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Medicina Sep 2023Premature births are an important health indicator for a country. These children have a higher risk of mortality and morbidity. The main brain injuries in preterm... (Review)
Review
Premature births are an important health indicator for a country. These children have a higher risk of mortality and morbidity. The main brain injuries in preterm infants include white matter injuries, intracranial hemorrhages, and cerebellar injuries. These injuries can be detected through brain ultrasound and magnetic resonance imaging (MRI), with MRI being the most sensitive technique. Perinatal brain injuries may have long-term consequences on the neurodevelopment of preterm infants, with an increased risk of cerebral palsy, cognitive, behavioral, sensory, and learning disorders, among others. It is key to implement prevention strategies and early intervention to reduce the negative consequences of brain injuries associated with prematurity. Key words: prematurity, periventricular leukomalacia, intracranial hemorrhage, neurodevelopmental disorders, cerebral palsy.
Topics: Infant, Newborn; Child; Infant; Female; Pregnancy; Humans; Cerebral Palsy; Infant, Premature; Brain; Brain Injuries; Cerebellum
PubMed: 37714118
DOI: No ID Found -
Neurobiology of Disease Aug 2023Oligodendrocytes (OLs), the myelin-forming cells of the central nervous system, are integral to axonal integrity and function. Hypoxia-ischemia episodes can cause severe... (Review)
Review
Oligodendrocytes (OLs), the myelin-forming cells of the central nervous system, are integral to axonal integrity and function. Hypoxia-ischemia episodes can cause severe damage to these vulnerable cells through excitotoxicity, oxidative stress, inflammation, and mitochondrial dysfunction, leading to axonal dystrophy, neuronal dysfunction, and neurological impairments. OLs damage can result in demyelination and myelination disorders, severely impacting axonal function, structure, metabolism, and survival. Adult-onset stroke, periventricular leukomalacia, and post-stroke cognitive impairment primarily target OLs, making them a critical therapeutic target. Therapeutic strategies targeting OLs, myelin, and their receptors should be given more emphasis to attenuate ischemia injury and establish functional recovery after stroke. This review summarizes recent advances on the function of OLs in ischemic injury, as well as the present and emerging principles that serve as the foundation for protective strategies against OLs deaths.
Topics: Humans; Ischemic Stroke; Oligodendroglia; Myelin Sheath; Central Nervous System; Stroke
PubMed: 37321419
DOI: 10.1016/j.nbd.2023.106200 -
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 -
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 -
The Cochrane Database of Systematic... Oct 2023The Neonatal Task Force of the International Liaison Committee on Resuscitation (ILCOR) makes practice recommendations for the care of newborn infants in the delivery... (Review)
Review
BACKGROUND
The Neonatal Task Force of the International Liaison Committee on Resuscitation (ILCOR) makes practice recommendations for the care of newborn infants in the delivery room (DR). ILCOR recommends that all infants who are gasping, apnoeic, or bradycardic (heart rate < 100 per minute) should be given positive pressure ventilation (PPV) with a manual ventilation device (T-piece, self-inflating bag, or flow-inflating bag) via an interface. The most commonly used interface is a face mask that encircles the infant's nose and mouth. However, gas leak and airway obstruction are common during face mask PPV. Nasal interfaces (single and binasal prongs (long or short), or nasal masks) and laryngeal mask airways (LMAs) may also be used to deliver PPV to newborns in the DR, and may be more effective than face masks.
OBJECTIVES
To determine whether newborn infants receiving PPV in the delivery room with a nasal interface compared to a face mask, laryngeal mask airway (LMA), or another type of nasal interface have reduced mortality and morbidity. To assess whether safety and efficacy of the nasal interface differs according to gestational age or ventilation device.
SEARCH METHODS
Searches were conducted in September 2022 in CENTRAL, MEDLINE, Embase, Epistemonikos, and two trial registries. We searched conference abstracts and checked the reference lists of included trials and related systematic reviews identified through the search.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) and quasi-RCT's that compared the use of nasal interfaces to other interfaces (face masks, LMAs, or one nasal interface to another) to deliver PPV to newborn infants in the DR.
DATA COLLECTION AND ANALYSIS
Each review author independently evaluated the search results against the selection criteria, screened retrieved records, extracted data, and appraised the risk of bias. If they were study authors, they did not participate in the selection, risk of bias assessment, or data extraction related to the study. In such instances, the study was independently assessed by other review authors. We contacted trial investigators to obtain additional information. We completed data analysis according to the standards of Cochrane Neonatal, using risk ratio (RR) and 95% confidence Intervals (CI) to measure the effect of the different interfaces. We used fixed-effect models and the GRADE approach to assess the certainty of the evidence.
MAIN RESULTS
We included five trials, in which 1406 infants participated. They were conducted in 13 neonatal centres across Europe and Australia. Each of these trials compared a nasal interface to a face mask for the delivery of respiratory support to newborn infants in the DR. Potential sources of bias were a lack of blinding to treatment allocation of the caregivers and investigators in all trials. The evidence suggests that resuscitation with a nasal interface in the DR, compared with a face mask, may have little to no effect on reducing death before discharge (typical risk ratio (RR) 0.72, 95% CI 0.47 to 1.13; 3 studies, 1124 infants; low-certainty evidence). Resuscitation with a nasal interface may reduce the rate of intubation in the DR, but the evidence is very uncertain (RR 0.68, 95% CI 0.54 to 0.85; 5 studies, 1406 infants; very low-certainty evidence). The evidence is very uncertain for the rate of intubation within 24 hours of birth (RR 0.97, 95% CI 0.85 to 1.09; 3 studies, 749 infants; very low-certainty evidence), endotracheal intubation outside the DR during hospitalisation (RR 1.15, 95% CI 0.93 to 1.42; 1 study, 144 infants; very low-certainty evidence) and cranial ultrasound abnormalities (intraventricular haemorrhage (IVH) grade ≥ 3, or periventricular leukomalacia; RR 0.94, 95% CI 0.55 to 1.61; 3 studies, 749 infants; very low-certainty evidence). Resuscitation with a nasal interface in the DR, compared with a face mask, may have little to no effect on the incidence of air leaks (RR 1.09, 95% CI 0.85 to 1.09; 2 studies, 507 infants; low-certainty evidence), or the need for supplemental oxygen at 36 weeks' corrected gestational age (RR 1.06, 95% CI 0.8 to 1.40; 2 studies, 507 infants; low-certainty evidence). We identified one ongoing study, which compares a nasal mask to a face mask to deliver PPV to infants in the DR. We did not identify any completed trials that compared nasal interfaces to LMAs or one nasal interface to another.
AUTHORS' CONCLUSIONS
Nasal interfaces were found to offer comparable efficacy to face masks (low- to very low-certainty evidence), supporting resuscitation guidelines that state that nasal interfaces are a comparable alternative to face masks for providing respiratory support in the DR. Resuscitation with a nasal interface may reduce the rate of intubation in the DR when compared with a face mask. However, the evidence is very uncertain. This uncertainty is attributed to the use of a new ventilation system in the nasal interface group in two of the five trials. As such, it is not possible to differentiate separate, specific effects related to the ventilation device or to the interface in these studies.
Topics: Infant, Newborn; Humans; Resuscitation; Positive-Pressure Respiration; Respiration, Artificial; Intermittent Positive-Pressure Ventilation; Intubation, Intratracheal
PubMed: 37787113
DOI: 10.1002/14651858.CD009102.pub2 -
Neuroradiology Feb 2024Preterm children with cerebral palsy (CP) often have varying hand dysfunction, while the specific brain injury with periventricular leukomalacia (PVL) cannot quite...
PURPOSE
Preterm children with cerebral palsy (CP) often have varying hand dysfunction, while the specific brain injury with periventricular leukomalacia (PVL) cannot quite explain its mechanism. We aimed to investigate glymphatic activity using diffusion tensor image analysis along the perivascular space (DTI-ALPS) method and evaluate its association with brain lesion burden and hand dysfunction in children with CP secondary to PVL.
METHODS
We retrospectively enrolled 18 children with bilateral spastic CP due to PVL and 29 age- and sex-matched typically developing controls. The Manual Ability Classification System (MACS) was used to assess severity of hand dysfunction in CP. A mediation model was performed to explore the relationship among the DTI-ALPS index, brain lesion burden, and the MACS level in children with CP.
RESULTS
There were significant differences in the DTI-ALPS index between children with CP and their typically developing peers. The DTI-ALPS index of the children with CP was lower than that of the controls (1.448 vs. 1.625, P = 0.003). The mediation analysis showed that the DTI-ALPS index fully mediated the relationship between brain lesion burden and the MACS level (c' = 0.061, P = 0.665), explaining 80% of the effect.
CONCLUSION
This study provides new insights into the neural basis of hand dysfunction in children with CP, demonstrating an important role of glymphatic impairment in such patients. These results suggest that PVL might affect hand function in children with CP by disrupting glymphatic drainage.
Topics: Child; Infant, Newborn; Humans; Cerebral Palsy; Leukomalacia, Periventricular; Glymphatic System; Retrospective Studies; Hand
PubMed: 38129651
DOI: 10.1007/s00234-023-03269-9 -
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 -
Journal of Neonatal-perinatal Medicine Jun 2024Fetal inflammatory response syndrome (FIRS), the fetal equivalent of chorioamnionitis, is associated with poorer neonatal outcomes. FIRS is diagnosed through placental...
BACKGROUND
Fetal inflammatory response syndrome (FIRS), the fetal equivalent of chorioamnionitis, is associated with poorer neonatal outcomes. FIRS is diagnosed through placental histology, namely by the identification of funisitis (inflammation of the umbilical cord) and chorionic vasculitis (inflammation of fetal vessels within the chorionic plate). The aim of this study was to identify and evaluate associations between FIRS and neonatal outcomes in preterm neonates.
METHODS
We performed a retrospective cohort study at a level III neonatal intensive care unit (NICU), from January 1st 2008 to December 31st 2022, involving all inborn neonates with a gestational age below 30 weeks. We compared preterm neonates based on whether their placental histology described funisitis with chorionic vasculitis (FCV) or not.
RESULTS
The study included 113 preterms, 27 (23.9%) of those had FCV and 86 (76.1%) did not. After adjusting to gestational age, prolonged rupture of membranes and preeclampsia, FCV was independently associated with the development of early-onset sepsis (OR = 7.3, p = 0.021) and cystic periventricular leukomalacia (OR = 4.6, p = 0.004).
CONCLUSION
The authors identified an association between FIRS and the development of early-onset sepsis and cystic periventricular leukomalacia, highlighting the importance of early detection and management of this condition in order to improve long-term neonatal outcomes.
PubMed: 38905060
DOI: 10.3233/NPM-240017 -
Clinical Nutrition (Edinburgh, Scotland) Aug 2023Gut immaturity leads to feeding difficulties in very preterm infants (<32 weeks gestation at birth). Maternal milk (MM) is the optimal diet but often absent or... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND & AIMS
Gut immaturity leads to feeding difficulties in very preterm infants (<32 weeks gestation at birth). Maternal milk (MM) is the optimal diet but often absent or insufficient. We hypothesized that bovine colostrum (BC), rich in protein and bioactive components, improves enteral feeding progression, relative to preterm formula (PF), when supplemented to MM. Aim of the study is to determine whether BC supplementation to MM during the first 14 days of life shortens the time to full enteral feeding (120 mL/kg/d, TFF120).
METHODS
This was a multicenter, randomized, controlled trial at seven hospitals in South China without access to human donor milk and with slow feeding progression. Infants were randomly assigned to receive BC or PF when MM was insufficient. Volume of BC was restricted by recommended protein intake (4-4.5 g/kg/d). Primary outcome was TFF120. Feeding intolerance, growth, morbidities and blood parameters were recorded to assess safety.
RESULTS
A total of 350 infants were recruited. BC supplementation had no effect on TFF120 in intention-to-treat analysis [n (BC) = 171, n (PF) = 179; adjusted hazard ratio, aHR: 0.82 (95% CI: 0.64, 1.06); P = 0.13]. Body growth and morbidities did not differ, but more cases of periventricular leukomalacia were detected in the infants fed BC (5/155 vs. 0/181, P = 0.06). Blood chemistry and hematology data were similar between the intervention groups.
CONCLUSIONS
BC supplementation during the first two weeks of life did not reduce TFF120 and had only marginal effects on clinical variables. Clinical effects of BC supplementation on very preterm infants in the first weeks of life may depend on feeding regimen and remaining milk diet.
TRIAL REGISTRATION
http://www.
CLINICALTRIALS
gov: NCT03085277.
Topics: Infant; Pregnancy; Female; Infant, Newborn; Humans; Animals; Cattle; Infant, Premature; Colostrum; Dietary Supplements; Milk, Human; Infant, Very Low Birth Weight; Infant, Premature, Diseases; Fetal Growth Retardation; Enterocolitis, Necrotizing
PubMed: 37437359
DOI: 10.1016/j.clnu.2023.06.024 -
Pediatric Neurology Nov 2023The development of the central nervous system can be directly disrupted by a variety of acquired factors, including infectious, inflammatory, hypoxic-ischemic, and toxic... (Review)
Review
The development of the central nervous system can be directly disrupted by a variety of acquired factors, including infectious, inflammatory, hypoxic-ischemic, and toxic insults. Influences external to the fetus also impact neurodevelopment, including placental health, maternal comorbidities, adverse experiences, environmental exposures, and social determinants of health. Acquired perinatal brain insults tend to affect the developing brain in a stage-specific manner that reflects the susceptible cell types, developmental processes, and risk factors present at the time of the insult. In this review, we discuss the pathophysiology, neurodevelopmental outcomes, and management of common acquired perinatal brain conditions. In the fetal brain, we divide insults based on trimester, and in the postnatal brain, we focus on common pathologies that have a presentation dependent on gestational age at birth: white matter injury and germinal matrix hemorrhage/intraventricular hemorrhage in preterm infants and hypoxic-ischemic encephalopathy in term infants. Although specific treatments for fetal and newborn brain disorders are currently limited, we emphasize therapies in preclinical or early clinical phases of the development pipeline. The growing number of novel cell type- and stage-specific emerging therapies suggests that in the near future we may have a dramatically improved ability to treat acquired perinatal brain disorders and to mitigate the associated neurodevelopmental consequences.
PubMed: 37625929
DOI: 10.1016/j.pediatrneurol.2023.08.001