affects the germinal matrix, leading to neuronal cell loss and diffuse disruptions of migration when the insult occurs before 16-18 weeks of gestation. (Micro)lissencephaly and polymicrogyria can be seen in injuries that occur between 18 and 24 weeks, whereas fetuses affected in the third trimester usually have a normal gyral pattern.
Anterior temporal lobe lesions are the most specific MRI finding, and in these cases, MRI may add information to US. Other unspecific findings could raise the suspicion of fetal infection, particularly when multiple sites are involved. This highlights the need for a full fetal assessment, as these findings may be outside the CNS. Advanced MR sequences may help in determining prognosis, but further studies are needed to assess their significance.