Retrospective diagnosis of congenital cytomegalovirus infection and cortical maldevelopment

Abstract

Congenital cytomegalovirus (CMV) infection can cause malformations of cortical development (MCD). It is difficult to establish CMV as a cause of MCD several months postpartum. This can now be done by detection of CMV DNA in dried blood spots (DBS test) on Guthrie cards. The authors used DBS tests to assess 10 patients with MCD of unknown cause. Four of the 10 patients were positive for CMV.

Diagnosis of Human Congenital Cytomegalovirus Infection by Amplification of Viral DNA from Dried Blood Spots on Perinatal Cards

“…Several groups of investigators have used conventional PCR to amplify HCMV DNA extracted from blood spots on perinatal cards. 4 -7,10 -14 The most recent studies 7,14 used the method of Barbi and colleagues, 4 which involves heat extraction followed by a nested PCR reaction amplifying the HCMV glycoprotein B (gB) gene and detection by agarose gel electrophoresis. This method was 100% sensitive and 99% specific compared with viral culture in 509 babies with congenital HCMV infection defined by culture.…”

“…Congenital HCMV infection also causes other neurological sequelae such as microcephaly, seizures, mental retardation, paresis, and paralysis. Zucca and colleagues 7 recently retrospectively diagnosed congenital HCMV infection in 4 of 10 patients with malformations of cortical development by detecting HCMV DNA in dried blood spots. Our new assay provides a useful tool for similar retrospective clinical studies.…”

“…Conventional end-point polymerase chain reaction (PCR) has been used to amplify HCMV DNA from perinatal cards of children with sensorineural hearing loss 4,5 and malformations of cortical development. 6,7 Newborn blood is routinely collected and dried on perinatal cards as part of state newborn screening programs. When residual blood cards are retained and made available for clinical use, it provides new avenues for HCMV detection.…”

Prevalence of Congenital Cytomegalovirus Infection Assessed Through Viral Genome Detection in Dried Blood Spots in Children with Autism Spectrum Disorders

“…CMV-DNA detection on DBS has been widely used in the retrospective diagnosis of congenital infection when no neonatal sample was available (50,51). This test has also been used to evaluate the prevalence of congenital CMV infection in children with cortical development disorders (such as pachigiria and leucodystrophy of unknown origin) (52). The same test revealed that 20-30% of all cases of infantile deafness were due to congenital CMV infection (53,54).…”

Evaluation of Cytomegalovirus (CMV) DNA Quantification in Dried Blood Spots: Retrospective Study of CMV Congenital Infection

“…Policies for screening during pregnancy and at birth have not been implemented in European countries or in the United States, essentially because there is no well-established treatment for pregnant women or for newborns with CMV infection (7). Retrospective diagnosis of congenital infection has been achieved by PCR detection of the CMV DNA in dried blood spots (DBS) stored on perinatal Guthrie cards (2,5,6,8,9,14,16,17). Only one protocol (heat DNA extraction, followed by nested PCR) has been extensively evaluated in a clinical setting, with excellent sensitivity and specificity compared to that of viral isolation in the urine (1,2).…”