title: Clinical, biochemical, and neuroimaging findings predict long-term neurodevelopmental outcome in symptomatic congenital cytomegalovirus infection.
abstract: OBJECTIVE
  To evaluate clinical, biochemical, and neuroimaging findings as predictors of neurodevelopmental outcome in patients with symptomatic congenital cytomegalovirus (CMV).
  
  
  METHODS
  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%).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Neonatology, Sant Joan de Deu University Hospital, Barcelona, Spain. anaalarcon@hsjdbcn.org
authors.forename: Ana
authors.initials: A
authors.lastname: Alarcon
authors.forename: Miriam
authors.initials: M
authors.lastname: Martinez-Biarge
authors.forename: Fernando
authors.initials: F
authors.lastname: Cabañas
authors.forename: Angel
authors.initials: A
authors.lastname: Hernanz
authors.forename: Jose
authors.initials: J
authors.lastname: Quero
authors.forename: Alfredo
authors.initials: A
authors.lastname: Garcia-Alix
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000134:cerebrospinal fluid; D002648:Child; D002675:Child, Preschool; D003586:Cytomegalovirus Infections / Q000150:complications / Q000151:congenital / Q000175:diagnosis* / Q000401:mortality; D002658:Developmental Disabilities / Q000175:diagnosis / Q000821:virology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D016014:Linear Models; D016015:Logistic Models; D008297:Male; D009422:Nervous System Diseases / Q000175:diagnosis / Q000821:virology*; D059906:Neuroimaging; D009483:Neuropsychological Tests; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D012372:ROC Curve; D012189:Retrospective Studies
chemical_list: D015415:Biomarkers
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