Cerebral magnetic resonance biomarkers in neonatal encephalopathy: a meta-analysis.
OBJECTIVE
Accurate prediction of neurodevelopmental outcome in neonatal encephalopathy (NE) is important for clinical management and to evaluate neuroprotective therapies. We undertook a meta-analysis of the prognostic accuracy of cerebral magnetic resonance (MR) biomarkers in infants with neonatal encephalopathy.


METHODS
We reviewed all studies that compared an MR biomarker performed during the neonatal period with neurodevelopmental outcome at > or =1 year. We followed standard methods recommended by the Cochrane Diagnostic Accuracy Method group and used a random-effects model for meta-analysis. Summary receiver operating characteristic curves and forest plots of each MR biomarker were calculated. chi(2) tests examined heterogeneity.


RESULTS
Thirty-two studies (860 infants with NE) were included in the meta-analysis. For predicting adverse outcome, conventional MRI during the neonatal period (days 1-30) had a pooled sensitivity of 91% (95% confidence interval [CI]: 87%-94%) and specificity of 51% (95% CI: 45%-58%). Late MRI (days 8-30) had higher sensitivity but lower specificity than early MRI (days 1-7). Proton MR spectroscopy deep gray matter lactate/N-acetyl aspartate (Lac/NAA) peak-area ratio (days 1-30) had 82% overall pooled sensitivity (95% CI: 74%-89%) and 95% specificity (95% CI: 88%-99%). On common study analysis, Lac/NAA had better diagnostic accuracy than conventional MRI performed at any time during neonatal period. The discriminatory powers of the posterior limb of internal capsule sign and brain-water apparent diffusion coefficient were poor.


CONCLUSIONS
Deep gray matter Lac/NAA is the most accurate quantitative MR biomarker within the neonatal period for prediction of neurodevelopmental outcome after NE. Lac/NAA may be useful in early clinical management decisions and counseling parents and as a surrogate end point in clinical trials that evaluate novel neuroprotective therapies.
Thayyil
Sudhin
S
MBBS, MRCPCH, UCL Institute for Women's Health, Department of Neonatology, 86-96 Chenies Mews, London WC1E 6HX, England. s.thayyil@ucl.ac.uk
Chandrasekaran
Manigandan
M
Taylor
Andrew
A
Bainbridge
Alan
A
Cady
Ernest B
EB
Chong
W K Kling
WK
Murad
Shahed
S
Omar
Rumana Z
RZ
Robertson
Nicola J
NJ
D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000032:analysis; D001479:Basal Ganglia / Q000737:chemistry; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000175:diagnosis / Q000378:metabolism*; D007231:Infant, Newborn; D007773:Lactates / Q000032:analysis*; D009682:Magnetic Resonance Spectroscopy; D011379:Prognosis; D012372:ROC Curve; D012680:Sensitivity and Specificity
D007773:Lactates; D001224:Aspartic Acid; C000179:N-acetylaspartate