scholarly journals Therapeutic hypothermia initiated within 6 hours of birth is associated with reduced brain injury on MR biomarkers in mild hypoxic-ischaemic encephalopathy: a non-randomised cohort study

2018 ◽  
Vol 104 (5) ◽  
pp. F515-F520 ◽  
Author(s):  
Paolo Montaldo ◽  
Peter J Lally ◽  
Vânia Oliveira ◽  
Ravi Swamy ◽  
Josephine Mendoza ◽  
...  
Keyword(s):  
Cohort Study ◽  
White Matter ◽  
Therapeutic Hypothermia ◽  
Neuroprotective Effect ◽  
Neurodevelopmental Outcome ◽  
Adverse Outcomes ◽  
White Matter Injury ◽  
Whole Body ◽  
Neurodevelopmental Outcomes ◽  
The Usa

ObjectiveTo examine the effect of therapeutic hypothermia on MR biomarkers and neurodevelopmental outcomes in babies with mild hypoxic-ischaemic encephalopathy (HIE).DesignNon-randomised cohort study.SettingEight tertiary neonatal units in the UK and the USA.Patients47 babies with mild HIE on NICHD neurological examination performed within 6 hours after birth.InterventionsWhole-body cooling for 72 hours (n=32) or usual care (n=15; of these 5 were cooled for <12 hours).Main outcome measuresMRI and MR spectroscopy (MRS) within 2 weeks after birth, and a neurodevelopmental outcome assessment at 2 years.ResultsThe baseline characteristics in both groups were similar except for lower 10 min Apgar scores (p=0.02) in the cooled babies. Despite this, the mean (SD) thalamic NAA/Cr (1.4 (0.1) vs 1.6 (0.2); p<0.001) and NAA/Cho (0.67 (0.08) vs 0.89 (0.11); p<0.001) ratios from MRS were significantly higher in the cooled group. Cooled babies had lower white matter injury scores than non-cooled babies (p=0.02). Four (27%) non-cooled babies with mild HIE developed seizures after 6 hours of age, while none of the cooled babies developed seizures (p=0.008). Neurodevelopmental outcomes at 2 years were available in 40 (85%) of the babies. Adverse outcomes were seen in 2 (14.3%) non-cooled babies, and none of the cooled babies (p=0.09).ConclusionsTherapeutic hypothermia may have a neuroprotective effect in babies with mild HIE, as demonstrated by improved MRS biomarkers and reduced white matter injury on MRI. This may warrant further evaluation in adequately powered randomised controlled trials.

scholarly journals Correlation Between White Matter Injury Identified by Neonatal Diffusion Tensor Imaging and Neurodevelopmental Outcomes Following Term Neonatal Asphyxia and Therapeutic Hypothermia: An Exploratory Pilot Study

2019 ◽  
Vol 34 (10) ◽  
pp. 556-566 ◽  
Author(s):  
Gwendolyn J. Gerner ◽  
Eric I. Newman ◽  
V. Joanna Burton ◽  
Brenton Roman ◽  
Elizabeth A. Cristofalo ◽  
...  
Keyword(s):  
Diffusion Tensor Imaging ◽  
White Matter ◽  
Pilot Study ◽  
Therapeutic Hypothermia ◽  
Diffusion Tensor ◽  
White Matter Injury ◽  
Hypoxic Ischemic Encephalopathy ◽  
Group Differences ◽  
Neurodevelopmental Outcomes ◽  
Ischemic Encephalopathy

Aim: Hypoxic-ischemic encephalopathy is associated with damage to deep gray matter; however, white matter involvement has become recognized. This study explored differences between patients and clinical controls on diffusion tensor imaging, and relationships between diffusion tensor imaging and neurodevelopmental outcomes. Method: Diffusion tensor imaging was obtained for 31 neonates after hypoxic-ischemic encephalopathy treated with therapeutic hypothermia and 10 clinical controls. A subgroup of patients with hypoxic-ischemic encephalopathy (n = 14) had neurodevelopmental outcomes correlated with diffusion tensor imaging scalars. Results: Group differences in diffusion tensor imaging scalars were observed in the putamen, anterior and posterior centrum semiovale, and the splenium of the corpus callosum. Differences in these regions of interest were correlated with neurodevelopmental outcomes between ages 20 and 32 months. Conclusion: Therapeutic hypothermia may not be a complete intervention for hypoxic-ischemic encephalopathy, as neonatal white matter changes may continue to be evident, but further research is warranted. Patterns of white matter change on neonatal diffusion tensor imaging correlated with neurodevelopmental outcomes in this exploratory pilot study.

scholarly journals Influence of timing of initiation of therapeutic hypothermia on brain MRI and neurodevelopment at 18 months in infants with HIE: a retrospective cohort study

2019 ◽  
Vol 3 (1) ◽  
pp. e000442 ◽  
Author(s):  
Mireille Guillot ◽  
Marissa Philippe ◽  
Elka Miller ◽  
Jorge Davila ◽  
Nicholas James Barrowman ◽  
...  
Keyword(s):  
Cohort Study ◽  
Brain Injury ◽  
Therapeutic Hypothermia ◽  
Retrospective Cohort Study ◽  
Retrospective Cohort ◽  
Neonatal Intensive Care ◽  
Brain Mri ◽  
Whole Body ◽  
Neurodevelopmental Outcomes ◽  
Timing Of Initiation

ObjectiveTo examine the influence of timing of initiation of therapeutic hypothermia (TH) on brain injury on MRI and on neurodevelopmental outcomes at 18 months.DesignRetrospective cohort study.SettingTertiary neonatal intensive care unit in Ontario, Canada.PatientsNinety-one patients with hypoxic ischaemic encephalopathy (HIE) were included, 54 in the early TH group and 37 in the late TH group.InterventionWhole-body hypothermia administered for 72 hours, initiated either before 3 hours of life (early TH) or between 3 and 6 hours of life (late TH).Main outcome measuresBrain injury on MRI after TH (assessed by two neuroradiologists), and neurodevelopmental outcomes at 18 months old.ResultsTH was initiated at a median time of 1.4 hours (early TH) and 4.4 hours (late TH). Sixty-four neonates (early TH=36, late TH=28) survived and completed neurodevelopmental assessment at 18 months. Neonates in the early TH group received more extensive resuscitation than neonates in the late TH group (p=0.0008). No difference was observed between the two groups in the pattern or severity of brain injury on MRI, or in the neurodevelopmental outcomes at 18 months. The non-survivors (n=16) had lower Apgar scores at 10 min, more extensive resuscitation, suffered from more severe HIE and had significantly more abnormal cerebral function monitoring.ConclusionIn this retrospective cohort study, TH initiated early was associated neither with a difference in brain injury on MRI nor better neurodevelopmental outcomes at 18 months.

Clinical Findings and Neurologic Outcome in Neonatal Encephalopathy With White Matter Injury Accompanied by Rotavirus

2018 ◽  
Vol 33 (4) ◽  
pp. 297-305 ◽  
Author(s):  
Jae Kyun Ku ◽  
Young Jin Heo ◽  
Keun Soo Lee ◽  
Bo Lyun Lee
Keyword(s):  
White Matter ◽  
Neurodevelopmental Outcome ◽  
Clinical Findings ◽  
White Matter Injury ◽  
Periventricular White Matter ◽  
Neonatal Encephalopathy ◽  
Neurodevelopmental Outcomes ◽  
Laboratory Findings ◽  
Group I ◽  
Group Ii

Our objective was to elucidate the clinical characteristics and neurodevelopmental outcomes in neonatal encephalopathy with characteristic white matter injury as compared with other injury patterns on magnetic resonance diffusion-weighted imaging. We conducted a retrospective study comparing clinical and laboratory findings, and neurologic outcomes between 17 newborns with diffuse lesions in the periventricular white matter and white matter tract (group I) and 22 newborns with other patterns (group II). Stool samples indicated that 16 neonates (94.1%) in group I were rotavirus-positive, whereas none in group II had rotavirus infection. Significantly lower calcium levels were found in group I than in group II ( P < .001). Moreover, a more favorable neurodevelopmental outcome was observed in group I than in group II. This study suggests that characteristic white matter injury in neonatal encephalopathy may be related to decreased calcium levels induced by rotavirus, and may have a better neurodevelopmental prognosis than other causes.

scholarly journals Increased Use of Therapeutic Hypothermia in Infants with Milder Neonatal Encephalopathy due to Presumed Perinatal Asphyxia

Neonatology ◽  
2020 ◽  
Vol 117 (4) ◽  
pp. 488-494
Author(s):  
Corline E.J. Parmentier ◽  
Linda S. de Vries ◽  
Mona C. Toet ◽  
Ingrid C. van Haastert ◽  
Corine Koopman ◽  
...  
Keyword(s):  
Therapeutic Hypothermia ◽  
Clinical Experience ◽  
Perinatal Asphyxia ◽  
Neurodevelopmental Outcome ◽  
Adverse Outcomes ◽  
Neonatal Encephalopathy ◽  
Neurodevelopmental Outcomes ◽  
Period 2 ◽  
Second Period

<b><i>Introduction:</i></b> Adverse outcomes have been reported in infants with mild neonatal encephalopathy (NE). Increasing clinical experience with the application of therapeutic hypothermia (TH) may have resulted in the treatment of newborns with milder NE during recent years. <b><i>Objective:</i></b> To determine whether infants treated with TH in the initial years following implementation had a higher degree of NE than infants treated during subsequent years. <b><i>Methods:</i></b> Infants with NE treated with TH from February 2008 until July 2017 were included. Thompson and Sarnat scores, amplitude-integrated electroencephalography (aEEG) background patterns before the start of TH, and neurodevelopmental outcome at 2 years were compared between infants treated from February 2008 until October 2012 (period 1) and infants treated from November 2012 until July 2017 (period 2). <b><i>Results:</i></b> 211 newborns with NE were treated with TH (period 1: <i>n</i> = 109, period 2: <i>n</i> = 102). Sarnat scores in period 1 and 2 were mild in 7.3 vs. 28.4%, moderate in 66.1 vs. 44.1%, and severe in 26.6 vs. 22.5%, respectively (<i>p</i> = 0.008). Thompson scores were lower in period 2 (median = 9, IQR 7–12) than in period 1 (median = 10, IQR 8.5–13.5, <i>p</i> = 0.018). The aEEGs and neurodevelopmental outcomes were comparable between the periods. <b><i>Conclusions:</i></b> Based on Thompson and Sarnat scores, but not aEEG background patterns, infants treated during the second period had milder NE than infants treated during the first years following implementation of TH. There was no difference in 2 years neurodevelopmental outcome. Further research is necessary to evaluate the value of TH for infants with clinically mild NE.

Therapeutic hypothermia for mild neonatal encephalopathy: a systematic review and meta-analysis

2018 ◽  
Vol 105 (2) ◽  
pp. 225-228 ◽  
Author(s):  
Ujwal Kariholu ◽  
Paolo Montaldo ◽  
Theodora Markati ◽  
Peter J Lally ◽  
Russell Pryce ◽  
...  
Keyword(s):  
Usual Care ◽  
Therapeutic Hypothermia ◽  
Data Extraction ◽  
Meta Analysis ◽  
Adverse Outcomes ◽  
Whole Body ◽  
Current Evidence ◽  
Neonatal Encephalopathy ◽  
Medical Subject Headings ◽  
Manual Search

ObjectivesTo examine if therapeutic hypothermia reduces the composite outcome of death, moderate or severe disability at 18 months or more after mild neonatal encephalopathy (NE).Data sourceMEDLINE, Cochrane database, Scopus and ISI Web of Knowledge databases, using ‘hypoxic ischaemic encephalopathy’, ‘newborn’ and ‘hypothermia’, and ‘clinical trials’ as medical subject headings and terms. Manual search of the reference lists of all eligible articles and major review articles and additional data from the corresponding authors of selected articles.Study selectionRandomised and quasirandomised controlled trials comparing therapeutic hypothermia with usual care.Data extractionSafety and efficacy data extracted independently by two reviewers and analysed.ResultsWe included the data on 117 babies with mild NE inadvertently recruited to five cooling trials (two whole-body cooling and three selective head cooling) of moderate and severe NE, in the meta-analysis. Adverse outcomes occurred in 11/56 (19.6%) of the cooled babies and 12/61 (19.7%) of the usual care babies (risk ratio 1.11 (95% CIs 0.55 to 2.25)).ConclusionsCurrent evidence is insufficient to recommend routine therapeutic hypothermia for babies with mild encephalopathy and significant benefits or harm cannot be excluded.

scholarly journals Predicting developmental outcomes in preterm infants

Neurology ◽  
2019 ◽  
Vol 93 (13) ◽  
pp. e1231-e1240 ◽  
Author(s):  
Dalit Cayam-Rand ◽  
Ting Guo ◽  
Ruth E. Grunau ◽  
Isabel Benavente-Fernández ◽  
Anne Synnes ◽  
...  
Keyword(s):  
Characteristic Curve ◽  
Brain Mri ◽  
Adverse Outcomes ◽  
Preschool Age ◽  
Cognitive Outcomes ◽  
White Matter Injury ◽  
Preterm Neonates ◽  
Posterior Commissure ◽  
Neurodevelopmental Outcomes ◽  
Motor Outcomes

ObjectiveTo develop a simple imaging rule to predict neurodevelopmental outcomes at 4.5 years in a cohort of preterm neonates with white matter injury (WMI) based on lesion location and examine whether clinical variables enhance prediction.MethodsSixty-eight preterm neonates born 24–32 weeks' gestation (median 27.7 weeks) were diagnosed with WMI on early brain MRI scans (median 32.3 weeks). 3D T1-weighted images of 60 neonates with 4.5-year outcomes were reformatted and aligned to the posterior commissure–eye plane and WMI was classified by location: anterior or posterior-only to the midventricle line on the reformatted axial plane. Adverse outcomes at 4.5 years were defined as Wechsler Preschool and Primary Scale of Intelligence full-scale IQ <85, cerebral palsy, or Movement Assessment Battery for Children, second edition percentile <5. The prediction of adverse outcome by WMI location, intraventricular hemorrhage (IVH), bronchopulmonary dysplasia (BPD), and retinopathy of prematurity (ROP) was assessed using multivariable logistic regression.ResultsSix children had adverse cognitive outcomes and 17 had adverse motor outcomes. WMI location predicted cognitive outcomes in 90% (area under receiver operating characteristic curve [AUC] 0.80) and motor outcomes in 85% (AUC 0.75). Adding IVH, BPD, and ROP to the model enhances the predictive strength for cognitive and motor outcomes (AUC 0.83 and 0.88, respectively). Rule performance was confirmed in an independent cohort of children with WMI.ConclusionsWMI on early MRI can be classified by location to predict preschool age outcomes in children born preterm. The predictive value of this WMI classification is enhanced by considering clinical factors apparent by term-equivalent age.

scholarly journals Outcomes of Infants with Mild Hypoxic Ischemic Encephalopathy Who Did Not Receive Therapeutic Hypothermia

2019 ◽  
Vol 4 (3) ◽  
pp. 1-9 ◽  
Author(s):  
Jonathan Reiss ◽  
Mridu Sinha ◽  
Jeffrey Gold ◽  
Julie Bykowski ◽  
Shelley M. Lawrence
Keyword(s):  
Therapeutic Hypothermia ◽  
Severe Disease ◽  
Significant Risk ◽  
Brain Magnetic Resonance Imaging ◽  
Adverse Outcomes ◽  
Hypoxic Ischemic Encephalopathy ◽  
Neurodevelopmental Outcomes ◽  
Specific Patient ◽  
Increased Risk ◽  
Ischemic Encephalopathy

Introduction: Accurately diagnosing and treating infants with mild forms of hypoxic ischemic encephalopathy (HIE) is important, as the majority of neonates with signs and symptoms of HIE after birth do not meet clinical criteria for moderate or severe disease. Emerging evidence, however, suggests that infants with mild HIE (mHIE) have an increased risk for neurodevelopmental impairment (NDI). Methods: This retrospective descriptive study examined all inborn infants ≥35 week’s gestational age at a single, level III neonatal intensive care unit (NICU) in California between January 1, 2012, and December 31, 2015. International Classification of Diseases codes were used as a proxy to identify neonates with mHIE but who did not receive therapeutic hypothermia (TH). Short- and long-term neurodevelopmental outcomes were documented, including abnormal (1) brain magnetic resonance imaging within 10 days of birth suggestive of HIE, (2) electroencephalogram with electrographic seizures, (3) neurologic discharge examination, or (4) NDI following NICU discharge. Results: Over the 4-year study period, 25 infants met inclusion criteria. Eight of 25 (32%) infants demonstrated neurologic impairment, defined by an abnormality in at least one of the four categories. The remaining 17 infants were without documented evidence for adverse outcomes. Conclusion: Our results indicate that children with mHIE are at significant risk for neurologic injury and may benefit from more aggressive interventions. Further prospective studies should be completed to determine the efficacy of TH in this specific patient population.

Diffusion tensor imaging in neonatal encephalopathy: a systematic review

2019 ◽  
Vol 105 (5) ◽  
pp. 480-488 ◽  
Author(s):  
Megan Dibble ◽  
Mary Isabel O'Dea ◽  
Tim Hurley ◽  
Angela Byrne ◽  
Gabrielle Colleran ◽  
...  
Keyword(s):  
Diffusion Tensor Imaging ◽  
White Matter ◽  
Diffusion Tensor ◽  
Neurodevelopmental Outcome ◽  
Internal Capsule ◽  
Adverse Outcomes ◽  
Restricted Diffusion ◽  
Neonatal Encephalopathy ◽  
White Matter Tracts ◽  
Posterior Limb

Background and objectiveDiffusion tensor imaging (DTI) during the first few days of life can be used to assess brain injury in neonates with neonatal encephalopathy (NE) for outcome prediction. The goal of this review was to identify specific white matter tracts of interest that can be quantified by DTI as being altered in neonates with this condition, and to investigate its potential prognostic ability.MethodsSearches of Medline and the Cochrane Database of Systematic Reviews were conducted to identify studies with diffusion data collected in term-born neonates with NE.Results19 studies were included which described restricted diffusion in encephalopathic neonates as compared with healthy controls, with the posterior limb of the internal capsule and the genu and splenium of the corpus callosum identified as particular regions of interest. Restricted diffusion was related to adverse outcomes in the studies that conducted a follow-up of these infants.ConclusionsObtaining diffusion measures in these key white matter tracts early in life before pseudonormalisation can occur can not only identify the extent of the damage but also can be used to examine the effectiveness of treatment and to predict neurodevelopmental outcome.

Neurodevelopmental Outcomes in Preterm Infants with White Matter Injury Using a New MRI Classification

Neonatology ◽  
2019 ◽  
Vol 116 (3) ◽  
pp. 227-235 ◽  
Author(s):  
Miriam Martinez-Biarge ◽  
Floris Groenendaal ◽  
Karina J. Kersbergen ◽  
Manon J.N.L. Benders ◽  
Francesca Foti ◽  
...  
Keyword(s):  
White Matter ◽  
Preterm Infants ◽  
White Matter Injury ◽  
Neurodevelopmental Outcomes

Occult Massive Visceral Fat Necrosis Following Therapeutic Hypothermia for Neonatal Encephalopathy

2017 ◽  
Vol 21 (5) ◽  
pp. 502-506
Author(s):  
Salwa Khedr ◽  
Anna Piskorski ◽  
Adrienne R Bingham ◽  
Justin Goldstein ◽  
Abbot R Laptook ◽  
...  
Keyword(s):  
Therapeutic Hypothermia ◽  
Visceral Fat ◽  
Subcutaneous Fat ◽  
Neurodevelopmental Outcome ◽  
Pulmonary Artery Hypertension ◽  
Whole Body ◽  
Common Side Effect ◽  
Close Monitoring ◽  
Fat Necrosis ◽  
Subcutaneous Fat Necrosis

Therapeutic hypothermia (head or whole-body cooling) improves survival and neurodevelopmental outcome in term newborns with moderate-to-severe encephalopathy. Hypothermia treatment is well tolerated; the most common side effect is thrombocytopenia. In about 1% of infants, focal subcutaneous fat necrosis has been reported. We describe a case of clinically unsuspected massive visceral fat necrosis in a term infant with Apgar score 0 at 1 min (“resuscitated apparently stillborn” infant) who was treated with therapeutic hypothermia for 72 h and expired on the 25th day of life following a neonatal course complicated by severe encephalopathy, pulmonary artery hypertension, persistent thrombocytopenia, hypoglycemia, and severe basal ganglia-thalamic abnormalities on magnetic resonance imaging. Postmortem examination revealed extensive visceral (brown) fat necrosis, involving thoracic, abdominal, and retroperitoneal adipose tissue, with distinctive sparing of the subcutaneous (white) fat. The fulminant—yet clinically occult—visceral fat necrosis seen in this case suggests that (lesser degrees of) fat necrosis may go unrecognized in hypoxic-ischemic newborns, especially in those treated with hypothermia, and underscores the importance of close monitoring of encephalopathic newborns both in the short and long terms for complications of fat necrosis (hypercalcemia and nephrocalcinosis).

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