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Pediatric Research Mar 2020White matter injury (WMI) is the most frequent form of preterm brain injury. Cranial ultrasound (CUS) remains the preferred modality for initial and sequential... (Review)
Review
White matter injury (WMI) is the most frequent form of preterm brain injury. Cranial ultrasound (CUS) remains the preferred modality for initial and sequential neuroimaging in preterm infants, and is reliable for the diagnosis of cystic periventricular leukomalacia. Although magnetic resonance imaging is superior to CUS in detecting the diffuse and more subtle forms of WMI that prevail in very premature infants surviving nowadays, recent improvement in the quality of neonatal CUS imaging has broadened the spectrum of preterm white matter abnormalities that can be detected with this technique. We propose a structured CUS assessment of WMI of prematurity that seeks to account for both cystic and non-cystic changes, as well as signs of white matter loss and impaired brain growth and maturation, at or near term equivalent age. This novel assessment system aims to improve disease description in both routine clinical practice and clinical research. Whether this systematic assessment will improve prediction of outcome in preterm infants with WMI still needs to be evaluated in prospective studies.
Topics: Brain; Brain Injuries; Echoencephalography; Humans; Infant; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Leukomalacia, Periventricular; Magnetic Resonance Imaging; Neonatology; Predictive Value of Tests; White Matter
PubMed: 32218534
DOI: 10.1038/s41390-020-0781-1 -
Acta Neuropathologica Sep 2017The human preterm brain is particularly susceptible to cerebral white matter injury (WMI) that disrupts the normal progression of developmental myelination. Advances in... (Review)
Review
The human preterm brain is particularly susceptible to cerebral white matter injury (WMI) that disrupts the normal progression of developmental myelination. Advances in the care of preterm infants have resulted in a sustained reduction in the severity of WMI that has shifted from more severe focal necrotic lesions to milder diffuse WMI. Nevertheless, WMI remains a global health problem and the most common cause of chronic neurological morbidity from cerebral palsy and diverse neurobehavioral disabilities. Diffuse WMI involves maturation-dependent vulnerability of the oligodendrocyte (OL) lineage with selective degeneration of late oligodendrocyte progenitors (preOLs) triggered by oxidative stress and other insults. The magnitude and distribution of diffuse WMI are related to both the timing of appearance and regional distribution of susceptible preOLs. Diffuse WMI disrupts the normal progression of OL lineage maturation and myelination through aberrant mechanisms of regeneration and repair. PreOL degeneration is accompanied by early robust proliferation of OL progenitors that regenerate and augment the preOL pool available to generate myelinating OLs. However, newly generated preOLs fail to differentiate and initiate myelination along their normal developmental trajectory despite the presence of numerous intact-appearing axons. Disrupted preOL maturation is accompanied by diffuse gliosis and disturbances in the composition of the extracellular matrix and is mediated in part by inhibitory factors derived from reactive astrocytes. Signaling pathways implicated in disrupted myelination include those mediated by Notch, WNT-beta catenin, and hyaluronan. Hence, there exists a potentially broad but still poorly defined developmental window for interventions to promote white matter repair and myelination and potentially reverses the widespread disturbances in cerebral gray matter growth that accompanies WMI.
Topics: Brain; Humans; Infant, Newborn; Infant, Premature; Leukomalacia, Periventricular; Nerve Fibers, Myelinated; Neuroglia; White Matter
PubMed: 28534077
DOI: 10.1007/s00401-017-1718-6 -
Pediatrics Jul 2021The National Institute of Child Health and Human Development Neonatal Research Network recently proposed new, severity-based diagnostic criteria for bronchopulmonary...
BACKGROUND AND OBJECTIVES
The National Institute of Child Health and Human Development Neonatal Research Network recently proposed new, severity-based diagnostic criteria for bronchopulmonary dysplasia (BPD). This study provides the first benchmark epidemiological data applying this definition.
METHODS
Retrospective cohort study of infants born from 22 to 29 weeks' gestation in 2018 at 715 US hospitals in the Vermont Oxford Network. Rates of BPD, major neonatal morbidities, and common respiratory therapies, stratified by BPD severity, were determined.
RESULTS
Among 24 896 infants, 2574 (10.3%) died before 36 weeks' postmenstrual age (PMA), 12 198 (49.0%) did not develop BPD, 9192 (36.9%) developed grade 1 or 2 BPD, and 932 (3.7%) developed grade 3 BPD. Rates of mortality before 36 weeks' PMA and grade 3 BPD decreased from 52.7% and 9.9%, respectively, among infants born at 22 weeks' gestation to 17.3% and 0.8% among infants born at 29 weeks' gestation. Grade 1 or 2 BPD peaked in incidence (51.8%) among infants born at 25 weeks' gestation. The frequency of severe intraventricular hemorrhage or cystic periventricular leukomalacia increased from 4.8% among survivors without BPD to 23.4% among survivors with grade 3 BPD. Similar ranges were observed for late onset sepsis (4.8%-31.4%), surgically treated necrotizing enterocolitis (1.4%-17.1%), severe retinopathy of prematurity (1.2%-23.0%), and home oxygen therapy (2.0%-67.5%).
CONCLUSIONS
More than one-half of very preterm infants born in the United States died before 36 weeks' PMA or developed BPD. Greater BPD severity was associated with more frequent development of major neonatal morbidities, in-hospital mortality, and use of supplemental respiratory support at discharge.
Topics: Bronchopulmonary Dysplasia; Cerebral Intraventricular Hemorrhage; Gestational Age; Humans; Incidence; Infant; Infant, Newborn; Infant, Premature; Leukomalacia, Periventricular; Retrospective Studies; Severity of Illness Index; Vermont
PubMed: 34078747
DOI: 10.1542/peds.2020-030007 -
The Lancet. Neurology Jan 2009Brain injury in premature infants is of enormous public health importance because of the large number of such infants who survive with serious neurodevelopmental... (Review)
Review
Brain injury in premature infants is of enormous public health importance because of the large number of such infants who survive with serious neurodevelopmental disability, including major cognitive deficits and motor disability. This type of brain injury is generally thought to consist primarily of periventricular leukomalacia (PVL), a distinctive form of cerebral white matter injury. Important new work shows that PVL is frequently accompanied by neuronal/axonal disease, affecting the cerebral white matter, thalamus, basal ganglia, cerebral cortex, brain stem, and cerebellum. This constellation of PVL and neuronal/axonal disease is sufficiently distinctive to be termed "encephalopathy of prematurity". The thesis of this Review is that the encephalopathy of prematurity is a complex amalgam of primary destructive disease and secondary maturational and trophic disturbances. This Review integrates the fascinating confluence of new insights into both brain injury and brain development during the human premature period.
Topics: Axons; Brain; Brain Injuries; Developmental Disabilities; Humans; Infant, Newborn; Infant, Premature; Leukomalacia, Periventricular; Neurons
PubMed: 19081519
DOI: 10.1016/S1474-4422(08)70294-1 -
JAMA Sep 2015Extremely preterm infants contribute disproportionately to neonatal morbidity and mortality.
IMPORTANCE
Extremely preterm infants contribute disproportionately to neonatal morbidity and mortality.
OBJECTIVE
To review 20-year trends in maternal/neonatal care, complications, and mortality among extremely preterm infants born at Neonatal Research Network centers.
DESIGN, SETTING, PARTICIPANTS
Prospective registry of 34,636 infants, 22 to 28 weeks' gestation, birth weight of 401 to 1500 g, and born at 26 network centers between 1993 and 2012.
EXPOSURES
Extremely preterm birth.
MAIN OUTCOMES AND MEASURES
Maternal/neonatal care, morbidities, and survival. Major morbidities, reported for infants who survived more than 12 hours, were severe necrotizing enterocolitis, infection, bronchopulmonary dysplasia, severe intracranial hemorrhage, cystic periventricular leukomalacia, and/or severe retinopathy of prematurity. Regression models assessed yearly changes and were adjusted for study center, race/ethnicity, gestational age, birth weight for gestational age, and sex.
RESULTS
Use of antenatal corticosteroids increased from 1993 to 2012 (24% [348 of 1431 infants]) to 87% (1674 of 1919 infants]; P < .001), as did cesarean delivery (44% [625 of 1431 births] to 64% [1227 of 1921]; P < .001). Delivery room intubation decreased from 80% (1144 of 1433 infants) in 1993 to 65% (1253 of 1922) in 2012 (P < .001). After increasing in the 1990s, postnatal steroid use declined to 8% (141 of 1757 infants) in 2004 (P < .001), with no significant change thereafter. Although most infants were ventilated, continuous positive airway pressure without ventilation increased from 7% (120 of 1666 infants) in 2002 to 11% (190 of 1756 infants) in 2012 (P < .001). Despite no improvement from 1993 to 2004, rates of late-onset sepsis declined between 2005 and 2012 for infants of each gestational age (median, 26 weeks [37% {109 of 296} to 27% {85 of 320}]; adjusted relative risk [RR], 0.93 [95% CI, 0.92-0.94]). Rates of other morbidities declined, but bronchopulmonary dysplasia increased between 2009 and 2012 for infants at 26 to 27 weeks' gestation (26 weeks, 50% [130 of 258] to 55% [164 of 297]; P < .001). Survival increased between 2009 and 2012 for infants at 23 weeks' gestation (27% [41 of 152] to 33% [50 of 150]; adjusted RR, 1.09 [95% CI, 1.05-1.14]) and 24 weeks (63% [156 of 248] to 65% [174 of 269]; adjusted RR, 1.05 [95% CI, 1.03-1.07]), with smaller relative increases for infants at 25 and 27 weeks' gestation, and no change for infants at 22, 26, and 28 weeks' gestation. Survival without major morbidity increased approximately 2% per year for infants at 25 to 28 weeks' gestation, with no change for infants at 22 to 24 weeks' gestation.
CONCLUSIONS AND RELEVANCE
Among extremely preterm infants born at US academic centers over the last 20 years, changes in maternal and infant care practices and modest reductions in several morbidities were observed, although bronchopulmonary dysplasia increased. Survival increased most markedly for infants born at 23 and 24 weeks' gestation and survival without major morbidity increased for infants aged 25 to 28 weeks. These findings may be valuable in counseling families and developing novel interventions.
TRIAL REGISTRATION
clinicaltrials.gov Identifier: NCT00063063.
Topics: Adrenal Cortex Hormones; Adult; Bronchopulmonary Dysplasia; Cesarean Section; Continuous Positive Airway Pressure; Enterocolitis, Necrotizing; Female; Gestational Age; Humans; Infant, Extremely Premature; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infections; Intensive Care, Neonatal; Intracranial Hemorrhages; Leukomalacia, Periventricular; Male; Pregnancy; Retinopathy of Prematurity; Survival Analysis; United States
PubMed: 26348753
DOI: 10.1001/jama.2015.10244 -
Genetics in Medicine : Official Journal... Nov 2015Two proα1(IV) chains, encoded by COL4A1, form trimers that contain, in addition, a proα2(IV) chain encoded by COL4A2 and are the major component of the basement... (Meta-Analysis)
Meta-Analysis Review
Two proα1(IV) chains, encoded by COL4A1, form trimers that contain, in addition, a proα2(IV) chain encoded by COL4A2 and are the major component of the basement membrane in many tissues. Since 2005, COL4A1 mutations have been known as an autosomal dominant cause of hereditary porencephaly. COL4A1 and COL4A2 mutations have been reported with a broader spectrum of cerebrovascular, renal, ophthalmological, cardiac, and muscular abnormalities, indicated as "COL4A1 mutation-related disorders." Genetic counseling is challenging because of broad phenotypic variation and reduced penetrance. At the Erasmus University Medical Center, diagnostic DNA analysis of both COL4A1 and COL4A2 in 183 index patients was performed between 2005 and 2013. In total, 21 COL4A1 and 3 COL4A2 mutations were identified, mostly in children with porencephaly or other patterns of parenchymal hemorrhage, with a high de novo mutation rate of 40% (10/24). The observations in 13 novel families harboring either COL4A1 or COL4A2 mutations prompted us to review the clinical spectrum. We observed recognizable phenotypic patterns and propose a screening protocol at diagnosis. Our data underscore the importance of COL4A1 and COL4A2 mutations in cerebrovascular disease, also in sporadic patients. Follow-up data on symptomatic and asymptomatic mutation carriers are needed for prognosis and appropriate surveillance.
Topics: Alleles; Anterior Eye Segment; Brain; Cerebral Hemorrhage; Cohort Studies; Collagen Type IV; Eye Abnormalities; Eye Diseases, Hereditary; Family; Gene Order; Genetic Association Studies; Genetic Loci; Genotype; Humans; Leukomalacia, Periventricular; Magnetic Resonance Imaging; Mutation; Pedigree; Phenotype; Porencephaly
PubMed: 25719457
DOI: 10.1038/gim.2014.210 -
Journal of the American Chemical Society Mar 2014Ferrostatin-1 (Fer-1) inhibits ferroptosis, a form of regulated, oxidative, nonapoptotic cell death. We found that Fer-1 inhibited cell death in cellular models of...
Ferrostatin-1 (Fer-1) inhibits ferroptosis, a form of regulated, oxidative, nonapoptotic cell death. We found that Fer-1 inhibited cell death in cellular models of Huntington's disease (HD), periventricular leukomalacia (PVL), and kidney dysfunction; Fer-1 inhibited lipid peroxidation, but not mitochondrial reactive oxygen species formation or lysosomal membrane permeability. We developed a mechanistic model to explain the activity of Fer-1, which guided the development of ferrostatins with improved properties. These studies suggest numerous therapeutic uses for ferrostatins, and that lipid peroxidation mediates diverse disease phenotypes.
Topics: Cell Death; Cyclohexylamines; Huntington Disease; Kidney Diseases; Leukomalacia, Periventricular; Lipid Peroxidation; Membrane Lipids; Oxidation-Reduction; Phenylenediamines
PubMed: 24592866
DOI: 10.1021/ja411006a -
Archives of Neurology Oct 2008Periventricular leukomalacia (PVL) is the predominant form of brain injury and the leading known cause of cerebral palsy and cognitive deficits in premature infants. The... (Review)
Review
Periventricular leukomalacia (PVL) is the predominant form of brain injury and the leading known cause of cerebral palsy and cognitive deficits in premature infants. The number of low-birth-weight infants who survive to demonstrate these neurologic deficts is increasing. Magnetic resonance imaging-based neuroimaging techniques provide greater diagnostic sensitivity for PVL than does head ultrasonography and often document the involvement of telencephalic gray matter and long tracts in addition to periventricular white matter. The neuropathologic hallmarks of PVL are microglial activation and focal and diffuse periventricular depletion of premyelinating oligodendroglia. Premyelinating oligodendroglia are highly vulnerable to death caused by glutamate, free radicals, and proinflammatory cytokines. Studies in animal models of PVL suggest that pharmacologic interventions that target these toxic molecules will be useful in diminishing the severity of PVL.
Topics: Animals; Brain; Encephalitis; Female; Gliosis; Humans; Infant, Newborn; Leukomalacia, Periventricular; Magnetic Resonance Imaging; Microglia; Nerve Fibers, Myelinated; Neural Pathways; Oligodendroglia; Oxidative Stress; Pregnancy
PubMed: 18852342
DOI: 10.1001/archneur.65.10.1291 -
Pediatric Research Mar 2020In the past three decades, cerebral ultrasound (CUS) has become a trusted technique to study the neonatal brain. It is a relatively cheap, non-invasive, bedside... (Review)
Review
In the past three decades, cerebral ultrasound (CUS) has become a trusted technique to study the neonatal brain. It is a relatively cheap, non-invasive, bedside neuroimaging method available in nearly every hospital. Traditionally, CUS was used to detect major abnormalities, such as intraventricular hemorrhage (IVH), periventricular hemorrhagic infarction, post-hemorrhagic ventricular dilatation, and (cystic) periventricular leukomalacia (cPVL). The use of different acoustic windows, such as the mastoid and posterior fontanel, and ongoing technological developments, allows for recognizing other lesion patterns (e.g., cerebellar hemorrhage, perforator stroke, developmental venous anomaly). The CUS technique is still being improved with the use of higher transducer frequencies (7.5-18 MHz), 3D applications, advances in vascular imaging (e.g. ultrafast plane wave imaging), and improved B-mode image processing. Nevertheless, the helpfulness of CUS still highly depends on observer skills, knowledge, and experience. In this special article, we discuss how to perform a dedicated state-of-the-art neonatal CUS, and we provide suggestions for structured reporting and quality assessment.
Topics: Animals; Asphyxia; Brain; Brain Diseases; Cerebral Hemorrhage; Cerebral Infarction; Echoencephalography; Humans; Hypoxia-Ischemia, Brain; Infant, Newborn; Infant, Newborn, Diseases; Infant, Premature; Infant, Premature, Diseases; Leukomalacia, Periventricular
PubMed: 32218539
DOI: 10.1038/s41390-020-0776-y -
Revista de Neurologia Nov 2014Visuospatial functions are very important in learning process and development of abstract thought during childhood. Several studies show that preterm and low birth... (Review)
Review
Visuospatial functions are very important in learning process and development of abstract thought during childhood. Several studies show that preterm and low birth weight infants obtain lower scores in test that assess cognitive functions, specially in the first year of life. These differences are attenuated over time, but a developmental delay that affects working memory and visuospatial process still persists. It is unclear what factors are involved in development of these functions, and pre- or perinatal factors may interfere with the proper conduct of the same, but have been described anatomical and physiological differences between the preterm and term brain that could explain somewhere in these alterations. The different selective vulnerability to hypoxia between immature brain in which preoligodendrocytes and subplate neurons predominate, and mature brain, determine differences in the pattern of injury from hypoxia with greater involvement of the periventricular white matter in preterm children. This lesional pattern leaves to a dysfunction in attentional and visuospatial process, due to the increased vulnerability of the regions involved in the dorsal pathway of visual processing.
Topics: Brain; Cognition Disorders; Fetal Hypoxia; Humans; Hypoxia, Brain; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Learning Disabilities; Leukomalacia, Periventricular; Nerve Net; Neurons; Oligodendroglia; Space Perception; Visual Pathways; Visual Perception
PubMed: 25342055
DOI: No ID Found