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Research in Developmental Disabilities Apr 2023Thanks to Magnetic Resonance Imaging (MRI) it is now possible to diagnose lesions of the central nervous system (CNS) such as periventricular leukomalacia (PVL) from the... (Review)
Review
BACKGROUND
Thanks to Magnetic Resonance Imaging (MRI) it is now possible to diagnose lesions of the central nervous system (CNS) such as periventricular leukomalacia (PVL) from the first days of life. However, there are still few studies aimed at describing the relationship between MRI and the outcome of visual function in patients with PVL.
AIM
To systematically review and investigate the relationship between MRI neuroimaging and visual impairment arising from PVL.
METHODS AND PROCEDURES
Three electronic databases (PubMed, SCOPUS, Web of Science) were consulted from 15 June 2021-30 September 2021. Of the 81 records identified, 10 were selected for the systematic review. The STROBE Checklist was used to assess the quality of the observational studies.
OUTCOME AND RESULTS
PVL on MRI was found to have a strong association with visual impairment in the various aspects of visual function (visual acuity, ocular motility, visual field); in 60% of these articles, the selected subjects also reported damage to optical radiations.
CONCLUSION AND IMPLICATIONS
there is a clear need for more extensive and detailed studies on the correlation between PVL and visual impairment, in order to set up a personalized early therapeutic-rehabilitation plan. WHAT THIS PAPER ADDS?: Over the past decades numerous studies have reported increasing evidence that one of the most frequent sequelae in subjects with PVL, in addition to motor impairment, is the impairment of visual function even if it is still not clear what different authors mean with the term visual impairment. This systematic review presents an overview of the relationship between structural correlates of MRI and visual impairment in children with periventricular leukomalacia. Interesting correlations emerge between MRI radiological finding and consequences on visual function especially between damage to the periventricular white matter and the impairment of various aspects of visual function and also between the impairment of optical radiation and visual acuity. Thanks to this literature revision, it is now clear that MRI plays an important role in the screening and diagnosis of significant intracranial brain changes in very young children in particular about the outcome of visual function. This is of great relevance since that visual function represents one of the main adaptive functions in the development of the child.
Topics: Infant, Newborn; Humans; Child; Child, Preschool; Leukomalacia, Periventricular; Brain; Magnetic Resonance Imaging; Vision, Low
PubMed: 36796269
DOI: 10.1016/j.ridd.2023.104439 -
The Cochrane Database of Systematic... Oct 2017Damage caused by lung overdistension (volutrauma) has been implicated in the development of bronchopulmonary dysplasia (BPD). Modern neonatal ventilation modes can... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Damage caused by lung overdistension (volutrauma) has been implicated in the development of bronchopulmonary dysplasia (BPD). Modern neonatal ventilation modes can target a set tidal volume as an alternative to traditional pressure-limited ventilation (PLV) using a fixed inflation pressure. Volume-targeted ventilation (VTV) aims to produce a more stable tidal volume in order to reduce lung damage and stabilise the partial pressure of carbon dioxide (pCO).
OBJECTIVES
To determine whether VTV compared with PLV leads to reduced rates of death and death or BPD in newborn infants and to determine whether use of VTV affected outcomes including air leak, cranial ultrasound findings and neurodevelopment.
SEARCH METHODS
We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 12), MEDLINE via PubMed (1966 to 13 January 2017), Embase (1980 to 13 January 2017) and CINAHL (1982 to 13 January 2017). We also searched clinical trials databases, conference proceedings and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. We contacted the principal investigators of studies to obtain supplementary information.
SELECTION CRITERIA
Randomised and quasi-randomised trials comparing VTV versus PLV in infants of less than 44 weeks' postmenstrual age and reporting clinically relevant outcomes.
DATA COLLECTION AND ANALYSIS
We assessed risk of bias for each trial using Cochrane methodology. We evaluated quality of evidence for each outcome using GRADE criteria. We tabulated mortality, rates of BPD, short-term clinical outcomes and long-term developmental outcomes.
STATISTICS
for categorical outcomes, we calculated typical estimates for risk ratios (RR), risk differences (RD) and number needed to treat for an additional beneficial outcome (NNTB). For continuous variables, we calculated typical estimates for mean differences (MD). We used 95% confidence intervals (CI) and assumed a fixed-effect model for meta-analysis.
MAIN RESULTS
Twenty randomised trials met our inclusion criteria; 16 parallel trials (977 infants) and four cross-over trials (88 infants). No studies were blinded and the quality of evidence for outcomes assessed varied from moderate to low.We found no difference in the primary outcome, death before hospital discharge, between VTV modes versus PLV modes (typical RR 0.75, 95% CI 0.53 to 1.07; low quality evidence). However, there was moderate quality evidence that the use of VTV modes resulted in a reduction in the primary outcome, death or BPD at 36 weeks' gestation (typical RR 0.73, 95% CI 0.59 to 0.89; typical NNTB 8, 95% CI 5 to 20) and the following secondary outcomes: rates of pneumothorax (typical RR 0.52, 95% CI 0.31 to 0.87; typical NNTB 20, 95% CI 11 to 100), mean days of mechanical ventilation (MD -1.35 days, 95% CI -1.83 to -0.86), rates of hypocarbia (typical RR 0.49, 95% CI 0.33 to 0.72; typical NNTB 3, 95% CI 2 to 5), rates of grade 3 or 4 intraventricular haemorrhage (typical RR 0.53, 95% CI 0.37 to 0.77; typical NNTB 11, 95% CI 7 to 25) and the combined outcome of periventricular leukomalacia with or without grade 3 or 4 intraventricular haemorrhage (typical RR 0.47, 95% CI 0.27 to 0.80; typical NNTB 11, 95% CI 7 to 33). VTV modes were not associated with any increased adverse outcomes.
AUTHORS' CONCLUSIONS
Infants ventilated using VTV modes had reduced rates of death or BPD, pneumothoraces, hypocarbia, severe cranial ultrasound pathologies and duration of ventilation compared with infants ventilated using PLV modes. Further studies are needed to identify whether VTV modes improve neurodevelopmental outcomes and to compare and refine VTV strategies.
Topics: Bronchopulmonary Dysplasia; Humans; Infant, Newborn; Infant, Premature; Intermittent Positive-Pressure Ventilation; Pressure; Randomized Controlled Trials as Topic; Tidal Volume
PubMed: 29039883
DOI: 10.1002/14651858.CD003666.pub4 -
Revista de Neurologia Jul 2017There is a huge disparity in the description of the prevalence and risk factors of periventricular leukomalacia in preterm infants. (Review)
Review
INTRODUCTION
There is a huge disparity in the description of the prevalence and risk factors of periventricular leukomalacia in preterm infants.
AIMS
To describe and compare, through a systematic review of the literature, the prevalence of periventricular leukomalacia in preterm infants, as well as to determine the main risk factors associated with its presentation.
SUBJECTS AND METHODS
A systematic review was conducted consulting multiple databases of the last 20 years. The search terms were: periventricular leukomalacia, prevalence, risk factors and premature birth. We included all studies that mention or led to the prevalence of periventricular leukomalacia and those that referred to its risk factors.
RESULTS
Of the 209 studies identified, we selected 107 studies in which the prevalence of periventricular leukomalacia was mentioned or the risk factors were described. A stratified analysis was performed for the diagnostic technique and gestational age, in addition to a narrative synthesis. Ultrasound detected a prevalence of 14.7% and magnetic resonance of 32.8%. Prevalence in children under 28 weeks was 39.6%; 27.4% in children under 32 weeks and 7.3% in children under 37 weeks. Risk factors include gestational age, intrauterine infection, premature rupture of membranes and chorioamnionitis.
CONCLUSIONS
The prevalence of periventricular leukomalacia in preterm infants is heterogeneous, increases according to the degree of prematurity and is better detected by magnetic resonance. There are multiple factors related to its presentation, the main factor is gestational age.
Topics: Chorioamnionitis; Comorbidity; Female; Fetal Membranes, Premature Rupture; Gestational Age; Humans; Hyperbilirubinemia, Neonatal; Infant, Premature; Infant, Premature, Diseases; Leukomalacia, Periventricular; Magnetic Resonance Imaging; Meconium Aspiration Syndrome; Obesity; Pregnancy; Pregnancy Complications; Pregnancy Complications, Infectious; Prevalence; Risk Factors; Ultrasonography, Prenatal
PubMed: 28675256
DOI: No ID Found -
The Cochrane Database of Systematic... Nov 2015Infants born preterm are at increased risk of developing cognitive and motor impairment compared with infants born at term. Early developmental interventions have been... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Infants born preterm are at increased risk of developing cognitive and motor impairment compared with infants born at term. Early developmental interventions have been provided in the clinical setting with the aim of improving overall functional outcomes for these infants. Long-term benefits of these programmes remain unclear.
OBJECTIVES
Primary objective To compare the effectiveness of early developmental intervention programmes provided post hospital discharge to prevent motor or cognitive impairment in preterm (< 37 weeks) infants versus standard medical follow-up of preterm infants at infancy (zero to < three years), preschool age (three to < five years), school age (five to < 18 years) and adulthood (≥ 18 years). Secondary objectives To perform subgroup analyses to determine the following.• Effects of gestational age, birth weight and brain injury (periventricular leukomalacia (PVL)/intraventricular haemorrhage (IVH)) on cognitive and motor outcomes when early intervention is compared with standard follow-up. ∘ Gestational age: < 28 weeks, 28 to < 32 weeks, 32 to < 37 weeks. ∘ Birth weight: < 1000 grams, 1000 to < 1500 grams, 1500 to < 2500 grams. ∘ Brain injury: absence or presence of grade III or grade IV IVH or cystic PVL (or both) or an abnormal ultrasound/magnetic resonance image (MRI) before initiation of the intervention.• Effects of interventions started during inpatient stay with a post-discharge component versus standard follow-up care.• Effects of interventions focused on the parent-infant relationship, infant development or both compared with standard follow-up care.To perform sensitivity analysis to identify the following.• Effects on motor and cognitive impairment when early developmental interventions are provided within high-quality randomised trials with low risk of bias for sequence generation, allocation concealment, blinding of outcome measures and selective reporting bias.
SEARCH METHODS
The search strategy of the Cochrane Neonatal Review Group was used to identify randomised and quasi-randomised controlled trials of early developmental interventions provided post hospital discharge. Two review authors independently searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE Advanced, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO and EMBASE (1966 to August 2015).
SELECTION CRITERIA
Studies included had to be randomised or quasi-randomised controlled trials of early developmental intervention programmes that began within the first 12 months of life for infants born before 37 weeks' gestational age. Interventions could commence on an inpatient basis but had to include a post-discharge component for inclusion in this review. Outcome measures were not prespecified, other than that they had to assess cognitive outcomes, motor outcomes or both. Rates of cerebral palsy were documented.
DATA COLLECTION AND ANALYSIS
Two independent review authors extracted and entered data. Cognitive and motor outcomes were pooled by four age groups: infancy (zero to < three years), preschool age (three to < five years), school age (five to < 18 years) and adulthood (≥ 18 years). Meta-analysis using RevMan 5.1 was carried out to determine the effects of early developmental interventions at each age range. Subgroup analyses focused on gestational age, birth weight, brain injury, commencement of the intervention, focus of the intervention and study quality.
MAIN RESULTS
Twenty-five studies met the inclusion criteria (3615 randomly assigned participants). Only 12 of these studies were randomised controlled trials with appropriate allocation concealment. Variability was evident with regard to focus and intensity of the intervention, participant characteristics and length of follow-up. Meta-analysis led to the conclusion that intervention improved cognitive outcomes at infancy (developmental quotient (DQ): standardised mean difference (SMD) 0.32 standard deviations (SDs), 95% confidence interval (CI) 0.16 to 0.47; P value < 0.001; 16 studies; 2372 participants) and at preschool age (intelligence quotient (IQ); SMD 0.43 SDs, 95% CI 0.32 to 0.54; P value < 0.001; eight studies; 1436 participants). However, this effect was not sustained at school age (IQ: SMD 0.18 SDs, 95% CI -0.08 to 0.43; P value = 0.17; five studies; 1372 participants). Heterogeneity between studies for cognitive outcomes at infancy and at school age was significant. With regards to motor outcomes, meta-analysis of 12 studies showed a significant effect in favour of early developmental interventions at infancy only; however, this effect was small (motor scale DQ: SMD 0.10 SDs, 95% CI 0.01 to 0.19; P value = 0.03; 12 studies; 1895 participants). No effect was noted on the rate of cerebral palsy among survivors (risk ratio (RR) 0.82, 95% CI 0.52 to 1.27; seven studies; 985 participants). Little evidence showed a positive effect on motor outcomes in the long term, but only five included studies reported outcomes at preschool age (n = 3) or at school age (n = 2).
AUTHORS' CONCLUSIONS
Early intervention programmes for preterm infants have a positive influence on cognitive and motor outcomes during infancy, with cognitive benefits persisting into preschool age. A great deal of heterogeneity between studies was due to the variety of early developmental intervention programmes tested and to gestational ages of included preterm infants; thus, comparisons of intervention programmes were limited. Further research is needed to determine which early developmental interventions are most effective in improving cognitive and motor outcomes, and to discern the longer-term effects of these programmes.
Topics: Birth Weight; Cerebral Palsy; Cognition Disorders; Early Intervention, Educational; Gestational Age; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Motor Skills Disorders; Movement Disorders; Patient Discharge; Psychomotor Disorders; Randomized Controlled Trials as Topic
PubMed: 26597166
DOI: 10.1002/14651858.CD005495.pub4 -
JAMA Network Open Apr 2023Interventions to reduce severe brain injury risk are the prime focus in neonatal clinical trials. (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Interventions to reduce severe brain injury risk are the prime focus in neonatal clinical trials.
OBJECTIVE
To evaluate multiple perinatal interventions across clinical settings for reducing the risk of severe intraventricular hemorrhage (sIVH) and cystic periventricular leukomalacia (cPVL) in preterm neonates.
DATA SOURCES
MEDLINE, Embase, CENTRAL (Cochrane Central Register of Controlled Trials), and CINAHL (Cumulative Index to Nursing and Allied Health Literature) databases were searched from inception until September 8, 2022, using prespecified search terms and no language restrictions.
STUDY SELECTION
Randomized clinical trials (RCTs) that evaluated perinatal interventions, chosen a priori, and reported 1 or more outcomes (sIVH, cPVL, and severe brain injury) were included.
DATA EXTRACTION AND SYNTHESIS
Two co-authors independently extracted the data, assessed the quality of the trials, and evaluated the certainty of the evidence using the Cochrane GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach. Fixed-effects pairwise meta-analysis was used for data synthesis.
MAIN OUTCOMES AND MEASURES
The 3 prespecified outcomes were sIVH, cPVL, and severe brain injury.
RESULTS
A total of 221 RCTs that assessed 44 perinatal interventions (6 antenatal, 6 delivery room, and 32 neonatal) were included. Meta-analysis showed with moderate certainty that antenatal corticosteroids were associated with small reduction in sIVH risk (risk ratio [RR], 0.54 [95% CI, 0.35-0.82]; absolute risk difference [ARD], -1% [95% CI, -2% to 0%]; number needed to treat [NNT], 80 [95% CI, 48-232]), whereas indomethacin prophylaxis was associated with moderate reduction in sIVH risk (RR, 0.64 [95% CI, 0.52-0.79]; ARD, -5% [95% CI, -8% to -3%]; NNT, 20 [95% CI, 13-39]). Similarly, the meta-analysis showed with low certainty that volume-targeted ventilation was associated with large reduction in risk of sIVH (RR, 0.51 [95% CI, 0.36-0.72]; ARD, -9% [95% CI, -13% to -5%]; NNT, 11 [95% CI, 7-23]). Additionally, early erythropoiesis-stimulating agents (RR, 0.68 [95% CI, 0.57-0.83]; ARD, -3% [95% CI, -4% to -1%]; NNT, 34 [95% CI, 22-67]) and prophylactic ethamsylate (RR, 0.68 [95% CI, 0.48-0.97]; ARD, -4% [95% CI, -7% to 0%]; NNT, 26 [95% CI, 13-372]) were associated with moderate reduction in sIVH risk (low certainty). The meta-analysis also showed with low certainty that compared with delayed cord clamping, umbilical cord milking was associated with a moderate increase in sIVH risk (RR, 1.82 [95% CI, 1.03-3.21]; ARD, 3% [95% CI, 0%-6%]; NNT, -30 [95% CI, -368 to -16]).
CONCLUSIONS AND RELEVANCE
Results of this study suggest that a few interventions, including antenatal corticosteroids and indomethacin prophylaxis, were associated with reduction in sIVH risk (moderate certainty), and volume-targeted ventilation, early erythropoiesis-stimulating agents, and prophylactic ethamsylate were associated with reduction in sIVH risk (low certainty) in preterm neonates. However, clinicians should carefully consider all of the critical factors that may affect applicability in these interventions, including certainty of the evidence, before applying them to clinical practice.
Topics: Infant, Newborn; Pregnancy; Female; Humans; Ethamsylate; Parturition; Adrenal Cortex Hormones; Cerebral Hemorrhage; Indomethacin; Brain Injuries
PubMed: 37052920
DOI: 10.1001/jamanetworkopen.2023.7473 -
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 -
American Journal of Obstetrics and... Apr 2015The purpose of this study was to provide an updated summary of the literature regarding the effects of tocolysis with indomethacin on neonatal outcome by systematically... (Meta-Analysis)
Meta-Analysis Review
Antenatal exposure to indomethacin increases the risk of severe intraventricular hemorrhage, necrotizing enterocolitis, and periventricular leukomalacia: a systematic review with metaanalysis.
OBJECTIVE
The purpose of this study was to provide an updated summary of the literature regarding the effects of tocolysis with indomethacin on neonatal outcome by systematically reviewing previously and recently reported data.
STUDY DESIGN
All previously reported studies pertaining to indomethacin tocolysis and neonatal outcomes along with recently reported data were identified with the use of electronic databases that had been supplemented with references that were cited in original studies and review articles. Observational studies that compared neonatal outcomes among preterm infants who were exposed and not exposed to indomethacin were included in this systematic review. Data were extracted and quantitative analyses were performed on those studies that assessed the neonatal outcomes of patients that received antenatal tocolysis with indomethacin.
RESULTS
Twenty-seven observational studies that met criteria for systematic review and metaanalysis were identified. These studies included 8454 infants, of whom 1731 were exposed to antenatal indomethacin and 6723 were not exposed. Relative risks with 95% confidence intervals were calculated for dichotomous outcomes with the use of random and fixed-effects models. Metaanalysis revealed no statistically significant differences in the rates of respiratory distress syndrome, patent ductus arteriosus, neonatal mortality rate, neonatal sepsis, bronchopulmonary dysplasia, or intraventricular hemorrhage (all grades). However, antenatal exposure to indomethacin was associated with an increased risk of severe intraventricular hemorrhage (grade III-IV based on Papile's criteria; relative risk, 1.29; 95% confidence interval, 1.06-1.56), necrotizing enterocolitis (relative risk, 1.36; 95% confidence interval, 1.08-1.71), and periventricular leukomalacia (relative risk, 1.59; 95% confidence interval, 1.17-2.17).
CONCLUSION
The use of indomethacin as a tocolytic agent for preterm labor is associated with an increased risk for severe intraventricular hemorrhage, necrotizing enterocolitis, and periventricular leukomalacia.
Topics: Cerebral Ventricles; Enterocolitis, Necrotizing; Female; Humans; Indomethacin; Infant, Newborn; Infant, Premature; Intracranial Hemorrhages; Leukomalacia, Periventricular; Models, Statistical; Pregnancy; Prenatal Exposure Delayed Effects; Tocolytic Agents
PubMed: 25448524
DOI: 10.1016/j.ajog.2014.10.1091 -
Pediatric Neurology Nov 2021We analyzed the certainty of evidence (CoE) for risk factors of periventricular leukomalacia (PVL) in preterm neonates, a common morbidity of prematurity. (Meta-Analysis)
Meta-Analysis
BACKGROUND
We analyzed the certainty of evidence (CoE) for risk factors of periventricular leukomalacia (PVL) in preterm neonates, a common morbidity of prematurity.
METHODS
Medline, CENTRAL, Embase, and CINAHL were searched. Cohort and case-control studies and randomised randomized controlled trials were included. Data extraction was performed in duplicate. A random random-effects meta-analysis was utilizedused. CoE was evaluated as per Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines.
RESULTS
One hundred eighty-six studies evaluating 95 risk factors for PVL were included. Of the 2,509,507 neonates assessed, 16,569 were diagnosed with PVL. Intraventricular hemorrhage [adjusted odds ratio: 3.22 (2.52-4.12)] had moderate CoE for its association with PVL. Other factors such as hypocarbia, chorioamnionitis, PPROM >48 hour, multifetal pregnancy reduction, antenatal indomethacin, lack of antenatal steroids, perinatal asphyxia, ventilation, shock/hypotension, patent ductus arteriosus requiring surgical ligation, late-onset circulatory collapse, sepsis, necrotizing enterocolitis, and neonatal surgery showed significant association with PVL after adjustment for confounders (CoE: very low to low). Amongst the risk factors associated with mother placental fetal (MPF) triad, there was paucity of literature related to genetic predisposition and defective placentation. Sensitivity analysis revealed that the strength of association between invasive ventilation and PVL decreased over time (P < 0.01), suggesting progress in ventilation strategies. Limited studies had evaluated diffuse PVL.
CONCLUSION
Despite decades of research, our findings indicate that the CoE is low to very low for most of the commonly attributed risk factors of PVL. Future studies should evaluate genetic predisposition and defective placentation in the MPF triad contributing to PVL. Studies evaluating exclusively diffuse PVL are warranted.
Topics: Humans; Infant, Newborn; Infant, Premature, Diseases; Leukomalacia, Periventricular; Risk Factors
PubMed: 34537463
DOI: 10.1016/j.pediatrneurol.2021.08.003 -
PloS One 2019Whether all degrees of periventricular leukomalacia (PVL) and peri-intraventricular haemorrhage (PIVH) have a negative impact on neurodevelopment. (Meta-Analysis)
Meta-Analysis
CONTEXT
Whether all degrees of periventricular leukomalacia (PVL) and peri-intraventricular haemorrhage (PIVH) have a negative impact on neurodevelopment.
OBJECTIVE
To determine the impact of PVL and PIVH in the incidence of cerebral palsy, sensorineural impairment and development scores in preterm neonates. Registered in PROSPERO (CRD42017073113).
DATA SOURCES
PubMed, Embase, SciELO, LILACS, and Cochrane databases.
STUDY SELECTION
Prospective cohort studies evaluating neurodevelopment in children born preterm which performed brain imaging in the neonatal period.
DATA EXTRACTION
Two independent researchers extracted data using a predesigned data extraction sheet.
STATISTICAL METHODS
A random-effects model was used, with Mantel-Haenszel approach and a Sidik-Jonkman method for the estimation of variances, combined with Hartung-Knapp-Sidik-Jonkman correction. Heterogeneity was assessed through the I2 statistic and sensitivity analysis were performed when possible. No funnel plots were generated but publication bias was discussed as a possible limitation.
RESULTS
Our analysis concluded premature children with any degree of PIVH are at increased risk for cerebral palsy (CP) when compared to children with no PIVH (3.4, 95% CI 1.60-7.22; 9 studies), a finding that persisted on subgroup analysis for studies with mean birth weight of less than 1000 grams. Similarly, PVL was associated with CP, both in its cystic (19.12, 95% CI 4.57-79.90; 2 studies) and non-cystic form (9.27, 95% CI 5.93-14.50; 2 studies). We also found children with cystic PVL may be at risk for visual and hearing impairment compared to normal children, but evidence is weak.
LIMITATIONS
Major limitations were the lack of data for PVL in general, especially for the outcome of neurodevelopment, the high heterogeneity among methods used to assess neurodevelopment and the small number of studies, which led to meta-analysis with high heterogeneity and wide confidence intervals.
CONCLUSIONS
There was no evidence supporting the hypothesis that PIVH causes impairment in neuropsychomotor development in our meta-analysis, but review of newer studies show an increased risk for lower intelligence scores in children with severe lesions, both PIVH and PVL. There is evidence to support the hypothesis that children with any degree of PIVH, especially those born below 1000 grams and those with severe haemorrhage, are at increased risk of developing CP, as well as children with PVL, both cystic and non-cystic.
Topics: Cerebral Hemorrhage; Hearing Loss; Humans; Infant, Newborn; Infant, Premature; Leukomalacia, Periventricular; Nervous System; Treatment Outcome; Vision Disorders
PubMed: 31600248
DOI: 10.1371/journal.pone.0223427 -
Expert Opinion on Investigational Drugs Mar 2022Periventricular leukomalacia (PVL) is a result of various antenatal, intrapartum, or postnatal insults to the developing brain and is an important harbinger of cerebral...
INTRODUCTION
Periventricular leukomalacia (PVL) is a result of various antenatal, intrapartum, or postnatal insults to the developing brain and is an important harbinger of cerebral palsy in preterm neonates. There is no proven therapy for PVL. This calls for appraisal of targeted therapies that have been investigated in animal models to evaluate their relevance in a clinical research context.
AREAS COVERED
This systematic review identifies interventions that were evaluated in preclinical studies for neuroprotective efficacy against PVL. We identified 142 studies evaluating various interventions in PVL animal models (search method is detailed in section 2).
EXPERT OPINION
Interventions that have yielded significant results in preclinical research, and that have been evaluated in a limited number of clinical trials include stem cells, erythropoietin, and melatonin. Many other therapeutic modalities evaluated in preclinical studies have been identified, but more data on their neuroprotective potential in PVL must be garnered before they can be considered for clinical trials. Because most of the tested interventions had only a partial efficacy, a combination of interventions that could be synergistic should be investigated in future preclinical studies. Furthermore, since the nature and pattern of perinatal insults to preterm brain predisposing it to PVL are substantially variable, individualized approaches for the choice of appropriate neuroprotective interventions tailored to different subgroups of preterm neonates should be explored.
Topics: Animals; Brain; Female; Humans; Infant, Newborn; Leukomalacia, Periventricular; Pregnancy; Risk Factors
PubMed: 35143732
DOI: 10.1080/13543784.2022.2040479