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Clinics in Perinatology Sep 2022According to the World Health Organization (WHO), 15 million babies are born preterm each year. Preterm infants are those born at less than 37 weeks, while extremely... (Review)
Review
According to the World Health Organization (WHO), 15 million babies are born preterm each year. Preterm infants are those born at less than 37 weeks, while extremely and very preterm neonates include those born at 22 to less than 32 weeks gestational age. Infants that fail to make it to term are missing a key part in neurodevelopment, as weeks 24 to 40 are a critical period of brain development. Neonatal brain injury is a crucial predictor for mortality and morbidity in premature and low birth weight (<1500 g) infants. Although the complications associated with preterm birth continue to be the number one cause of death in children under 5, the survival rates are increasing (Volpe, 2019). Despite this, the incidence of comorbidities, such as learning disabilities and visual and hearing problems, is still high. The functional deficits seen in these infants can be contributed to the white matter abnormalities (WMA) that have been found in 50% to 80% of extremely and very preterm neonates. While numerous, the etiology of the neonatal brain injury is essential for determining the mortality and morbidities of the infant, as there is an increased risk for both intraventricular hemorrhage (IVH) and periventricular leukomalacia (PVL), which can be attributed to their lack of cerebrovascular autoregulation and hypoxic events. Neuroimaging plays a key role in detecting and assessing these neurologic injuries that preterm infants are at risk for. It is essential to diagnose these events early on to assess neurologic damage, minimize disease progression, and provide supportive care. Brain MRI and cranial ultrasound (CUS) are both extensively used neuroimaging techniques to assess WMA, and it has become ever more important to determine the best imaging techniques and modalities with the increasing survival rates and high incidence of comorbidities among these infants.
Topics: Brain Injuries; Child; Female; Humans; Infant; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Premature Birth
PubMed: 36113927
DOI: 10.1016/j.clp.2022.06.001 -
Journal of Pediatric Neurosciences 2017Neonatal hypoxic-ischemic encephalopathy (HIE) is a devastating condition that may result in death or severe neurologic deficits in children. Neuroimaging with cranial... (Review)
Review
Neonatal hypoxic-ischemic encephalopathy (HIE) is a devastating condition that may result in death or severe neurologic deficits in children. Neuroimaging with cranial ultrasound (US), computed tomography and magnetic resonance imaging are valuable tools in the workup of patients with HIE. The pattern of brain injury depends on the severity and duration of hypoxia and degree of brain maturation. Mild to moderate HI injury results in periventricular leukomalacia and germinal matrix bleed in preterm neonates, and parasagittal watershed infarcts in full-term neonates. Severe HI injury involves deep gray matter in both term and preterm infants. Treatment of HIE is largely supportive. The current article reviews the etiopathophysiology and clinical manifestations of HIE, role of imaging in the evaluation of the condition, patterns of brain injury in term and preterm neonates, the treatment and the prognosis.
PubMed: 28553370
DOI: 10.4103/1817-1745.205646 -
Journal of Child Neurology Feb 2022Periventricular leukomalacia (PVL) is a term reserved to describe white matter injury in the premature brain. In this review article, the authors highlight the common...
AIM
Periventricular leukomalacia (PVL) is a term reserved to describe white matter injury in the premature brain. In this review article, the authors highlight the common and rare pathologies mimicking the chronic stage of PVL and propose practical clinico-radiological criteria that would aid in diagnosis and management.
METHODS AND RESULTS
The authors first describe the typical brain MRI (magnetic resonance imaging) features of PVL. Based on their clinical presentation, pathologic entities and their neuroimaging findings were clustered into distinct categories. Three clinical subgroups were identified: healthy children, children with stable/nonprogressive neurological disorder, and those with progressive neurological disorder. The neuroradiological discriminators are described in each subgroup with relevant differential diagnoses. The mimics were broadly classified into normal variants, acquired, and inherited disorders.
CONCLUSIONS
The term "PVL" should be used appropriately as it reflects its pathomechanism. The phrase "white matter injury of prematurity" or "brain injury of prematurity" is more specific. Discrepancies in imaging and clinical presentation must be tread with caution and warrant further investigations to exclude other possibilities.
Topics: Brain; Cerebral Palsy; Female; Gestational Age; Humans; Infant, Newborn; Leukomalacia, Periventricular; Magnetic Resonance Imaging; Male; Pregnancy; Pregnancy Complications; Risk Factors
PubMed: 34937403
DOI: 10.1177/08830738211026052 -
Clinics in Perinatology Jun 2018Perinatal brain injury may lead to long-term morbidity and neurodevelopmental impairment. Improvements in perinatal care have resulted in the survival of more infants... (Review)
Review
Perinatal brain injury may lead to long-term morbidity and neurodevelopmental impairment. Improvements in perinatal care have resulted in the survival of more infants with perinatal brain injury. The effects of hypoxia-ischemia, inflammation, and infection during critical periods of development can lead to a common pathway of perinatal brain injury marked by neuronal excitotoxicity, cellular apoptosis, and microglial activation. Various interventions can prevent or improve the outcomes of different types of perinatal brain injury. The objective of this article is to review the mechanisms of perinatal brain injury, approaches to prevention, and outcomes among children with perinatal brain injury.
Topics: Adrenal Cortex Hormones; Brain Injuries; Combined Modality Therapy; Female; Gestational Age; Humans; Hypothermia, Induced; Hypoxia-Ischemia, Brain; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Intracranial Hemorrhages; Leukomalacia, Periventricular; Magnetic Resonance Imaging; Male; Neuroprotective Agents; Perinatal Care; Pregnancy; Prognosis; Survival Analysis; Treatment Outcome
PubMed: 29747893
DOI: 10.1016/j.clp.2018.01.015 -
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 -
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 -
Biomedicines Dec 2022We asked whether hyperoxia might induce hypomyelination of the corpus callosum, clinically described as periventricular leukomalacia (PVL) of the severely preterm...
We asked whether hyperoxia might induce hypomyelination of the corpus callosum, clinically described as periventricular leukomalacia (PVL) of the severely preterm infant. Mouse pups and their nursing dams were placed in 80% oxygen from P4-P8, then removed to room air until P11. Corpus callosal sections were probed myelin immunofluorescence, tested for myelin basic protein concentration by Western blot, and both glial fibrillary acidic protein levels and apoptosis quantified. Density of corpus callosal capillaries were measured after lectin staining and hypoxia measured by Hypoxyprobe. Numbers of oligodendrocytes were quantified by immunohistochemistry. We next used hypoxiamimesis as a surrogate to hypoxia by comparing cerebral hypoxia inducible factor (HIF) stabilization to hepatic HIF stabilization. Hyperoxia induced hypomyelination and a reduction of corpus callosal capillaries. Hyperoxia decreased numbers of oligodendrocytes with an increase in corpus callosal fibrosis and apoptosis. Cerebral hypoxiamimesis induced hypomyelination whereas hepatic hypoxiamimesis alone increased myelination, oligodendrocyte numbers, and corpus callosal capillary density. Hepatic HIF-1 dependence on myelination was confirmed using the cre/lox hepatic HIF-1 knockout. These findings suggest that hyperoxia can induce hypomyelination through vasoobliteration and subsequent ischemia, adding a potential oxygen induced mechanism to the diverse causes of periventricular leukomalacia of the severely preterm infant. Targeting hepatic HIF-1 alone led to increased myelination.
PubMed: 36672545
DOI: 10.3390/biomedicines11010037 -
Brain and Nerve = Shinkei Kenkyu No... Jun 2022Cerebral palsy (CP) is a relatively common neurological disease, and its prevalence at a transitional age is estimated to be approximately 0.2% in Japan. We should...
Cerebral palsy (CP) is a relatively common neurological disease, and its prevalence at a transitional age is estimated to be approximately 0.2% in Japan. We should understand the pathology of CP, which causes various dysfunctions other than motor disturbances, for delivering a comprehensive treatment. Rapid progress in perinatal medicine has altered the underlying brain lesions. Bilateral spastic CP associated with visual cognitive impairment due to periventricular leukomalacia has becomethe most prevalent instead of dyskinetic CP due to kernicterus. New types of brain lesions found in very premature infants will be more common among adult CP in the future. Cerebellar injury causes disturbances in cognition and communication, and bilirubin encephalopathy causes severe motor impairment with marked dystonia. The latter needs various medical treatments, including botulinum toxin and intrathecal baclofen. Elevated risk of lifestyle-related and psychological diseases should also be considered.
Topics: Adult; Cerebral Palsy; Cognitive Dysfunction; Female; Humans; Infant; Japan; Pregnancy
PubMed: 35676210
DOI: 10.11477/mf.1416202117