Abstract
BackgroundIdentification of early signs of hypoxic ischemic encephalopathy (HIE) with magnetic resonance imaging (MRI) has proven of prognostic significance. Yet, the importance of intracranial hemorrhage (ICH), being present concomitantly had not been investigated yet, despite the known influence of hypothermia on hemostasis. We aimed to determine whether presence of ICH on MRI alongside the signs of HIE have an impact on prognosis in neonates with the clinical diagnosis of HIE.MethodsA retrospective study of consecutively sampled 108 asphyxiated term infants admitted to a tertiary neonatal intensive care unit (between 2007 and 2016), treated with whole body hypothermia and having brain MRI within 1 week of life was conducted. Presence or absence of HIE signs on MRI (basal ganglia-thalamus, watershed pattern and total brain injury) and on MR spectroscopy (lactate peak with decreased normal metabolites measured by Lac/NAA ratio) and/or of the five major types of ICH were recorded. Neurodevelopmental outcome was measured with Bayley Scales of Infant Development-II (BSID-II) test. Death or abnormal neurodevelopment (BSID-II score < 85) was defined as poor outcome in Chi-square test. Multivariate logistic regression analysis was performed on survivors.ResultsMRI and MR-spectroscopy (MRS) signs of HIE were present in 72% (n = 78). 36% (n = 39) of neonates had ICH, being mainly small in size. Chi-square test showed a relationship between neurodevelopmental outcome and initial MRI. Unadjusted logistic regression showed that neonates presenting MRI and MRS signs of HIE have 6.23 times higher odds for delayed mental development (OR = 6.2292; CI95% = [1.2642; 30.6934], p = 0.0246), than infants without imaging alterations; with no ICH effect on outcome. Adjustment for clinical and imaging parameters did not change the pattern of results, i.e. HIE remained an independent risk factor for delayed neurodevelopment (OR = 6.2496; CI95% = [1.2018; 32.4983], p = 0.0294), while ICH remained to have no significant effect.ConclusionHIE related MRI abnormalities proved to be important prognostic factors of poor outcome in cooled asphyxiated infants when present, suggesting that early MRI with MRS is beneficial for prognostication. Interestingly, ICHs present in about one third of all cases had no significant effect on neurodevelopmental outcome, despite the known hemostasis altering effects of hypothermia.
Highlights
Identification of early signs of hypoxic ischemic encephalopathy (HIE) with magnetic resonance imaging (MRI) has proven of prognostic significance
In this retrospective observational study of cooled infants with the clinical diagnosis of HIE, we aimed to investigate whether the coexistence of intracranial hemorrhage (ICH) on early MRI with the imaging signs of HIE have an impact on the prognosis
As the aim of our study was to investigate ICH present during or early after hypothermia treatment and detect diffusion and spectral changes of HIE known to have a temporal evolution we only considered brain MRI performed during the first week after birth
Summary
Identification of early signs of hypoxic ischemic encephalopathy (HIE) with magnetic resonance imaging (MRI) has proven of prognostic significance. The results of the Infant Cooling Evaluation Collaboration (ICE) trial, a multicenter, international, randomized controlled trial shown the reduction of the risk of death and major sensorineural disability at 2 years of age and concluded that whole-body hypothermia is a safe and effective neuroprotective method with minimal adverse effects [6, 7]. The different types of ICHs visible on MRI in asphyxiated neonates, were not considered in the previous studies, they may be of additional impact on the long term outcome of neonatal HIE, as they may carry a potential risk of intracranial complication when hypothermic treatment is adopted [9]. The many previous studies emphasizing the prognostic effect of signal abnormalities on conventional sequences, diffusion restriction pattern, and brain MRS either analyzed a relatively small sample size or MRS was performed after the first week of life or was not involved in the evaluation, meaning that those HIE positive infants having only spectroscopic abnormality were not involved in the study population [13, 15, 25,26,27]
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