Abstract
BackgroundNeonatal hypoxic-ischemic encephalopathy (HIE) commonly leads to neurodevelopmental impairment, raising the need for prognostic tools which may guide future therapies in time. Prognostic value of proton MR spectroscopy (H-MRS) between 1 and 46 days of age has been extensively studied; however, the reproducibility and generalizability of these methods are controversial in a general clinical setting. Therefore, we investigated the prognostic performance of conventional H-MRS during first 96 postnatal hours in hypothermia-treated asphyxiated neonates.MethodsFifty-one consecutive hypothermia-treated HIE neonates were examined by H-MRS at three echo-times (TE = 35, 144, 288 ms) between 6 and 96 h of age, depending on clinical stability. Patients were divided into favorable (n = 35) and unfavorable (n = 16) outcome groups based on psychomotor and mental developmental index (PDI and MDI, Bayley Scales of Infant Development II) scores (≥ 70 versus < 70 or death, respectively), assessed at 18–26 months of age. Associations between 36 routinely measured metabolite ratios and outcome were studied. Age-dependency of metabolite ratios in whole patient population was assessed. Prognostic performance of metabolite ratios was evaluated by Receiver Operating Characteristics (ROC) analysis.ResultsThree metabolite ratios showed significant difference between outcome groups after correction for multiple testing (p < 0.0014): myo-inositol (mIns)/N-acetyl-aspartate (NAA) height, mIns/creatine (Cr) height, both at TE = 35 ms, and NAA/Cr height at TE = 144 ms. Assessment of age-dependency showed that all 3 metabolite ratios (mIns/NAA, NAA/Cr and mIns/Cr) stayed constant during first 96 postnatal hours, rendering them optimal for prediction. ROC analysis revealed that mIns/NAA gives better prediction for outcome than NAA/Cr and mIns/Cr with cut-off values 0.6798 0.6274 and 0.7798, respectively, (AUC 0.9084, 0.8396 and 0.8462, respectively, p < 0.00001); mIns/NAA had the highest specificity (95.24%) and sensitivity (84.62%) for predicting outcome of neonates with HIE any time during the first 96 postnatal hours.ConclusionsOur findings suggest that during first 96 h of age even conventional H-MRS could be a useful prognostic tool in predicting the outcome of asphyxiated neonates; mIns/NAA was found to be the best and age-independent predictor.
Highlights
Neonatal hypoxic-ischemic encephalopathy (HIE) commonly leads to neurodevelopmental impairment, raising the need for prognostic tools which may guide future therapies in time
Of the 51 patients, 16 infants were considered to have poor outcome, including the 9 patients that died in the perinatal period, and the 7 patients who had moderately/severely delayed development (Mental Developmental Index (MDI) or Psychomotor Developmental Index (PDI) < 70)
Even though further studies are needed to outline the hypothermia-induced changes in metabolites detected by Proton magnetic resonance spectroscopy (H-MRS), these findings suggest that thalamic myo-inositol/N-acetyl-aspartate values are not affected by cooling
Summary
Neonatal hypoxic-ischemic encephalopathy (HIE) commonly leads to neurodevelopmental impairment, raising the need for prognostic tools which may guide future therapies in time. Perinatal asphyxia and consequential hypoxic-ischemic encephalopathy (HIE) remains one of the leading causes of perinatal brain injury, affecting more than two million neonates yearly worldwide [1]. Therapeutic hypothermia is the one and only neuroprotective method proven effective to reduce mortality and long-term morbidity in HIE [3]. The key to successful neuroprotection is the earliest possible initiation regardless of the therapy chosen [6]. This in turn requires proper and timely diagnosis and early establishment of prognosis [7]
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