Original articleAsymptomatic congenital cytomegalovirus infection with neurological sequelae: A retrospective study using umbilical cord
Introduction
Congenital cytomegalovirus (CMV) infection represents a common cause of intrauterine infection [1], [2], [3] and is a major cause of neurological sequelae [4], [5]. There are two categories of congenital CMV infection—symptomatic and asymptomatic—that are generally based on the presence of clinical findings that suggest congenital infection at birth. Common physical and laboratory findings of symptomatic infants include petechial rash, jaundice, hepatosplenomegaly, microcephaly, elevated aspartate aminotransferase, hyperbilirubinemia and thrombocytopenia [6]. Approximately 90% of infants with congenital CMV infection are asymptomatic [7]. This categorization is clinically useful because infants with symptomatic infection are at a much higher risk for neurological sequelae than asymptomatic infants. Most (60–90%) symptomatic and 10–15% of asymptomatic congenital CMV infection patients develop one or more long-term neurological sequelae, such as intellectual disability [8] and sensorineural hearing loss [2], [9]. Several prospective screening studies have shown that symptomatic infants generally show mild symptoms during the neonatal period [5], [10]. Therefore, congenital CMV infection could easily be overlooked during the early infantile period.
More than two-thirds of patients with symptomatic congenital CMV infection exhibit various neuroimaging abnormalities, such as intracranial (especially periventricular) calcifications, cortical dysplasia, periventricular cysts (especially anterior temporal) and a parietal dominant white matter (WM) abnormality [11]. However, few previous studies have assessed brain imaging abnormalities in asymptomatic cases with neurological sequelae because retrospective diagnosis is difficult beyond the neonatal period.
A recent study reported that intellectual disability in 5 of 20 patients was caused by congenital CMV infections, which were retrospectively diagnosed using umbilical cords [12]. To determine the clinical characteristics of asymptomatic congenital CMV infection associated with neurological sequelae, we performed retrospective diagnoses of congenital CMV infections using preserved dried umbilical cord tissues and investigated the associated clinical and neuroimaging findings.
Section snippets
Data collection
This study was performed retrospectively between January 2005 and December 2013. Samples and data were collected from patients from all regions of Japan with possible congenital CMV infection who showed neurological symptoms such as intellectual disability, hearing impairment, cerebral palsy, microcephaly, and epilepsy. The lead author (MU) announced the enrollment of patients through the website of The Japanese Society of Child Neurology and the mailing list of the Annual Zao Conference on
Clinical characteristics of enrolled patients
We enrolled 191 patients who exhibited neurological symptoms (including intellectual disability, hearing impairment, cerebral palsy, epilepsy, and microcephaly) and/or brain imaging abnormalities (e.g., intracranial calcification and white matter abnormalities detected by CT and/or cortical dysplasia detected by MRI). A total of nine patients with symptomatic CMV infection (clinical symptoms such as petechiae, hepatosplenomegaly, and thrombocytopenia along with CMV identification near the
Discussion
In this study, we aimed to retrospectively investigate aspects of asymptomatic congenital CMV infection. Most enrolled congenital CMV patients with neurological sequelae had intellectual disabilities, which occurred more frequently than indicated in previous reports of low incidences (symptomatic: >50%, asymptomatic: 5–25%) [6], [10], [12], [19], [20]. From another point of view, 51 of 127 (40.2%) patients with intellectual disabilities were CMV-positive. Our result is more frequent but not
Acknowledgements
We are grateful to Ms. Yoko Chiba and Ms. Kumi Ito for their technical assistance of quantitative PCR analysis. We are also grateful for support of our research by the Japanese Society of Child Neurology.
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