Elsevier

The Journal of Pediatrics

Volume 163, Issue 3, September 2013, Pages 828-834.e1
The Journal of Pediatrics

Original Article
Clinical, Biochemical, and Neuroimaging Findings Predict Long-Term Neurodevelopmental Outcome in Symptomatic Congenital Cytomegalovirus Infection

Portions of this study were presented at the Spanish Congress of Neonatology and Perinatal Medicine, Oviedo, Spain, October 5-7, 2011, and Annual Scientific Meeting of the European Society for Pediatric Research, Newcastle, United Kingdom, October 14-17 2011.
https://doi.org/10.1016/j.jpeds.2013.03.014Get rights and content

Objective

To evaluate clinical, biochemical, and neuroimaging findings as predictors of neurodevelopmental outcome in patients with symptomatic congenital cytomegalovirus (CMV).

Study design

The study cohort comprised 26 patients with symptomatic congenital CMV born between 1993 and 2009 in a single center. Absolute and weight deficit–adjusted head circumference were considered. Cerebrospinal fluid (CSF) investigations included standard cytochemical analysis, determination of beta2-microglobulin (β2-m), neuron-specific enolase, and CMV DNA detection. Neuroimaging was classified according to a validated scoring system comprising calcifications, ventriculomegaly, and atrophy, with findings graded from 0 to 3. Systematic long-term neurodevelopmental assessment included motor function, cognition, behavior, hearing, vision, and epilepsy. Sequelae were graded as mild/absent, moderate, or severe; adverse outcome was defined as death or moderate to severe disability.

Results

Three children died. The mean age at follow-up of the survivors was 8.7 ± 5.3 years (range, 19 months to 18.0 years). Neonatal findings showing a significant association with adverse outcome were relative microcephaly, CSF β2-m concentrations, and grade 2-3 neuroimaging abnormalities (P < .05). Receiver operator characteristic curve analysis indicated that the most accurate single factor for predicting unfavorable outcome was CSF β2-m >7.9 mg/L (area under the curve, 0.84 ± 0.08; sensitivity, 69%; specificity, 100%). The combination of CSF β2-m >7.9 mg/L and moderate-severe neuroimaging alterations improved predictive ability (area under the curve, 0.92 ± 0.06; sensitivity, 87%; specificity, 100%).

Conclusion

Adjusted head circumference, CSF β2-m level, and neuroimaging studies have prognostic significance for neurodevelopmental outcome in newborns with congenital CMV. A combination of early findings improves the predictive value.

Section snippets

Methods

The study cohort comprised all newborns with a symptomatic congenital CMV infection who were admitted to La Paz Hospital, a university tertiary hospital located in Madrid, Spain, between 1993 and 2009, including the patients in our previous cohort.21 Patients with a major malformation, genetic or chromosomal syndrome, other congenital infection, or a CNS-significant disease not related to CMV were excluded. Patients born between 1993 and 2000 were identified retrospectively by reviewing the

Results

A total of 29 infants with symptomatic congenital CMV infection were identified, 3 of whom were excluded from our analysis (2 with a major malformation and 1 with a chromosomal syndrome). Of the remaining 26 patients, 15 were born after 2000 and were included prospectively. Important demographic, perinatal, and clinical characteristics of the study patients are presented in Table I. Seventeen patients (65%) received ganciclovir therapy, including 15 of 20 patients with CNS involvement33, 34

Discussion

Our results demonstrate that relative microcephaly, elevated CSF protein and β2-m levels, and moderate-severe neuroimaging abnormalities are neonatal predictors of adverse neurologic and developmental outcomes for symptomatic congenital CMV infection. The presence of high CSF β2-m concentrations at birth appears to be the best independent biomarker of moderate-severe adverse prognosis. Moreover, analysis of both CSF β2-m and HC or especially neuroimaging findings provides better predictive

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  • Cited by (0)

    Partially supported by Roche Spain, which was not involved in the study design; the collection, analysis and interpretation of data; the writing of the manuscript; or the decision to submit the manuscript for publication. The authors declare no conflicts of interest.

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