Clinical, biochemical, and neuroimaging findings predict long-term neurodevelopmental outcome in symptomatic congenital cytomegalovirus infection

J Pediatr. 2013 Sep;163(3):828-34.e1. doi: 10.1016/j.jpeds.2013.03.014. Epub 2013 Apr 13.


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.

Keywords: BSID-III; Bayley Scales of Infant and Toddler Development, Third Edition; Beta(2)-microglobulin; CMV; CNS; CP; CSF; CT; Central nervous system; Cerebral palsy; Cerebrospinal fluid; Computed tomography; Cytomegalovirus; GMFCS; Gross Motor Function Classification System; HC; Head circumference; MRI; Magnetic resonance imaging; NSE; Neuron-specific enolase; PV; Periventricular; US; Ultrasonography; WBC; White blood cell; β(2)-m.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Biomarkers / cerebrospinal fluid
  • Child
  • Child, Preschool
  • Cytomegalovirus Infections / complications
  • Cytomegalovirus Infections / congenital
  • Cytomegalovirus Infections / diagnosis*
  • Cytomegalovirus Infections / mortality
  • Developmental Disabilities / diagnosis
  • Developmental Disabilities / virology*
  • Female
  • Follow-Up Studies
  • Humans
  • Infant
  • Infant, Newborn
  • Linear Models
  • Logistic Models
  • Male
  • Nervous System Diseases / diagnosis
  • Nervous System Diseases / virology*
  • Neuroimaging
  • Neuropsychological Tests
  • Predictive Value of Tests
  • Prognosis
  • Prospective Studies
  • ROC Curve
  • Retrospective Studies


  • Biomarkers