19 results on '"Edwards AD"'
Search Results
2. Common genetic variants and risk of brain injury after preterm birth.
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Boardman JP, Walley A, Ball G, Takousis P, Krishnan ML, Hughes-Carre L, Aljabar P, Serag A, King C, Merchant N, Srinivasan L, Froguel P, Hajnal J, Rueckert D, Counsell S, and Edwards AD
- Subjects
- Alleles, Armadillo Domain Proteins genetics, Brain pathology, Catechol O-Methyltransferase genetics, Cell Adhesion Molecules genetics, Chromosomes, Human, Pair 11 genetics, Chromosomes, Human, Pair 22 genetics, Cohort Studies, Diffusion Magnetic Resonance Imaging, Endophenotypes, Fatty Acid Desaturases genetics, Gene Library, Genetic Carrier Screening, Genotype, Humans, Image Interpretation, Computer-Assisted, Infant, Newborn, Intelligence genetics, Magnetic Resonance Imaging, Phosphoproteins genetics, Polymorphism, Single Nucleotide genetics, Schizophrenia genetics, Brain Damage, Chronic diagnosis, Brain Damage, Chronic genetics, Genetic Association Studies, Genetic Predisposition to Disease genetics, Genetic Variation genetics, Infant, Premature, Diseases diagnosis, Infant, Premature, Diseases genetics
- Abstract
Background: The role of heritable factors in determining the common neurologic deficits seen after preterm birth is unknown, but the characteristic phenotype of neurocognitive, neuroanatomical, and growth abnormalities allows principled selection of candidate genes to test the hypothesis that common genetic variation modulates the risk for brain injury., Methods: We collected an MRI-linked genomic DNA library from 83 preterm infants and genotyped tag single nucleotide polymorphisms in 13 relevant candidate genes. We used tract-based spatial statistics and deformation-based morphometry to examine the risks conferred by carriage of particular alleles at tag single nucleotide polymorphisms in a restricted number of genes and related these to the preterm cerebral endophenotype., Results: Carriage of the minor allele at rs2518824 in the armadillo repeat gene deleted in velocardiofacial syndrome (ARVCF) gene, which has been linked to neuronal migration and schizophrenia, and rs174576 in the fatty acid desaturase 2 gene, which encodes a rate-limiting enzyme for endogenous long chain polyunsaturated fatty acid synthesis and has been linked to intelligence, was associated with white matter abnormality measured in vivo using diffusion tensor imaging (P = .0009 and P = .0019, respectively)., Conclusions: These results suggest that genetic variants modulate white matter injury after preterm birth, and known susceptibilities to neurologic status in later life may be exposed by the stress of premature exposure to the extrauterine environment., (Copyright © 2014 by the American Academy of Pediatrics.)
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- 2014
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3. Subcutaneous fat necrosis after moderate therapeutic hypothermia in neonates.
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Strohm B, Hobson A, Brocklehurst P, Edwards AD, and Azzopardi D
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- Humans, Hypoxia-Ischemia, Brain diagnosis, Hypoxia-Ischemia, Brain therapy, Infant, Newborn, Treatment Outcome, Fat Necrosis diagnosis, Fat Necrosis etiology, Hypothermia, Induced adverse effects, Subcutaneous Fat pathology
- Abstract
Therapeutic moderate hypothermia in newborns with hypoxic-ischemic encephalopathy is rapidly becoming standard clinical practice. We report here 12 cases of subcutaneous fat necrosis among 1239 cases registered with a national registry of newborns treated with moderate whole-body hypothermia. All the infants suffered from perinatal asphyxia and hypoxic-ischemic encephalopathy. Moderate-to-severe hypercalcemia was identified in 8 of 10 infants with blood calcium measurements. In all cases the skin lesions appeared after completion of the cooling treatment. Our data suggest that prolonged moderate hypothermia is an actual risk factor for subcutaneous fat necrosis. Because the lesions often develop several days after birth, physicians need to be aware of this condition as a possible complication in infants treated with moderate hypothermia after asphyxia. Blood calcium levels need to be monitored in affected infants.
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- 2011
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4. The association of lung disease with cerebral white matter abnormalities in preterm infants.
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Anjari M, Counsell SJ, Srinivasan L, Allsop JM, Hajnal JV, Rutherford MA, and Edwards AD
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- Anisotropy, Corpus Callosum pathology, Female, Gestational Age, Humans, Infant, Newborn, Male, Multivariate Analysis, Respiration, Artificial, Cerebrum pathology, Developmental Disabilities pathology, Diffusion Magnetic Resonance Imaging methods, Image Processing, Computer-Assisted methods, Infant, Premature, Lung Diseases epidemiology, Lung Diseases pathology, Neural Pathways pathology
- Abstract
Objective: Preterm infants have a high incidence of neurodevelopmental impairment associated with diffuse cerebral white matter abnormalities and also a high incidence of serious respiratory disease. However, it is unclear if lung disease and brain injury are related, and previous research has been impeded by confounding effects, including prematurity and infection. Using a new approach that permits multivariate statistical analysis, we tested the hypothesis that lung disease is associated with specific white matter abnormalities, detected as reduced fractional anisotropy (FA) in diffusion tensor imaging data., Methods: Fifty-three preterm infants with no evidence of focal abnormality on conventional MRI were studied at term-equivalent age by using tract-based spatial statistics, an automated observer-independent method for voxelwise analysis of major white matter pathways., Results: In several white matter tracts, FA decreased with a linear relation to the gestational age at birth. Independent of the confounding effects of prematurity and age at scan, respiratory disease was associated with specific white matter abnormalities in preterm infants; those infants receiving mechanical ventilation for >2 days in the perinatal period (n = 10) showed reduced FA in the genu of the corpus callosum, whereas subjects with chronic lung disease (n = 15) displayed a reduction in FA in the left inferior longitudinal fasciculus., Conclusion: Independent of the degree of prematurity, respiratory disease is associated with cerebral white matter abnormalities.
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- 2009
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5. Does head cooling with mild systemic hypothermia affect requirement for blood pressure support?
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Battin MR, Thoresen M, Robinson E, Polin RA, Edwards AD, and Gunn AJ
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- Electroencephalography, Female, Fluid Therapy, Homeostasis, Humans, Hypoxia-Ischemia, Brain physiopathology, Infant, Newborn, Male, Monitoring, Physiologic, Rewarming, Blood Pressure physiology, Head, Heart Rate physiology, Hypothermia, Induced methods, Hypoxia-Ischemia, Brain therapy
- Abstract
Objective: Our goal was to evaluate whether head cooling with mild systemic hypothermia for neonatal encephalopathy is associated with greater requirement for volume or inotrope support., Patients and Methods: We studied term infants (>/=36 weeks) with moderate-to-severe neonatal encephalopathy plus abnormal amplitude integrated electroencephalography, randomly assigned to head cooling for 72 hours starting within 6 hours of birth, with the rectal temperature maintained at 34.5 degrees C +/- 0.5 degrees C (n = 112), or conventional care (n = 118)., Design: This was a multicenter randomized, controlled study (the CoolCap trial). The primary outcome was the time relationship between mean arterial blood pressure and subsequent administration of inotropes or volume administration., Results: Pooled data from 0 to 76 hours after randomization revealed no difference in mean arterial blood pressure between groups and significantly lower mean heart rate during cooling. The use of inotropes or volume was related to preceding mean arterial blood pressure and not to treatment group in the first 24 hours. In contrast, from 24 to 76 hours, there was no effect of mean arterial blood pressure, but there was an overall reduction in pressure support over time and significantly more frequent pressure support in the cooled group than in controls., Conclusions: Mild systemic hypothermia did not affect arterial blood pressure or initial treatment with inotropes or volume in infants with moderate-to-severe encephalopathy but was associated with an apparent change in physician behavior, with slower withdrawal of therapy in cooled infants.
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- 2009
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6. Three-tesla cardiac magnetic resonance imaging for preterm infants.
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Foran AM, Fitzpatrick JA, Allsop J, Schmitz S, Franklin J, Pamboucas C, O'Regan D, Hajnal JV, and Edwards AD
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- Cardiac Output, Cardiac Volume, Humans, Image Processing, Computer-Assisted, Infant, Premature, Stroke Volume, Infant, Newborn physiology, Magnetic Resonance Imaging, Cine methods, Ventricular Function, Left
- Abstract
Objectives: We aimed to establish the feasibility of acquiring 3.0-T cardiac MRIs without sedation, anesthesia, or breath-holding for preterm infants and to obtain preliminary quantitative data on left ventricular function in this population., Methods: Twelve preterm infants underwent 3.0-T cardiac MRI without sedation or breath-holding. The median gestational age was 29 weeks (range: 26-33 weeks), the median birth weight was 1240 g (range: 808-2200 g), and the median postconceptional age at the time of cardiac MRI was 33 weeks (range: 31-40 weeks). Anatomic images were acquired with T2-weighted spin-echo sequences, and ventricular function was assessed with balanced steady-state free precession cine sequences. We assessed left ventricular function by using the area-length ejection fraction method on horizontal long-axis images and the volumetric Sergeant's discs method of analysis on short-axis images., Results: Imaging was successful for 10 of 12 infants. For those 10, the area-length ejection fraction method in the horizontal long-axis plane estimated median stroke volume at 2.9 mL, cardiac output at 0.4 L/minute, end-diastolic volume at 3.8 mL, end-systolic volume at 0.3 mL, and ejection fraction at 74.6%. Short-axis volumetric estimations were made for 4 infants. With this approach, the median stroke volume was 2.4 mL, cardiac output 0.35 L/minute, end-diastolic volume 4.3 mL, end-systolic volume 2.1 mL, and ejection fraction 56%., Conclusions: Three-tesla cardiac MRI is feasible for preterm infants without sedation, anesthesia, or breath-holding and has the potential to provide a wide range of precise quantitative data that may be of great value for the investigation of cardiac function in preterm infants.
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- 2007
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7. Determinants of outcomes after head cooling for neonatal encephalopathy.
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Wyatt JS, Gluckman PD, Liu PY, Azzopardi D, Ballard R, Edwards AD, Ferriero DM, Polin RA, Robertson CM, Thoresen M, Whitelaw A, and Gunn AJ
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- Electroencephalography, Female, Humans, Hypoxia-Ischemia, Brain diagnosis, Hypoxia-Ischemia, Brain physiopathology, Infant, Newborn, Male, Head physiology, Hypothermia, Induced methods, Hypoxia-Ischemia, Brain therapy
- Abstract
Objective: The goal of this study was to evaluate the role of factors that may determine the efficacy of treatment with delayed head cooling and mild systemic hypothermia for neonatal encephalopathy., Methods: A total of 218 term infants with moderate to severe neonatal encephalopathy plus abnormal amplitude-integrated electroencephalographic recordings, assigned randomly to head cooling for 72 hours, starting within 6 hours after birth (with the rectal temperature maintained at 34.5 +/- 0.5 degrees C), or conventional care, were studied. Death or severe disability at 18 months of age was assessed in a multicenter, randomized, controlled study (the CoolCap trial)., Results: Treatment, lower encephalopathy grade, lower birth weight, greater amplitude-integrated electroencephalographic amplitude, absence of seizures, and higher Apgar score, but not gender or gestational age, were associated significantly with better outcomes. In a multivariate analysis, each of the individually predictive factors except for Apgar score remained predictive. There was a significant interaction between treatment and birth weight, categorized as > or =25th or <25th percentile for term, such that larger infants showed a lower frequency of favorable outcomes in the control group but greater improvement with cooling. For larger infants, the number needed to treat was 3.8. Pyrexia (> or =38 degrees C) in control infants was associated with adverse outcomes. Although there was a small correlation with birth weight, the adverse effect of greater birth weight in control infants remained significant after adjustment for pyrexia and severity of encephalopathy., Conclusions: Outcomes after hypothermic treatment were strongly influenced by the severity of neonatal encephalopathy. The protective effect of hypothermia was greater in larger infants.
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- 2007
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8. Quantification of deep gray matter in preterm infants at term-equivalent age using manual volumetry of 3-tesla magnetic resonance images.
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Srinivasan L, Dutta R, Counsell SJ, Allsop JM, Boardman JP, Rutherford MA, and Edwards AD
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- Basal Ganglia embryology, Case-Control Studies, Cohort Studies, Female, Follow-Up Studies, Gestational Age, Humans, Infant, Infant, Newborn, Intensive Care Units, Neonatal, Male, Observer Variation, Reference Values, Reproducibility of Results, Sensitivity and Specificity, Term Birth, Thalamus embryology, Basal Ganglia pathology, Image Processing, Computer-Assisted, Infant, Premature, Magnetic Resonance Imaging methods, Thalamus pathology
- Abstract
Objective: Nonhypothesis-based MRI-analysis techniques including deformation-based morphometry and automated tissue segmentation have suggested that preterm infants at term-equivalent age have reduced tissue volume in the basal ganglia and thalami, which is most apparent among infants with supratentorial lesions. The aim of our study was to test this hypothesis by direct measurement of thalamic and lentiform nuclei volumes in preterm infants at term-equivalent age and term-born controls using manual volumetry., Design/methods: Forty preterm infants at term-equivalent age (median gestational age: 29.5 weeks; median birth weight: 1.3 kg) and 8 term-born controls were examined using a 3-T Philips (Best, Netherlands) system. T1-weighted volume images and T2-weighted fast-spin echo pseudovolumes were acquired. There was no significant difference in postmenstrual age at image acquisition between the 2 groups. ImageJ 1.34 (National Institutes of Health, Bethesda, MD) was used for manual segmentations., Results: The median thalamic and lentiform nuclei volumes for preterm infants at term-equivalent age were 13.6 and 3.07 cm3, respectively, significantly smaller than term-control volumes of 16.3 and 5.6 cm3, respectively. Ten preterm infants at term-equivalent age had supratentorial lesions (intraventricular hemorrhage, periventricular leukomalacia, or hemorrhagic parenchymal infarction), and the median thalamic and lentiform volumes for this group were 10.4 and 1.7 cm3, respectively. When this group was excluded, the remaining infants who had mild or moderate diffuse excessive high signal intensity in the white matter on T2-weighted images had a smaller, yet significant, volume reduction compared with controls. Tissue volumes were not related to weight and gestational age at birth., Conclusions: Manual volumetry confirms that preterm infants at term-equivalent age have reduced thalamic and lentiform volumes compared with controls. This was most marked among infants with supratentorial lesions but was also seen among those with nonfocal white matter abnormalities.
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- 2007
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9. Natural history of brain lesions in extremely preterm infants studied with serial magnetic resonance imaging from birth and neurodevelopmental assessment.
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Dyet LE, Kennea N, Counsell SJ, Maalouf EF, Ajayi-Obe M, Duggan PJ, Harrison M, Allsop JM, Hajnal J, Herlihy AH, Edwards B, Laroche S, Cowan FM, Rutherford MA, and Edwards AD
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- Basal Ganglia pathology, Brain Damage, Chronic etiology, Cerebral Hemorrhage etiology, Cerebral Hemorrhage pathology, Cerebral Infarction etiology, Cerebral Infarction pathology, Cerebral Palsy epidemiology, Cerebral Palsy etiology, Cerebral Ventricles pathology, Cohort Studies, Developmental Disabilities etiology, Dilatation, Pathologic etiology, Dilatation, Pathologic pathology, Female, Fetal Growth Retardation pathology, Follow-Up Studies, Gestational Age, Humans, Infant, Infant, Newborn, Infant, Premature, Infant, Small for Gestational Age, Intensive Care Units, Neonatal, Leukomalacia, Periventricular etiology, Leukomalacia, Periventricular pathology, London epidemiology, Male, Neuropsychological Tests, Severity of Illness Index, Brain pathology, Brain Damage, Chronic pathology, Developmental Disabilities pathology, Infant, Premature, Diseases pathology, Magnetic Resonance Imaging
- Abstract
Objectives: The aim was to survey the range of cerebral injury and abnormalities of cerebral development in infants born between 23 and 30 weeks' gestation using serial MRI scans of the brain from birth, and to correlate those findings with neurodevelopmental outcome after 18 months corrected age., Methods: Between January 1997 and November 2000, consecutive infants born at < 30 weeks' gestational age underwent serial MRI brain scans from birth until term-equivalent age. Infants were monitored after 18 months of age, corrected for prematurity, with the Griffiths Mental Development Scales and neurologic assessment., Results: A total of 327 MRI scans were obtained from 119 surviving infants born at 23 to 30 weeks of gestation. Four infants had major destructive brain lesions, and tissue loss was seen at term for the 2 survivors. Fifty-one infants had early hemorrhage; 50% of infants with term scans after intraventricular hemorrhage had ventricular dilation. Twenty-six infants had punctate white matter lesions on early scans; these persisted for 33% of infants assessed at term. Early scans showed cerebellar hemorrhagic lesions for 8 infants and basal ganglia abnormalities for 17. At term, 53% of infants without previous hemorrhage had ventricular dilation and 80% of infants had diffuse excessive high signal intensity within the white matter on T2-weighted scans. Complete follow-up data were available for 66% of infants. Adverse outcomes were associated with major destructive lesions, diffuse excessive high signal intensity within the white matter, cerebellar hemorrhage, and ventricular dilation after intraventricular hemorrhage but not with punctate white matter lesions, hemorrhage, or ventricular dilation without intraventricular hemorrhage., Conclusions: Diffuse white matter abnormalities and post-hemorrhagic ventricular dilation are common at term and seem to correlate with reduced developmental quotients. Early lesions, except for cerebellar hemorrhage and major destructive lesions, do not show clear relationships with outcomes.
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- 2006
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10. Axial and radial diffusivity in preterm infants who have diffuse white matter changes on magnetic resonance imaging at term-equivalent age.
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Counsell SJ, Shen Y, Boardman JP, Larkman DJ, Kapellou O, Ward P, Allsop JM, Cowan FM, Hajnal JV, Edwards AD, and Rutherford MA
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- Female, Gestational Age, Humans, Image Processing, Computer-Assisted, Infant, Newborn, Magnetic Resonance Imaging, Male, Term Birth, Brain anatomy & histology, Diffusion Magnetic Resonance Imaging, Infant, Premature
- Abstract
Objective: Diffuse excessive high signal intensity (DEHSI) is observed in the majority of preterm infants at term-equivalent age on conventional MRI, and diffusion-weighted imaging has shown that apparent diffusion coefficient values are elevated in the white matter (WM) in DEHSI. Our aim was to obtain diffusion tensor imaging on preterm infants at term-equivalent age and term control infants to test the hypothesis that radial diffusivity was significantly different in the WM in preterm infants with DEHSI compared with both preterm infants with normal-appearing WM on conventional MRI and term control infants., Methods: Diffusion tensor imaging was obtained on 38 preterm infants at term-equivalent age and 8 term control infants. Values for axial (lambda1) and radial [(lambda2 + lambda3)/2] diffusivity were calculated in regions of interest positioned in the central WM at the level of the centrum semiovale, frontal WM, posterior periventricular WM, occipital WM, anterior and posterior portions of the posterior limb of the internal capsule, and the genu and splenium of the corpus callosum., Results: Radial diffusivity was elevated significantly in the posterior portion of the posterior limb of the internal capsule and the splenium of the corpus callosum, and both axial and radial diffusivity were elevated significantly in the WM at the level of the centrum semiovale, the frontal WM, the periventricular WM, and the occipital WM in preterm infants with DEHSI compared with preterm infants with normal-appearing WM and term control infants. There was no significant difference between term control infants and preterm infants with normal-appearing WM in any region studied., Conclusions: These findings suggest that DEHSI represents an oligodendrocyte and/or axonal abnormality that is widespread throughout the cerebral WM.
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- 2006
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11. Mild hypothermia and the distribution of cerebral lesions in neonates with hypoxic-ischemic encephalopathy.
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Rutherford MA, Azzopardi D, Whitelaw A, Cowan F, Renowden S, Edwards AD, and Thoresen M
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- Brain pathology, Cerebral Hemorrhage complications, Cerebral Hemorrhage diagnosis, Electroencephalography, Humans, Hypoxia-Ischemia, Brain complications, Hypoxia-Ischemia, Brain pathology, Hypoxia-Ischemia, Brain physiopathology, Image Processing, Computer-Assisted, Infant, Newborn, Magnetic Resonance Imaging, Hypothermia, Induced, Hypoxia-Ischemia, Brain therapy
- Abstract
Hypothermia induced by whole-body cooling (WBC) and selective head cooling (SHC) both reduce brain injury after hypoxia-ischemia in newborn animals, but it is not known how these treatments affect the incidence or pattern of brain injury in human newborns. To assess this, 14 term infants with hypoxic-ischemic encephalopathy (HIE) treated with SHC, 20 infants with HIE treated with WBC, and 52 noncooled infants with HIE of similar severity were studied with magnetic resonance imaging in the neonatal period. Infants fulfilling strict criteria for HIE were recruited into the study after assessment of an amplitude-integrated electroencephalography (aEEG). Cooling was commenced within 6 hours of birth and continued for 48 to 72 hours. Hypothermia was not associated with unexpected or unusual lesions, and the prevalence of intracranial hemorrhage was similar in all 3 groups. Both modes of hypothermia were associated with a decrease in basal ganglia and thalamic lesions, which are predictive of abnormal outcome. This decrease was significant in infants with a moderate aEEG finding but not in those with a severe aEEG finding. A decrease in the incidence of severe cortical lesions was seen in the infants treated with SHC.
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- 2005
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12. Diffusion-weighted imaging of the brain in preterm infants with focal and diffuse white matter abnormality.
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Counsell SJ, Allsop JM, Harrison MC, Larkman DJ, Kennea NL, Kapellou O, Cowan FM, Hajnal JV, Edwards AD, and Rutherford MA
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- Body Water metabolism, Diffusion, Humans, Infant, Newborn, Leukomalacia, Periventricular metabolism, Brain pathology, Infant, Premature, Leukomalacia, Periventricular pathology, Magnetic Resonance Imaging methods
- Abstract
Objective: The most common finding on magnetic resonance imaging (MRI) of the brain in preterm infants at term-equivalent age is diffuse excessive high signal intensity (DEHSI) in the white matter. It is unclear whether DEHSI represents a biological abnormality. This study used diffusion-weighted imaging (DWI) to compare apparent diffusion coefficient (ADC) values in DEHSI with infants with normal imaging and those with overt brain damage to determine whether DEHSI shows the diffusion characteristics of normal or abnormal tissue., Methods: MRI, using conventional and diffusion-weighted imaging (DWI), was performed in 50 preterm infants at term-equivalent age using a 1.5 Tesla MR scanner. The infants were divided into 3 groups on the basis of their MRI results: 1) normal white matter, 2) DEHSI, or 3) overt white matter pathology. ADC values were measured in the frontal, central, and posterior white matter at the level of the centrum semiovale. ADC values in the 3 groups of preterm infants were compared using a 1-way analysis of variance with a Bonferroni test for multiple comparisons., Results: ADC values were significantly higher in infants with DEHSI and infants with overt white matter pathology than in infants with normal white matter. There was no significant difference between ADC values in infants with DEHSI and those with overt white matter pathology., Conclusions: This study provides objective evidence that DEHSI represents diffuse white matter abnormality.
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- 2003
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13. Prothrombotic disorders and abnormal neurodevelopmental outcome in infants with neonatal cerebral infarction.
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Mercuri E, Cowan F, Gupte G, Manning R, Laffan M, Rutherford M, Edwards AD, Dubowitz L, and Roberts I
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- Activated Protein C Resistance epidemiology, Cerebral Infarction blood, Cerebral Infarction epidemiology, Developmental Disabilities blood, Developmental Disabilities epidemiology, Factor V analysis, Factor V genetics, Factor VIII analysis, Factor VIII genetics, Humans, Infant, Newborn, Magnetic Resonance Imaging statistics & numerical data, Nervous System Diseases blood, Nervous System Diseases epidemiology, Risk Factors, Thrombophilia blood, Thrombophilia genetics, Activated Protein C Resistance blood, Cerebral Infarction diagnosis, Developmental Disabilities diagnosis, Nervous System Diseases diagnosis, Thrombophilia diagnosis
- Abstract
Background and Purpose: The aim of this study was to evaluate the occurrence of prothrombotic disorders in a well-characterized cohort of infants with neonatal stroke and to document any association of prothrombotic disorders with the type of infarct seen on magnetic resonance imaging (MRI) and clinical outcome., Methods: Twenty-four infants with perinatal cerebral infarction confirmed by neonatal MRI were enrolled in the study. All the infants and, when possible, both parents were tested to identify inherited and acquired prothrombotic disorders., Results: None of the infants had a significant bleeding diathesis, but 10 (42%) had at least 1 prothrombotic risk factor. Five children showed heterozygosity for factor V Leiden, and 6 had high factor VIIIc concentrations. There was a striking association between the occurrence of these abnormalities and both the presence of cerebral hemorrhage on MRI and poor neurologic outcome. Eight of the 11 patients (73%) with hemiplegia or global developmental delay had factor V Leiden and/or raised factor VIIIc, whereas only 1 of the 13 patients (8%) with normal outcome had any prothrombotic risk factors. In particular, all 5 infants with factor V Leiden had hemiplegia, compared with only 4 of the 19 infants without factor V Leiden (21%)., Conclusions: These data suggest that the presence of prothrombotic risk factors and, in particular, of the factor V Leiden mutation, is significantly associated with poor outcome after perinatal cerebral infarction.
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- 2001
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14. Comparison of findings on cranial ultrasound and magnetic resonance imaging in preterm infants.
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Maalouf EF, Duggan PJ, Counsell SJ, Rutherford MA, Cowan F, Azzopardi D, and Edwards AD
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- Brain pathology, Cerebral Hemorrhage diagnostic imaging, Cerebral Hemorrhage pathology, Humans, Infant, Newborn, Brain anatomy & histology, Echoencephalography statistics & numerical data, Infant, Premature physiology, Magnetic Resonance Imaging statistics & numerical data
- Abstract
Objective: To compare findings on hard copies of cranial ultrasound (US) and magnetic resonance imaging (MRI) obtained between birth and term in a group of preterm infants., Participants and Methods: Infants born at or below a gestational age of 30 weeks who underwent cranial US scan and MRI on the same day were eligible for this study. Infants underwent, whenever possible, 3 scans between birth and term. We calculated the predictive probability (PP) of US findings as a predictor of findings on MRI., Results: Sixty-two paired MRI and US studies were performed between birth and term in 32 infants born at a median gestational age of 27 (range: 23-30) weeks and a median birth weight of 918 (530-1710) grams. US predicted some MRI findings accurately: germinal layer hemorrhage (GLH) on US had a PP of 0.8 with a 95% confidence interval of (0.70-0.90) for the presence of GLH on MRI, intraventricular hemorrhage (IVH) on US had a PP of 0.85 (0.76-0.94) for the presence of IVH on MRI, and severe white matter (WM) echogenicity on US had a PP of 0.96 (0.92-1.0) for the presence of WM hemorrhagic parenchymal infarction on MRI. Other MRI changes were less well-predicted: mild or no WM echogenicity on US had a PP of 0.54 (0.41-0.66) for the presence of normal WM signal intensity on MRI, and moderate or severe WM echogenicity on US had a PP of 0.54 (0.42-0.66) for the presence of small petechial WM hemorrhage and/or diffuse excessive high-signal intensity (DEHSI) in the WM on T2-weighted images on MRI. However, mild/moderate or severe WM echogenicity on US scans performed at >/=7 days after birth had a PP of 0.72 (0.58-0.87) for the presence of WM hemorrhage and/or DEHSI on MRI. There were no cases of cystic periventricular leukomalacia., Conclusion: US accurately predicted the presence of GLH, IVH, and hemorrhagic parenchymal infarction on MRI. However, its ability to predict the presence of DEHSI and small petechial hemorrhages in the WM on T2 weighted images is not as good, but improves on scans performed at >/=7 days after birth. In addition, normal WM echogenicity on US is not a good predictor of normal WM signal intensity on MRI.
- Published
- 2001
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15. Pilot study of treatment with whole body hypothermia for neonatal encephalopathy.
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Azzopardi D, Robertson NJ, Cowan FM, Rutherford MA, Rampling M, and Edwards AD
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- Asphyxia Neonatorum blood, Asphyxia Neonatorum complications, Asphyxia Neonatorum physiopathology, Blood Viscosity, Body Temperature, Brain Diseases etiology, Electroencephalography, Hemodynamics, Humans, Infant, Newborn, Pilot Projects, Treatment Outcome, Asphyxia Neonatorum therapy, Brain Diseases prevention & control, Hypothermia, Induced adverse effects
- Abstract
Background: There is extensive experimental evidence to support the investigation of treatment with mild hypothermia after birth asphyxia. However, clinical studies have been delayed by the difficulty in predicting long-term outcome very soon after birth and by concern about adverse effects of hypothermia., Objectives: The objectives of this study were to determine whether it is feasible to select infants with a bad neurological prognosis and to begin hypothermic therapy within 6 hours of birth, and to observe the effect of this therapy on relevant physiologic variables., Methods: Sixteen newborn infants with clinical features of birth asphyxia (median cord blood pH: 6.74; range: 6.58-7.08) were assessed by amplitude integrated electroencephalography (aEEG), and mild whole body hypothermia was instituted within 6 hours of birth in the 10 infants with an aEEG prognostic of a bad outcome. Rectal temperature was maintained at 33.2 +/- (standard deviation).6 degrees C for 48 hours. Rectal and tympanic membrane temperature, blood pressure, heart rate, blood gases, blood lactate, full blood count, blood electrolytes, high and low shear rate viscosity, and coagulation studies were monitored during and after cooling. A preliminary assessment of neurological outcome was made by repeated magnetic resonance imaging (MRI) and neurological examination., Results: All infants selected to receive hypothermia developed convulsions and a severe encephalopathy. During 48 hours of hypothermia infants had prolonged metabolic acidosis (median pH: 7.30; base excess: -6.3 mmol x L(-1), a high blood lactate (median lactate: 5.3 mmol x L(-1)) and low blood potassium levels (median value: 3.9 mmol x L(-1)) x Hypothermia was associated with lower heart rate and higher mean blood pressure. However, these changes did not seem to be clinically relevant and no significant complication of hypothermia was encountered. Blood viscosity and coagulation studies were similar during and after cooling. Unusual MRI findings were noted in 3 infants: transverse sinus thrombosis with subsequent small cerebellar infarct; probable thrombosis in the straight sinus; and hemorrhagic cerebral infarction. Six of the 10 cooled infants had minor abnormalities only or normal follow-up neurological examination; 3 infants died and 1 had major abnormalities. None of the 6 infants with a normal aEEG developed severe neonatal encephalopathy or neurological sequel., Conclusions: After birth asphyxia infants can be objectively selected by aEEG and hypothermia started within 6 hours of birth in infants at high risk of developing severe neonatal encephalopathy. Prolonged mild hypothermia to 33 degrees C to 34 degrees C is associated with minor physiologic abnormalities. Further studies of both the safety and efficacy of mild hypothermia, including further neuroimaging studies, are warranted.
- Published
- 2000
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16. Magnetic resonance imaging of intestinal necrosis in preterm infants.
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Maalouf EF, Fagbemi A, Duggan PJ, Jayanthi S, Counsell SJ, Lewis HJ, Fletcher AM, Lakhoo K, and Edwards AD
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- Birth Weight, Colon pathology, Enterocolitis, Necrotizing surgery, Female, Gestational Age, Humans, Infant, Newborn, Male, Patient Care Planning, Risk Factors, Sensitivity and Specificity, Enterocolitis, Necrotizing diagnosis, Magnetic Resonance Imaging
- Abstract
Background and Objective: Noninvasive diagnosis of intestinal necrosis is important in planning surgery in preterm infants with necrotizing enterocolitis (NEC). We aimed to assess the potential of magnetic resonance imaging (MRI) for the diagnosis of intestinal necrosis., Study Participants and Methods: Abdominal MRI scans were performed in a group of preterm infants with suspected NEC and compared with surgical findings and to MRI results in a group of control infants. In addition, MRI was performed in 2 preterm infants with suspected NEC who did not require surgery., Results: Six infants with a median birth weight of 1220 g (range, 760-1770 g) and median gestational age at birth of 30 weeks (range, 28-34 weeks) were studied at a median postnatal age of 10 days (range, 4-19 days). Four infants had a bubble-like appearance in part of the intestinal wall, intramural gas, and an abnormal fluid level within bowel lumen. At surgery, NEC was found in 5 infants and sigmoid volvulus in 1. The site of the bubble-like appearance corresponded to the site of intestinal necrosis at surgery. Four control infants with a median birth weight of 1500 g (range, 730-2130 g) and a median gestational age of 31 weeks (range, 26-36 weeks) had abdominal MRI at a median postnatal age of 8 days (range, 4-70 days). None of the above findings were seen in any control infant. The bubble-like appearance was not seen in the 2 infants with suspected NEC who did not require surgery., Conclusion: Abdominal MRI allows the noninvasive diagnosis of bowel necrosis. This may aid the timing of surgical intervention in preterm infants with a clinical diagnosis of NEC.gangrene, ischemia, MRI, necrotizing enterocolitis.
- Published
- 2000
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17. Assessment of neonatal encephalopathy by amplitude-integrated electroencephalography.
- Author
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al Naqeeb N, Edwards AD, Cowan FM, and Azzopardi D
- Subjects
- Asphyxia Neonatorum diagnosis, Asphyxia Neonatorum etiology, Brain Diseases complications, Brain Diseases epidemiology, Electroencephalography, Female, Follow-Up Studies, Gestational Age, Humans, Infant, Newborn, Magnetic Resonance Imaging, Male, Neurologic Examination, Observer Variation, Predictive Value of Tests, Brain Diseases diagnosis
- Abstract
Objective: To define normal and abnormal patterns, test interobserver variability, and the prognostic accuracy of amplitude-integrated electroencephalography (aEEG) soon after the onset of neonatal encephalopathy., Methods: Consecutive cases of neonatal encephalopathy (n = 56; gestation median, 40; range, 35-42 weeks) and healthy infants (n = 14; gestation median, 40; range, 39-40 weeks) were studied. aEEG was recorded using a cerebral function monitor, at median, 0, range, 0-21 days of age. Of the infants, 24 of the 56 with encephalopathy and all of the normal infants were studied within 12 hours of birth (median, 5; range, 3-12 hours). Forty infants were suspected of having suffered birth asphyxia. Criteria for normal and abnormal patterns were defined and the interobserver variability of these classifications determined. Results were compared with neurodevelopmental outcome assessed at 18 to 24 months of age. aEEG also was compared with a standard EEG and with magnetic resonance imaging., Results: The median upper margin of the widest band of aEEG activity in the control infants was 37.5 microV (range, 30-48 microV), and median lower margin was 8 microV (range, 6.5-11 microV). We classified the aEEG background activity as normal amplitude, the upper margin of band of aEEG activity >10 microV and the lower margin >5 microV; moderately abnormal amplitude, the upper margin of band of aEEG activity >10 microV and the lower margin =5 microV; and suppressed amplitude, the upper margin of the band of aEEG activity <10 microV and lower margin <5 microV. Recordings were analyzed further for the presence of seizures, defined as periods of sudden increase in voltage accompanied by a narrowing of the band of aEEG activity. Tests of interobserver variability showed excellent agreement both for assessment of amplitude (kappa statistic = 0.85) and for identification of seizures (kappa statistic = 0.76) There was a close relationship between the aEEG and subsequent outcome: 19 of 21 infants with a normal aEEG finding were normal on follow-up at 18 to 24 months of age, whereas 27 of 35 infants with a moderately abnormal or suppressed aEEG and/or seizures died or developed neurologic abnormalities. Thus, aEEG predicted outcome with a sensitivity of 0. 93, a specificity of 0.70, positive predictive value of 0.77, negative predictive value of 0.90, and the likelihood ratio of a positive result of 3.1 and a negative result of 0.06. For the 24 infants studied within 12 hours of birth, the corresponding results were sensitivity, 1.0; specificity, 0.82; positive predictive value, 0.85; negative predictive value, 1; likelihood ratio of a positive result, 5.5; and likelihood ratio of a negative result, 0.18., Conclusion: The aEEG is a simple but accurate and reproducible clinical tool that could be useful in the assessment of infants with encephalopathy.
- Published
- 1999
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18. Abnormal magnetic resonance signal in the internal capsule predicts poor neurodevelopmental outcome in infants with hypoxic-ischemic encephalopathy.
- Author
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Rutherford MA, Pennock JM, Counsell SJ, Mercuri E, Cowan FM, Dubowitz LM, and Edwards AD
- Subjects
- Basal Ganglia pathology, Cerebral Cortex pathology, Dominance, Cerebral physiology, Female, Follow-Up Studies, Humans, Infant, Infant, Newborn, Male, Neurologic Examination, Sensitivity and Specificity, Thalamus pathology, Brain pathology, Brain Damage, Chronic diagnosis, Brain Ischemia diagnosis, Developmental Disabilities diagnosis, Hypoxia, Brain diagnosis, Magnetic Resonance Imaging
- Abstract
Objective: The aim of this study was to establish whether abnormal signal intensity in the posterior limb of the internal capsule (PLIC) on magnetic resonance imaging is an accurate predictor of neurodevelopmental outcome at 1 year of age in infants with hypoxic-ischemic encephalopathy (HIE)., Methods: We have examined 73 term neonates with HIE between 1 and 17 days after birth with cranial magnetic resonance imaging and related the magnetic resonance imaging findings to neurodevelopmental outcome at 1 year of age., Results: All infants with an abnormal signal intensity in the PLIC developed neurodevelopmental impairment although in 4 infants with very early scans the abnormal signal was not apparent until up to 4 days after birth. A normal signal intensity was associated with a normal outcome in all but 4 cases; 3 of these infants had minor impairments and all had persistent imaging changes within the white matter. The 4th infant with a normal signal intensity on day 2 died before a further image could be obtained. The absence of normal signal predicted abnormal outcome in term infants with HIE with a sensitivity of 0.90, a specificity of 1.0, a positive predictive value of 1.0, and a negative predictive value of 0.87. The test correctly predicted outcome in 93% of infants with grade II HIE, according to the Sarnat system. Applying a Bayesian approach, the predictive probability of the test (the probability that the test would predict an outcome correctly) was distributed with a mean of 0.94 and 95% confidence limits of 0.89 to 1.0., Conclusion: Abnormal signal intensity in the PLIC is an accurate predictor of neurodevelopmental outcome in term infants suffering HIE.
- Published
- 1998
- Full Text
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19. Magnetic resonance imaging of the brain in very preterm infants: visualization of the germinal matrix, early myelination, and cortical folding.
- Author
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Battin MR, Maalouf EF, Counsell SJ, Herlihy AH, Rutherford MA, Azzopardi D, and Edwards AD
- Subjects
- Brain physiology, Cerebral Cortex anatomy & histology, Cerebral Cortex physiology, Cerebral Ventricles anatomy & histology, Cerebral Ventricles physiology, Gestational Age, Humans, Infant, Newborn, Nerve Fibers, Myelinated, Brain anatomy & histology, Infant, Premature physiology, Magnetic Resonance Imaging
- Abstract
Objective: To investigate preterm infants, we have installed in our neonatal intensive care unit a dedicated magnetic resonance (MR) imaging system which was specifically designed for neonatal use. The aim of this study was to describe the MR appearances of the brain in preterm infants who were first scanned between 25 and 32 weeks gestational age (GA) and to outline changes to the brains of these infants between their first scan and term., Methods: Preterm infants of 25 to 32 weeks GA were imaged using the 1T neonatal MR system (Oxford Magnet Technology, Eyensham, Oxfordshire, England/Picker International, Cleveland, OH). The scanning protocol included T1-weighted conventional spin echo (repetition time [TR], 600; echo time, 20 ms), inversion recovery fast spin echo (TR, 3530; effective echo time, 30; inversion time, 950 ms), and T2-weighted fast spin echo (TR, 3500; effective echo time, 208 ms) sequences., Results: Seventeen infants of median 28 weeks GA (range, 24 to 31 weeks) at birth were imaged a total of 53 times between birth and term. The median number of images per infant was two (range, 1 to 9). In infants of < 30 weeks GA, the germinal matrix was visualized at the margins of the lateral ventricles. It had a short T1 and short T2 and the bulk of it involuted at between 30 and 32 weeks GA. The white matter had a relatively homogeneous low signal except for bands of altered signal (probably originating from regions containing radial glia and migrating cells) which were most apparent anterolateral and posterolateral to the lateral ventricles. Myelination was seen in the posterior brainstem, cerebellum, and region of the ventrolateral nuclei of the thalamus. Infants had very little cortical folding at 25 weeks GA but this developed later in an orderly fashion., Conclusion: The neonatal MR system allowed extremely preterm infants to be studied safely with MR imaging. The images acquired demonstrated the germinal matrix, early myelination, and early cortical folding. Evolution of these features was demonstrated with serial studies.
- Published
- 1998
- Full Text
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