The Limitations of Cytomegalovirus DNA Detection in Cerebrospinal Fluid of Newborn Infants With Congenital CMV Infection: A Tertiary Care Neonatal Center Experience

Abstract

Background: Congenital cytomegalovirus (cCMV) infection of the central nervous system (CNS) can cause ventriculomegaly, gliosis, calcifications and cortical defects. Detection of CMV DNA in cerebrospinal fluid by PCR (CSF-CMV-PCR) is a marker of CNS involvement. Objective: To evaluate a diagnostic value of the positive CSF-CMV-PCR in cCMV. Methods: Analysis of clinical, laboratory, neuroimaging and single-nucleotide polymorphisms (SNPs) data according to the results of CSF-CMV-PCR were performed in infants with cCMV. Results: A total of 168 infants were included; 145 (86.3%) had negative and 23 (13.7%) had positive CSF-CMV-PCR results. Associations between the positive CSF-CMV-PCR results and prematurity (odds ratio [OR] = 3.24; 95% confidence interval [CI]: 1.30–8.07), microcephaly (OR = 5.67; 95% CI: 2.08–15.41), seizures (OR = 4.15; 95% CI: 1.10–15.67), sensorineural hearing loss (OR = 6.6; 95% CI: 2.49–17.46), splenomegaly (OR = 8.13; 95% CI: 3.12–21.16), hepatitis (OR = 10.51; 95% CI: 3.31–33.35), petechiae (OR = 10.21; 95% CI: 3.78–27.57) and heterozygous T/C genotype at TLR4rs4986791 (OR = 7.88; 95% CI: 1.55–40.12) were observed. When using a multivariate logistic regression analysis, only the presence of severe sensorineural hearing loss (OR = 7.18; 95% CI: 1.75–29.34, P = 0.006), cystic lesions on MRI (OR 5.29; 95% CI: 1.31–21.36, P = 0.02), and calcifications on MRI (OR = 7.19; 95% CI: 1.67–30.97, P = 0.008) remained as the significant independent predictors of the positive CSF-CMV-PCR results. Conclusions: The detection of CMV DNA in CSF is associated with a higher rate of CNS damage including abnormal MRI neuroimaging and severe hearing loss. Therefore, detection of CMV DNA in CSF may be considered as a marker of severe CNS injury in cCMV infection. However, the very low prevalence of the positive CSF-CMV-PCR results, even in infants with proven CNS involvement, may imply its limited role in clinical practice.

Single Nucleotide Polymorphisms of Interleukins and Toll-like Receptors and Neuroimaging Results in Newborns with Congenital HCMV Infection

“…We found no association between the examined SNPs at the TLR4 and TLR9 genes and the neuroimaging results, although we previously documented that infants carrying the heterozygous C/T genotype at TLR4 rs4986791 had significantly increased odds of CMV-DNA detection in cerebrospinal fluid by more than seven times [66]. Interestingly, when using a multivariate logistic regression analysis, cystic lesions and calcifications on MRI were independent predictors of the positive CMV-PCR results in cerebrospinal fluid [66]. It might be speculated that SNPs of TLR4 have an impact of prolonged presence of CMV-DNA in cerebrospinal fluid and CNS damage in cCMV.…”

“…Individuals with SNP at TLR4 896 A/G (rs4986790) and TLR9 1174 G/A (rs352139) had a higher risk of the infectious mononucleosis and clinical outcomes when compared with subjects with the wild-type genotype [65]. We found no association between the examined SNPs at the TLR4 and TLR9 genes and the neuroimaging results, although we previously documented that infants carrying the heterozygous C/T genotype at TLR4 rs4986791 had significantly increased odds of CMV-DNA detection in cerebrospinal fluid by more than seven times [66]. Interestingly, when using a multivariate logistic regression analysis, cystic lesions and calcifications on MRI were independent predictors of the positive CMV-PCR results in cerebrospinal fluid [66].…”

Vertikale CMV-Transmission

“…Es wurden jeweils 136 74 bzw. 168 23 Neugeborene mit cCMV-Infektion auf die Präsenz von CMV-DNA im Liquor untersucht. Dabei zeigte sich eine ähnliche Rate positiver Liquorbefunde mit 15,4 % 74 bzw.…”

“…Dabei zeigte sich eine ähnliche Rate positiver Liquorbefunde mit 15,4 % 74 bzw. 13,7 % 23 . Ein positiver Nachweis von CMV-DNA im Liquor war assoziiert mit symptomatischer cCMV-Infektion und SNHL bei Geburt, stand jedoch nicht im Kontext zur VL im Blut, zum Neuroimaging oder outcome nach 6 Monaten 74 .…”

“…Ein positiver Nachweis von CMV-DNA im Liquor war assoziiert mit symptomatischer cCMV-Infektion und SNHL bei Geburt, stand jedoch nicht im Kontext zur VL im Blut, zum Neuroimaging oder outcome nach 6 Monaten [74]. Abweichend hierzu fanden Czech-Kowalska et al [23], dass ein positiver CMV-DNA-Nachweis im Liquor mit abnormalen MRI und schwerem Hörverlust korreliert. Es gibt bislang keine Evidenz, dass in der Routinediagnostik eine LP zur Klärung der Therapieindikation beiträgt [24].…”