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Experimental and Therapeutic Medicine Jul 2021Pregnancy, labor and childbirth are accompanied by excessive oxidative aggression. The excessive formation of free radicals [reactive oxygen species (ROS), reactive... (Review)
Review
Pregnancy, labor and childbirth are accompanied by excessive oxidative aggression. The excessive formation of free radicals [reactive oxygen species (ROS), reactive nitrogen species (RNS), chlorine reactive species (CRS)] causes cellular oxidative damage, which can be scavenged by enzymatic or non-enzymatic antioxidants in normal healthy pregnancy, physiological labor and delivery without any complications. An imbalance between the pro-oxidant and antioxidant factors may lead to oxidative stress, which contributes to the development of many diseases. This oxidative aggression can be a precursor for pathologies in the pregnant woman including eclampsia, miscarriage, preterm labor, and intrauterine growth retardation; in the offspring it may lead to bronchopulmonary dysplasia/chronic lung disease, necrotizing enterocolitis, retinopathy of prematurity, and periventricular leukomalacia. This review summarizes the studies conducted to identify the mechanisms of oxidative stress and the effect of cell membrane oxidation, the mechanisms that are behind oxidative stress-related diseases, and also those studies which have demonstrated the effect of antioxidants in preventing diseases or diminishing the effects of oxidative stress in the body, in obstetrics and neonatology.
PubMed: 34055070
DOI: 10.3892/etm.2021.10203 -
Seminars in Perinatology Apr 2023Preterm birth and intrapartum related complications account for a substantial amount of mortality and morbidity in the neonatal period despite significant advancements... (Review)
Review
Preterm birth and intrapartum related complications account for a substantial amount of mortality and morbidity in the neonatal period despite significant advancements in neonatal-perinatal care. Currently, there is a noticeable lack of curative or preventative therapies available for any of the most common complications of prematurity including bronchopulmonary dysplasia, necrotizing enterocolitis, intraventricular hemorrhage, periventricular leukomalacia and retinopathy of prematurity or hypoxic-ischemic encephalopathy, the main cause of perinatal brain injury in term infants. Mesenchymal stem/stromal cell-derived therapy has been an active area of investigation for the past decade and has demonstrated encouraging results in multiple experimental models of neonatal disease. It is now widely acknowledged that mesenchymal stem/stromal cells exert their therapeutic effects via their secretome, with the principal vector identified as extracellular vesicles. This review will focus on summarizing the current literature and investigations on mesenchymal stem/stromal cell-derived extracellular vesicles as a treatment for neonatal diseases and examine the considerations to their application in the clinical setting.
Topics: Infant; Pregnancy; Female; Infant, Newborn; Humans; Secretome; Premature Birth; Infant, Premature; Infant, Premature, Diseases; Bronchopulmonary Dysplasia; Stem Cells
PubMed: 36990921
DOI: 10.1016/j.semperi.2023.151730 -
Paediatrics & Child Health Jun 2020Routine brain imaging to detect injuries affecting preterm infants is used to predict long-term outcomes and identify complications that might necessitate an... (Review)
Review
Routine brain imaging to detect injuries affecting preterm infants is used to predict long-term outcomes and identify complications that might necessitate an intervention. Although magnetic resonance imaging may be indicated in some specific cases, head ultrasound is the most widely used technique and, because of portability and ease of access, is the best modality for routine imaging. Routine head ultrasound examination is recommended for all infants born at or before 31+6 weeks gestation. For preterm neonates born between 32+0 to 36+6 weeks gestation, routine head ultrasound is recommended only in presence of risk factors for intracranial hemorrhage or ischemia. Brain imaging in the first 7 to 14 days postbirth is advised to detect most germinal matrix and intraventricular hemorrhages. Repeat imaging at 4 to 6 weeks of age is recommended to detect white matter injury.
PubMed: 32549742
DOI: 10.1093/pch/pxaa033 -
Pediatric Physical Therapy : the... Jul 2023To identify the earliest predictors of risk for diagnosis of cerebral palsy (CP). (Review)
Review
PURPOSE
To identify the earliest predictors of risk for diagnosis of cerebral palsy (CP).
METHODS
A comprehensive literature search was conducted using various databases. The publications were reviewed to identify risk factors for CP from conception to early infancy. Studies were critically appraised with Joanna Briggs Institute guidelines for quality appraisal and evaluated for risk of bias using the Agency for Health Care Research and Quality guidelines.
RESULTS
The initial search yielded 129 studies and 20 studies were included. Forty-seven risk factors for CP were extracted of which several were duplicate terms. The significant risk factors found to be indicative of CP were low birth weight (<1500 g), birth at less than 28 weeks of gestational age, periventricular leukomalacia, grade 3 or 4 intraventricular hemorrhage, preeclampsia, prematurity, an Apgar score of less than 4 at the first minute, birth asphyxia, preterm premature rupture of membrane, and absent fidgety movements.
CONCLUSION
Twenty-three factors were consistently reported as predictors of CP.
Topics: Infant, Newborn; Pregnancy; Female; Humans; Cerebral Palsy; Infant, Premature; Gestational Age; Leukomalacia, Periventricular; Infant, Premature, Diseases; Risk Factors
PubMed: 37126801
DOI: 10.1097/PEP.0000000000001020 -
Neonatology 2023Cystic periventricular leukomalacia (PVL) is the most common white matter injury and a common cause of cerebral palsy in preterm infants. Postnatal epilepsy may occur...
INTRODUCTION
Cystic periventricular leukomalacia (PVL) is the most common white matter injury and a common cause of cerebral palsy in preterm infants. Postnatal epilepsy may occur after cystic PVL, but their causal relationship remains uncertain. Our aim was to validate the contribution of cystic PVL to postnatal epilepsy in very preterm infants and demonstrate their seizure characteristics.
METHODS
This prospective cohort study enrolled 1,342 preterm infants (birth weight <1,500 g and gestational age <32 weeks) from 2003 to 2015. Cystic PVL was diagnosed by serial cerebral ultrasound, and other comorbidities were recorded during hospitalization. Neurological developments and consequences, including epilepsy, were serially accessed until the age of 5.
RESULTS
A total of 976 preterm infants completed a 5-year neurological follow-up; 47 (4.8%) had cystic PVL. Preterm infants with cystic PVL were commonly associated with other comorbidities, including necrotizing enterocolitis stage III, neonatal seizures, and intraventricular hemorrhage during hospitalization. At age 5, 14 of the 47 (29.8%) preterm infants with cystic PVL had postnatal epilepsy. After adjusting for gender, gestational age, and three common comorbidities, cystic PVL was an independent risk factor for postnatal epilepsy (adjust OR: 16.2; 95% CI: 6.8-38.4; p < 0.001). Postnatal epilepsy after cystic PVL was commonly the generalized type (13 of 14, 92.9%), not intractable and most occurred after 1 year of age.
DISCUSSION/CONCLUSION
Cystic PVL would independently lead to postnatal epilepsy. Preterm infants with cystic PVL are at risk of postnatal epilepsy after age 1 in addition to cerebral palsy.
Topics: Infant; Female; Infant, Newborn; Humans; Leukomalacia, Periventricular; Infant, Premature; Cerebral Palsy; Prospective Studies; Infant, Premature, Diseases; Fetal Growth Retardation; Epilepsy; Seizures; Infant, Very Low Birth Weight
PubMed: 37071988
DOI: 10.1159/000529998 -
European Journal of Paediatric... May 2021To describe the frequency, motor phenotype, clinical patterns and functional consequences of dystonia in patients with cerebral palsy (CP) in the setting of...
OBJECTIVE
To describe the frequency, motor phenotype, clinical patterns and functional consequences of dystonia in patients with cerebral palsy (CP) in the setting of periventricular leukomalacia.
METHODS
Retrospective analysis of a cohort of 31 patients with CP and periventricular leukomalacia. Gross Motor Function Classification System (GMFCS) and Manual Ability Classification System (MACS) were used to classify functional ability. Spasticity was rated using the Modified Ashworth Scale. Presence of dystonia was assessed by reviewing video recordings, and its severity by using the Burke-Fahn-Marsden Dystonia Rating Scale.
RESULTS
All patients showed evidence of dystonia involving upper and/or lower limbs, neck, trunk, mouth and eyes in order of frequency. In 29% of patients dystonia involved only the limbs and in 71% it was multifocal. Dystonia severity ranged from slight to severe. Severity and distribution of dystonia did not correlate with gender, age, weeks of gestation or duration of neonatal unit stay. GMFCS and MACS correlated with dystonia but not with spasticity.
CONCLUSIONS
Severity of dystonia, but not spasticity is associated with the severity of motor functional disability in CP patients with periventricular leukomalacia and demonstrates the key role of dystonia in the motor function of these patients.
Topics: Activities of Daily Living; Cerebral Palsy; Child; Child, Preschool; Cohort Studies; Dystonia; Humans; Leukomalacia, Periventricular; Male; Motor Skills; Retrospective Studies; Severity of Illness Index
PubMed: 33743389
DOI: 10.1016/j.ejpn.2021.03.005 -
Journal of Neuroinflammation Jun 2023Germinal matrix hemorrhage is a devastating disease of pre-term infancy commonly resulting in post-hemorrhagic hydrocephalus, periventricular leukomalacia, and...
BACKGROUND
Germinal matrix hemorrhage is a devastating disease of pre-term infancy commonly resulting in post-hemorrhagic hydrocephalus, periventricular leukomalacia, and subsequent neurocognitive deficits. We demonstrate vascular expression of the adhesion molecule P-selectin after GMH and investigate a strategy to specifically target complement inhibition to sites of P-selectin expression to mitigate the pathological sequelae of GMH.
METHODS
We prepared two fusion proteins consisting of different anti-P-selectin single chain antibodies (scFv's) linked to the complement inhibitor Crry. One scFv targeting vehicle (2.12scFv) blocked the binding of P-selectin to its PSGL-1 ligand expressed on leukocytes, whereas the other targeting vehicle (2.3scFv) bound P-selectin without blocking ligand binding. Post-natal C57BL/6 J mice on day 4 (P4) were subjected to collagenase induced-intraventricular hemorrhage and treated with 2.3Psel-Crry, 2.12Psel-Crry, or vehicle.
RESULTS
Compared to vehicle treatment, 2.3Psel-Crry treatment after induction of GMH resulted in reduced lesion size and mortality, reduced hydrocephalus development, and improved neurological deficit measurements in adolescence. In contrast, 2.12Psel-Crry treatment resulted in worse outcomes compared to vehicle. Improved outcomes with 2.3Psel-Crry were accompanied by decreased P-selectin expression, and decreased complement activation and microgliosis. Microglia from 2.3Psel-Crry treated mice displayed a ramified morphology, similar to naïve mice, whereas microglia in vehicle treated animals displayed a more ameboid morphology that is associated with a more activated status. Consistent with these morphological characteristics, there was increased microglial internalization of complement deposits in vehicle compared to 2.3Psel-Crry treated animals, reminiscent of aberrant C3-dependent microglial phagocytosis that occurs in other (adult) types of brain injury. In addition, following systemic injection, 2.3Psel-Crry specifically targeted to the post-GMH brain. Likely accounting for the unexpected finding that 2.12Psel-Crry worsens outcome following GMH was the finding that this construct interfered with coagulation in this hemorrhagic condition, and specifically with heterotypic platelet-leukocyte aggregation, which express P-selectin and PSGL-1, respectively.
CONCLUSIONS
GMH induces expression of P-selectin, the targeting of which with a complement inhibitor protects against pathogenic sequelae of GMH. A dual functioning construct with both P-selectin and complement blocking activity interferes with coagulation and worsens outcomes following GMH, but has potential for treatment of conditions that incorporate pathological thrombotic events, such as ischemic stroke.
Topics: Animals; Mice; Cerebral Hemorrhage; Complement Inactivating Agents; Complement System Proteins; Hydrocephalus; Ligands; Mice, Inbred C57BL; P-Selectin
PubMed: 37322469
DOI: 10.1186/s12974-023-02828-4 -
The Israel Medical Association Journal... Oct 2021Cystic periventricular leukomalacia (cPVL) is a strong indicator of subsequent motor and developmental impairments in premature infants. There is a paucity of...
BACKGROUND
Cystic periventricular leukomalacia (cPVL) is a strong indicator of subsequent motor and developmental impairments in premature infants. There is a paucity of publications on biomarkers of cPVL.
OBJECTIVES
To determine C-reactive protein (CRP) levels during the first week of life of preterm infants who later developed cPVL and to identify the association between CRP levels with perinatal factors.
METHODS
We retrospectively included infants ≤ 32 weeks gestation and/or birth weights ≤ 1500 grams; 17 with a cranial ultrasound diagnosis of cPVL and 54 with normal ultrasounds. Serum CRP levels were measured during days 1-7 (CRP1-7d) of life and subdivided into two timing groups: days 1-3 (CRP1-3d) and days 4-7 (CRP4-7d).
RESULTS
The cPVL group had significantly higher mean CRP4-7d levels compared to controls (12.75 ± 21.2 vs. 2.23 ± 3.1, respectively, P = 0.03), while CRP1-3d levels were similar. CRP1-7d levels were significantly correlated with maximal fraction of inspired oxygen during the first 12 hours of life (FiO2-12h, r = 0.51, P < 0.001]. Additional risk factors were not associated with CRP levels.
CONCLUSIONS
Our finding of elevated CRP4-7d levels and later development of cPVL supports earlier studies on the involvement of inflammation in the pathogenesis of cPVL. Whether CRP could serve as a biomarker of cPVL and its correlation with outcomes, awaits further trials. Furthermore, the correlation between FiO2-12h and CRP1-7d levels suggest that hypoxia and/or hyperoxia may serve as a trigger in the activation of inflammation during the first days of life of preterm infants.
Topics: Biomarkers; Brain; C-Reactive Protein; Early Diagnosis; Female; Gestational Age; Humans; Infant, Newborn; Infant, Premature; Inflammation; Leukomalacia, Periventricular; Male; Oxygen Consumption; Risk Assessment; Risk Factors; Ultrasonography
PubMed: 34672442
DOI: No ID Found -
The Journal of Pediatrics Nov 2023To survey the incidence of intraventricular hemorrhage (IVH) and periventricular leukomalacia (PVL) by gestational age and to report the impact on mortality and...
The Impact of Intraventricular Hemorrhage and Periventricular Leukomalacia on Mortality and Neurodevelopmental Outcome in Very Preterm and Very Low Birthweight Infants: A Prospective Population-based Cohort Study.
OBJECTIVE
To survey the incidence of intraventricular hemorrhage (IVH) and periventricular leukomalacia (PVL) by gestational age and to report the impact on mortality and neurodevelopmental outcome in very preterm/very low birthweight infants.
STUDY DESIGN
This was a population-based cohort study of 1927 very preterm/very low birthweight infants born in 2014-2016 and admitted to Flemish neonatal intensive care units. Infants underwent standard follow-up assessment until 2 years corrected age with the Bayley Scales of Infant and Toddler Development and neurological assessments.
RESULTS
No brain lesion was present in 31% of infants born at <26 weeks of gestation and 75.8% in infants born at 29-32 weeks of gestation. The prevalence of low-grade IVH/PVL (grades I and II) was 16.8% and 12.7%, respectively. Low-grade IVH/PVL was not related significantly to an increased likelihood of mortality, motor delay, or cognitive delay, except for PVL grade II, which was associated with a 4-fold increase in developing cerebral palsy (OR, 4.1; 95% CI, 1.2-14.6). High-grade lesions (III-IV) were present in 22.0% of the infants born at <26 weeks of gestational and 3.1% at 29-32 weeks of gestation, and the odds of death were ≥14.0 (IVH: OR, 14.0; 95% CI, 9.0-21.9; PVL: OR, 14.1; 95% CI, 6.6-29.9). PVL grades III-IV showed an increased odds of 17.2 for motor delay and 12.3 for cerebral palsy, but were not found to be associated significantly with cognitive delay (OR, 2.9; 95% CI, 0.5-17.5; P = .24).
CONCLUSIONS
Both the prevalence and severity of IVH/PVL decreased significantly with advancing gestational age. More than 75% of all infants with low grades of IVH/PVL showed normal motor and cognitive outcome at 2 years corrected age. High-grade PVL/IVH has become less common and is associated with adverse outcomes.
Topics: Infant, Newborn; Infant; Humans; Child; Leukomalacia, Periventricular; Infant, Extremely Premature; Cerebral Palsy; Cohort Studies; Prospective Studies; Infant, Very Low Birth Weight; Cerebral Hemorrhage; Infant, Premature, Diseases
PubMed: 37402440
DOI: 10.1016/j.jpeds.2023.113600 -
Developmental Medicine and Child... Jan 2023To determine the prevalence of dystonia in individuals with periventricular leukomalacia (PVL) and spastic cerebral palsy (CP), but without basal ganglia and thalamic...
AIM
To determine the prevalence of dystonia in individuals with periventricular leukomalacia (PVL) and spastic cerebral palsy (CP), but without basal ganglia and thalamic injury (BGTI) on brain magnetic resonance imaging (MRI).
METHOD
This was a retrospective study of individuals with spastic CP and PVL on MRI evaluated between 2005 and 2018 in a CP center. Individuals with non-PVL brain lesions on MRI, including BGTI, were excluded. Dystonia was assessed via blinded review of neurological exam videos by pediatric movement disorders specialists.
RESULTS
Eighty-five participants (45 males, 40 females; mean age at videotaping 12 years [standard deviation 5 years 6 months], range 4-26 years) met inclusion and exclusion criteria. Of these participants, 50 (59%) displayed dystonia in their exam videos. The most common locations of dystonia were the fingers and hip adductors. The prevalence of dystonia was unaffected by the gestational age or severity of PVL, and was affected by Gross Motor Function Classification System level.
INTERPRETATION
Dystonia is common in individuals with spastic CP and PVL, even without BGTI on MRI. Our findings suggest vigilance for dystonia in individuals with spastic CP should remain high, even without MRI evidence of BGTI.
WHAT THIS PAPER ADDS
Individuals with spastic cerebral palsy and isolated periventricular leukomalacia on magnetic resonance imaging commonly display dystonia. Common sites of dystonia are in the fingers and hip adductors.
Topics: Infant, Newborn; Male; Female; Child; Humans; Infant; Child, Preschool; Leukomalacia, Periventricular; Cerebral Palsy; Muscle Spasticity; Dystonia; Retrospective Studies; Magnetic Resonance Imaging; Dystonic Disorders
PubMed: 35661146
DOI: 10.1111/dmcn.15300