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PloS One 2017Although investigators have implicated hypoxic-ischemia (HI) as a potential cause of periventricular leukomalacia (PVL), the role of clinical risk factors or markers for... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Although investigators have implicated hypoxic-ischemia (HI) as a potential cause of periventricular leukomalacia (PVL), the role of clinical risk factors or markers for HI in the development of PVL remains controversial. The aim of this study was to identify perinatal HI-related factors associated with PVL.
METHOD
The PubMed, EMBASE, and Cochrane Library databases were searched. The last search was performed on January 2017. Summary effect estimates (pooled odds ratios [ORs]) were calculated for each risk factor using fixed or random effects models with tests for heterogeneity and publication bias.
RESULTS
Fifteen studies with a total of 12,851 participants were included in this meta-analysis, and 14 potential risk factors were analyzed. The pooled results showed that mothers with oligohydramnios (OR, 1.55; 95% confidence interval [CI], 1.05 to 2.30), preterm infants with acidemia (OR, 1.87; 95% CI, 1.18 to 2.97), 1-minute Apgar score <7 (OR 2.69; 95% CI, 1.13 to 6.41), 5-minute Apgar score <7 (OR, 1.89; 95% CI, 1.39 to 2.56), apnea (OR, 1.76; 95% CI, 1.07 to 2.90), respiratory distress syndrome (OR, 1.46; 95% CI, 1.04 to 2.03), and seizures (OR, 4.60; 95% CI, 2.84 to 7.46) were associated with increased risk of PVL.
CONCLUSION
This study identified perinatal HI-related risk factors for the development of PVL in preterm infants. Future large-scale prospective clinical studies are required to validate and extend these findings.
Topics: Female; Humans; Hypoxia-Ischemia, Brain; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Leukomalacia, Periventricular; Pregnancy; Risk Factors
PubMed: 28931047
DOI: 10.1371/journal.pone.0184993 -
Journal of Neurodevelopmental Disorders Aug 2023Leukomalacia is a serious form of neonatal brain injury that often leads to neurodevelopmental impairment, and studies on neonatal leukomalacia and its long-term...
BACKGROUND
Leukomalacia is a serious form of neonatal brain injury that often leads to neurodevelopmental impairment, and studies on neonatal leukomalacia and its long-term outcomes are lacking. The aim of this study was to analyze the clinical manifestations, imaging features, and long-term neurodevelopmental outcomes in preterm infants and term infants with leukomalacia.
METHODS
Newborns diagnosed with leukomalacia by head magnetic resonance imaging (MRI) and who were admitted to intensive care units from January 2015 to June 2020 were enrolled. All infants were followed up to June 2022 (2-7 years old), and their neurodevelopmental outcomes were evaluated. The clinical data and long- term outcomes of preterm infants and term infants was analyzed by Chi-square tests.
RESULTS
A total of 218 surviving infants with leukomalacia including 114 preterm infants and 104 term infants completed the follow-up. The major typesof leukomalacia on MRI were periventricular leukomalacia in the preterm group and subcortical cystic leukomalacia in the term group, respectively (χ = 55.166; p < 0.001). When followed up to 2-7 years old, the incidence of neurodevelopmental impairment in the preterm group and term group was not significantly different (χ = 0.917; p = 0.338). However, the incidence of cerebral palsy (CP) in the preterm group was significantly higher (χ = 4.896; p = 0.027), while the incidence of intellectual disability (ID) (χ = 9.445; p = 0.002), epilepsy (EP) (χ = 23.049; p < 0.001), and CP combined with ID andEP (χ = 4.122; p = 0.042) was significantly lower than that in the term group.
CONCLUSIONS
Periventricular leukomalacia mainly occurred in preterm infants while subcortical cystic leukomalacia was commonly seen in term infants. Although the long-term neurodevelopmental outcomes of leukomalacia were both poor, preterm infants were more prone to CP, while term infants were more prone to ID, EP, and the combination of CP with ID and EP.
Topics: Infant, Newborn; Infant; Humans; Child, Preschool; Child; Infant, Premature; Cohort Studies; Leukomalacia, Periventricular; Cerebral Palsy; Epilepsy
PubMed: 37550616
DOI: 10.1186/s11689-023-09489-7 -
International Journal of Molecular... Jun 2023Germinal matrix hemorrhage (GMH) is a pathology that occurs in infancy, with often devastating long-term consequences. Posthemorrhagic hydrocephalus (PHH) can develop...
Germinal matrix hemorrhage (GMH) is a pathology that occurs in infancy, with often devastating long-term consequences. Posthemorrhagic hydrocephalus (PHH) can develop acutely, while periventricular leukomalacia (PVL) is a chronic sequala. There are no pharmacological therapies to treat PHH and PVL. We investigated different aspects of the complement pathway in acute and chronic outcomes after murine neonatal GMH induced at postnatal day 4 (P4). Following GMH-induction, the cytolytic complement membrane attack complex (MAC) colocalized with infiltrating red blood cells (RBCs) acutely but not in animals treated with the complement inhibitor CR2-Crry. Acute MAC deposition on RBCs was associated with heme oxygenase-1 expression and heme and iron deposition, which was reduced with CR2-Crry treatment. Complement inhibition also reduced hydrocephalus and improved survival. Following GMH, there were structural alterations in specific brain regions linked to motor and cognitive functions, and these changes were ameliorated by CR2-Crry, as measured at various timepoints through P90. Astrocytosis was reduced in CR2-Crry-treated animals at chronic, but not acute, timepoints. At P90, myelin basic protein and LAMP-1 colocalized, indicating chronic ongoing phagocytosis of white matter, which was reduced by CR2-Crry treatment. Data indicate acute MAC-mediated iron-related toxicity and inflammation exacerbated the chronic effects of GMH.
Topics: Mice; Animals; Hydrocephalus; Complement System Proteins; Cerebral Hemorrhage; Inflammation; Complement Membrane Attack Complex; Iron; Recombinant Fusion Proteins
PubMed: 37373319
DOI: 10.3390/ijms241210171 -
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 -
Antioxidants (Basel, Switzerland) Dec 2021Free radicals play a role of paramount importance in the development of neonatal brain injury. Depending on the pathophysiological mechanisms underlying free radical... (Review)
Review
Free radicals play a role of paramount importance in the development of neonatal brain injury. Depending on the pathophysiological mechanisms underlying free radical overproduction and upon specific neonatal characteristics, such as the GA-dependent maturation of antioxidant defenses and of cerebrovascular autoregulation, different profiles of injury have been identified. The growing evidence on the detrimental effects of free radicals on the brain tissue has led to discover not only potential biomarkers for oxidative damage, but also possible neuroprotective therapeutic approaches targeting oxidative stress. While a more extensive validation of free radical biomarkers is required before considering their use in routine neonatal practice, two important treatments endowed with antioxidant properties, such as therapeutic hypothermia and magnesium sulfate, have become part of the standard of care to reduce the risk of neonatal brain injury, and other promising therapeutic strategies are being tested in clinical trials. The implementation of currently available evidence is crucial to optimize neonatal neuroprotection and to develop individualized diagnostic and therapeutic approaches addressing oxidative brain injury, with the final aim of improving the neurological outcome of this population.
PubMed: 34943115
DOI: 10.3390/antiox10122012 -
Journal of Clinical Neurology (Seoul,... Jan 2020
PubMed: 31942779
DOI: 10.3988/jcn.2020.16.1.172 -
Bioengineered Apr 2022Studies have shown that periventricular leukomalacia (PVL) is a distinctive form of cerebral white matter injury that pertains to myelination disturbances. Maternal...
Studies have shown that periventricular leukomalacia (PVL) is a distinctive form of cerebral white matter injury that pertains to myelination disturbances. Maternal inflammation is a main cause of white matter injury. Intrauterine inflammation cellular will be propagated to the developing brain by the entire maternal-placental-fetal axis, and triggers neural immune injury. As a low-affinity receptor, adenosine A receptor (AAR) requires high concentrations of adenosine to be significantly activated in pathological conditions. We hypothesized that in the maternal inflammation-induced PVL model, a selective AAR antagonist PSB0788 had the potential to prevent the injury. In this work, a total of 18 SD pregnant rats were divided into three groups, and treated with intraperitoneal injection of phosphate buffered saline (PBS), lipopolysaccharide (LPS), or LPS+PSB0788. Placental infection was determined by H&E staining and the inflammatory condition was determined by ELISA. Change of MBP, NG2 and CC-1 in the brain of the rats' offspring were detected by western blot and immunohistochemistry. Furthermore, LPS-induced maternal inflammation reduced the expression of MBP, which related to the decrease in the numbers of OPCs and mature oligodendrocytes in neonate rats. After treatment with PSB0788, the levels of MBP proteins increased in the rats' offspring, improved the remyelination. In conclusion, our study shows that the selective AAR antagonist PSB0788 plays an important role in promoting the normal development of OPCs by the maternal inflammation-induced PVL model. Future studies will focus on the mechanism of PSB0788 in this model.
Topics: Animals; Animals, Newborn; Brain; Brain Injuries; Disease Models, Animal; Female; Humans; Infant, Newborn; Inflammation; Leukomalacia, Periventricular; Lipopolysaccharides; Placenta; Pregnancy; Rats
PubMed: 35436416
DOI: 10.1080/21655979.2022.2061296 -
Journal of Child Neurology Sep 2009Intraventricular hemorrhage and cystic periventricular leukomalacia are often co-occurring characteristics of brain damage in preterm infants. Using data from 1016...
Intraventricular hemorrhage and cystic periventricular leukomalacia are often co-occurring characteristics of brain damage in preterm infants. Using data from 1016 infants born before 30 completed weeks' gestational age, we sought to clarify the relationship between severe intraventricular hemorrhage and cystic periventricular leukomalacia, with special emphasis on common antecedents and potential confounding. After comparing risk factors for intraventricular hemorrhage grades 1 through 4 and cystic periventricular leukomalacia, it appears the risk patterns for intraventricular hemorrhage grade 3, intraventricular hemorrhage grade 4, and cystic periventricular leukomalacia differ. The association between intraventricular hemorrhage grade 3 and cystic periventricular leukomalacia differs appreciably from the association between intraventricular hemorrhage grade 4 and cystic periventricular leukomalacia, supporting the notion that intraventricular hemorrhage grade 3 and intraventricular hemorrhage grade 4 are different entities. The presence of intraventricular hemorrhage grade 3 and intraventricular hemorrhage grade 4 increases the risk of cystic periventricular leukomalacia, even after adjusting for potential confounders. This raises the possibility that intraventricular hemorrhage grade 3 and intraventricular hemorrhage grade 4 cause cystic periventricular leukomalacia.
Topics: Cerebral Hemorrhage; Female; Gestational Age; Humans; Infant, Newborn; Infant, Premature; Leukomalacia, Periventricular; Logistic Models; Male; Odds Ratio; Premature Birth; Respiration; Retrospective Studies; Risk Factors
PubMed: 19745088
DOI: 10.1177/0883073809338064 -
Indian Journal of Ophthalmology Feb 2022Owing to the paucity of literature on Indian children with periventricular leukomalacia (PVL), this retrospective study aimed to describe the visual and associated...
PURPOSE
Owing to the paucity of literature on Indian children with periventricular leukomalacia (PVL), this retrospective study aimed to describe the visual and associated developmental abnormalities in a series of affected children attending a tertiary level eye care facility.
METHODS
Children with radiologically confirmed PVL who attended the Pediatric Department of a tertiary eye hospital were included and underwent a detailed ocular and general developmental assessment.
RESULTS
Of the 75 children, the mean age was 2.3 years, the mean follow-up was 3.1 years, 68% were males and 43% were born preterm. Grade I PVL was identified in 13 children (17%), Grade 2 PVL in 39 (52%), and Grade 3 PVL in 23 (31%). Premies with ≤2 kg (72.5%) and term babies with >2 kg (75%) had a greater association of PVL occurrence with a preponderance to severe PVL; 46% of the children were visually impaired which was significantly higher in the children with Grade 3 PVL (74%) than those with Grade 2 PVL (15%). Strabismus was common (80%) with a change in deviation over time. Seventy-one percent of the children had a refractive error, frequently myopic astigmatism. All the children except two had a delay in one or more general developmental milestones.
CONCLUSION
PVL occurrence is observed both in the babies born at term and premies, resulting in significant ocular and systemic morbidities. We recommend a system in place for early identification and referral to initiate an early intervention program which goes a long way toward improving the quality of life in these children.
Topics: Child; Child, Preschool; Humans; Infant; Infant, Newborn; Leukomalacia, Periventricular; Male; Quality of Life; Retrospective Studies; Strabismus
PubMed: 35086248
DOI: 10.4103/ijo.IJO_1779_21 -
Frontiers in Neurology 2023Brain injury is the main factor affecting the development and prognosis of the nervous system in premature infants. Early diagnosis and treatment are of great... (Review)
Review
Brain injury is the main factor affecting the development and prognosis of the nervous system in premature infants. Early diagnosis and treatment are of great significance in reducing mortality and disability and improving the prognosis of premature infants. Craniocerebral ultrasound has become an important medical imaging method for evaluating the brain structure of premature infants due to its advantages of being non-invasive, cheap, simple, and bedside dynamic monitoring since it was applied to neonatal clinical practice. This article reviews the application of brain ultrasound to common brain injuries in premature infants.
PubMed: 36860577
DOI: 10.3389/fneur.2023.1095280