Periventricular Leukomalacia In Preterm Infants Research Articles

Neonatal seizure caused by periventricular leukomalacia resulting from maternal protein S deficiency and treated with aspirin

Periventricular leukomalacia (PVL) is a white matter injury that mostly occurs with prematurity at the gestational age (GA) of 24–32 weeks and birth weight below 1500 g. A major cause of PVL is neonatal hypoxic ischemia and/or hemorrhage around the ventricles of the brain, which could lead to neonatal seizure.1 The incidence of PVL in preterm infants declines with increasing GA.2 This report presents the case of a near-term neonate at GA of 36 4/7 weeks who had neonatal seizure at the age of 1.5 months and whose brain image showed significant bilateral PVL.

Risk Factors for Periventricular Leukomalacia in Preterm Infants: A Systematic Review, Meta-analysis, and GRADE-Based Assessment of Certainty of Evidence

BackgroundWe analyzed the certainty of evidence (CoE) for risk factors of periventricular leukomalacia (PVL) in preterm neonates, a common morbidity of prematurity. MethodsMedline, 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. ResultsOne 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. ConclusionDespite 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.

Association between perinatal hypoxic-ischemia and periventricular leukomalacia in preterm infants: A systematic review and meta-analysis.

BackgroundAlthough 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.MethodThe 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.ResultsFifteen 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.ConclusionThis 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.

Risk Factors of Cystic Periventricular Leukomalacia in Preterm Infants with Gestational Ages of Less Than 32 Weeks according to Gestational Age Group

Purpose: The aim of the study was to determine the incidence of cystic periventricular leukomalacia (PVL) and identify the risk factors for cystic PVL in preterm infants with gestational age (GA) less than 32 weeks according to gestational age group. Methods: The medical records and brain imaging were reviewed for preterm infants with less than 32 weeks GA who lived more than 4 weeks and admitted to the neonatal intensive care unit at Inje University Sanggye Paik Hospital from January 2009 to June 2015. We determined the incidence and the risk factors for the development of cystic PVL in preterm infants according to GA group. Results: Incidence of cystic PVL was 15.1% (26/172). Multivariate analysis showed that intraventricular hemorrhage (IVH) [P=0.006, odds ratio (OR) 5.478, 95% confidence interval (CI) 1.641-18.285), oxygen uses over 28 days (P=0.025, OR 3.086, 95% CI 1.152-8.264), and NEC (P=0.042, OR 3.731, 95% CI 1.047-13.333) were independent risk factors for the developmental of cystic PVL. Subgroup analysis showed that pregnancyinduce hypertension and IVH were independent risk factors in preterm infants with GA of less than 28 weeks. Also, oxygen uses over 28 days and culture proven sepsis were independent risk factors in preterm infants with GA of 28 +0 -31 +6 weeks. Conclusion: These results suggest that pregnancy-induce hypertension and IVH may increase the risk for the subsequent development of cystic PVL in preterm infants with GA of less than 28 weeks, and oxygen uses over 28 days and culture proven sepsis may increase in preterm infants with GA of 28 +0 -31 +6 weeks.

Microglia and white matter injury in preterm infants

Periventricular leukomalacia in premature infants is the most common brain injury.It often results in spastic cerebral palsy,cognitive and behavioral abnormalities and other sequelae.The microglia is the primary immune response cell in brain,and it plays an important role in balancing mechanism for the defense response and brain injury.The suppression of its activated reaction can reduce the cytotoxic effect and pathological damage in the early phase. Key words: Premature infants; White matter damage; Microglial cells

A comparative study on the diagnostic value of craniocerebral ultrasound versus that DWI in premature infants with periventricular leukomalacia

Objective To compare the diagnostic value of craniocerebral ultrasound with that of diffusion weighted imaging ( DWI )in premature infante with periventricular leukomalacia ( PVL ). Methods Diagnostic ultrasound and DWI were performed on premature infants with PVL. Results The positive rate of early detecting PVL in premature infants differed significantly between craniocerebral ultrasound and DWI ( 20.8% for craniocerebral ultrasound vs. 52.6% for DWI; x2=10.93, P< 0.01 ). Conclusions DWI is more sensitive than craniocerebral ultrasound in the ealy diagnosis of PVL in premature infants. Premature infants should receive DWI as early as possible ( within 1 week after birth). Key words: Periventricular; Leukomalacia; Premature infant; Ultrasound; DWI; Comparative study

‘‘Intraventricular’’ Hemorrhage and Cystic Periventricular Leukomalacia in Preterm Infants: How Are They Related?

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.

Does hypoxic vasoconstriction influence the normal distribution of human pulmonary blood flow?

elevation of regional pulmonary resistance in response to local alveolar hypoxia is a near-universal response of the mammalian lung to optimize arterial oxygenation ([14][1]). Given the heterogeneity of regional ventilation observed in a normal lung ([11][2], [16][3]), it appears plausible that

Studies on the Value of Diffusion‐Weighted MR Imaging in the Early Prediction of Periventricular Leukomalacia

Periventricular leukomalacia (PVL) is the most common cerebral injury in premature infants. While cranial ultrasonography and conventional magnetic resonance imaging (MRI) offer little for its early diagnosis, still they are much favored at present. Based on the pathologic mechanism of ischemic cerebral injury in PVL, we attempt to elucidate the effects of diffusion-weighted MR imaging (DWI) for the early diagnosis of PVL. Twelve cases of PVL in premature infants confirmed by MRI examinations were included in the current study. All cases underwent DWI in addition to conventional MR imaging (T1-weighted [T1W] and T2-weighted [T2W]) 7 days, 2 weeks, and 4 approximately 8 weeks after birth, respectively. Initial DWI examination (carried out at an average of 4.5 days after birth) revealed symmetrical and diffuse high signal in bilateral periventricular areas in all cases, while conventional MRI demonstrated normal signal. DWI examination of 2 weeks later showed irregular inhomogeneous signals in cerebral white matter, while conventional MRI revealed hyperintensity on T1WI and slight hypointensity on T2WI in corresponding areas. Four weeks later, DWI revealed various intensities of cystic low signals beside lateral ventricles, while conventional MRI showed hypointensity on T1WI and hyperintensity on T2WI in corresponding lesion, ie, change in cystic PVL. Four months later, conventional MRI evidenced gradual shrink and disappearance of cystic cavity, reduction in cerebral white matter, and ventricle enlargement. Symmetrical, diffuse hyperintensity in both lateral periventricular white matter on DWI was the earliest sign of PVL in premature infants. Imaging abnormalities provided by DWI had a close correlation with the results obtained by conventional MRI performed at the advanced stage of PVL, which suggests that DWI may be an important sequence for the early evaluation of cerebral white matter injury as well as for the prediction of PVL occurrence in premature infants.

105: Histopathological placental features associated with development of periventricular leukomalacia in preterm infants

105: Histopathological placental features associated with development of periventricular leukomalacia in preterm infants

Obstetric Risk Factors Associated with the Development of Periventricular Leukomalacia in Preterm Infants Born to Mothers Complicated by Placenta Previa

Objectives: This study was designed to evaluate the effect of antenatal risk factors on the occurrence of periventricular leukomalacia (PVL) in preterm infants from pregnancies complicated by placenta previa. Study Design: The association between obstetric risk factors and PVL was assessed in 30 singleton live births complicated with placenta previa delivered between 24 and 33 completed weeks of gestation. Each infant underwent at least two cranial ultrasounds: the first before 72 h and the second around 14 days of life. Analysis of variance was used to compare continuous variables across groups. Comparison of groups for categorical data was analyzed with Pearson χ² test. Results: The obstetric factors in infants with PVL were compared to those in infants with negative cranial ultrasonographic findings. The main risk factors for PVL in preterm placenta previa were initial antepartum hemorrhage <28 weeks of gestation (OR 13.7; 95% CI 1.38–136.2), although the differences of gestational age of delivery between two groups were not statistically significant. Low Apgar score (<7) at 1 min increased the risk of PVL (OR 8.89; 95% CI 12.9–61.1), while no associations with PVL were observed in low Apgar score at 5 min, neonatal acidosis (pH <7.2), and neonatal anemia (Hb <14 g/dl). Conclusions: This study demonstrates that initial antepartum hemorrhage during the second trimester and low Apgar score at birth increase the risk of PVL in preterm infants born to mothers with placenta previa. We speculate that the pathophysiologic mechanisms for this finding may be due to decreased placental perfusion in the second trimester of pregnancy, which is the developmental window of vulnerability for PVL.

Periventricular Leukomalacia in Premature Infants in Mainland China

Periventricular leukomalacia (PVL) in premature infants is a major cause of mortality and disability. However, while China is the largest developing country, there is an absence of data concerning PVL. This study was carried out in order to explore the incidence rate and analyze the high-risk factors of PVL in premature infants, and to suggest a working protocol for the prevention of PVL in newborns at risk. The cohort prospective study included 921 premature infants < 37 weeks' gestation from January 2004 to July 2007. The study group was comprised of 271 premature infants with an ultrasound diagnosis of PVL and the control group was comprised of 650 premature infants who were submitted to the same evaluation protocol but did not show any echographic signs of PVL. The results showed that the incidence rate of PVL was 29.4% in China. High-degree PVL accounted for < 12% and > 88% of PVL was low-degree. The incidence rate was much higher when premature infants were accompanied by the following complications: low gestational age, low birth weight, prolonged rupture of membranes, chorionitis, mechanical ventilation, periventricular-ventricular hemorrhage, hypocapnia, and hyperlactacidemia. Severe complications that occur in premature infants also significantly increase the incidence of PVL. Antenatal corticosteroids can significantly decrease the incidence rate of PVL. This investigation provided a theoretical reference for the prevention of premature PVL.

Cystic periventricular leukomalacia in preterm infants: An analysis of obstetric risk factors

Objective To identify obstetric risk factors and to elucidate the effect of prolonged rupture of the membranes on the development of cystic periventricular leukomalacia (PVL) in preterm infants. Methods A retrospective case–control study of 95 preterm infants with the diagnosis of PVL and 245 healthy controls matched for gestational age. A total of 52 antenatal, intrapartum and neonatal characteristics were studied by univariate methods and logistic regression. Results Preterm premature rupture of membranes (PPROM) (odds ratio 2.1 [95% CI 1.3–3.4], P = .003), gestational age at PPROM ( P = .025), prolonged rupture of membranes ( P < .0001), administration of tocolytic agents (1.8 [1.1–3.0], P = .019) and antibiotics (1.9 [1.2–3.1], P = .008) were associated with PVL. The use of tocolytic agents > 24 h ( P = .008), prolonged latency between the increase in maternal leukocyte count and birth ( P = .034), spontaneous onset of labor (1.8 [1.0–2.9], P = .026), vaginal delivery (1.7 [1.1–2.8], P = .029) and male gender (1.5 [1.0–2.0], P = .04) were found more frequently in PVL cases. Preeclampsia (0.4 [0.1–0.9], P = .034), hypertension at booking ( P = .009), sonographic IUGR ( P = .020), abnormal blood flow of the umbilical artery ( P = .032) and cesarean section without labor (0.5 [0.3–0.8], P = .006) were found less frequently. In logistic regression analysis, prolonged rupture of the membranes ( P = .748), preeclampsia ( P = .973), the use of antibiotics ( P = .617) and beta-sympathomimetic tocolytic agents ( P = .563) lost statistical significance, whereas birth weight ( P = .036) became significant. Conclusion PPROM and prolonged rupture of the membranes may provoke adverse effects on the neurodevelopmental outcome of the preterm fetus. These findings may have implications on the obstetric management of PPROM beyond 30 weeks of gestation. Cesarean section without labor was less likely associated with the diagnosis of PVL.

Progress in imaging diagnosis of periventricular leukomalacia in preterm infants

脑室周围白质软化(PVL)是早产儿脑损伤的主要形式,包括囊性和弥漫性PVL.近年来其发病率有逐渐增高趋势,已成为影响早产儿生存质量及导致小儿脑瘫的主要疾病.因早产儿PVL缺乏特异的临床表现,故其诊断必须依赖于影像学检查.B超是目前确诊PVL最常用的检测手段,但其漏诊率较高;常规磁共振成像对评价PVL的脑损伤程度及预后判定具有重要意义,但在早期,特别是对弥漫性PVL也有其局限性;而弥散加权成像作为一种新型的检测技术,弥补了B型超声及常规磁共振成像的不足,为弥漫性PVL早期诊断提供了有价值的影像学信息。

Pharmacological and genetic inhibition of NADPH oxidase does not reduce brain damage in different models of perinatal brain injury in newborn mice

Background Inflammation and reactive oxygen species (ROS) are important in the development of perinatal brain injury. The ROS-generating enzyme NADPH oxidase (Nox2) is present in inflammatory cells and contributes to brain injury in adult animal models. Hypothesis NADPH oxidase contributes to ROS formation and development of injury in the immature brain and inhibition of NADPH oxidase attenuates perinatal brain injury. Methods We used animal models of term hypoxia–ischemia (HI) (P9 mice) as well as ibotenate-induced excitotoxic injury (P5 mice) mimicking features of periventricular leukomalacia in preterm infants. In vitro microglia cell cultures were used to investigate NADPH oxidase-dependent ROS formation. In vivo we determined the impact 1) of HI on NADPH oxidase gene expression 2) of genetic (gp91-phox/Nox2 knock-out) and 3) of pharmacological NADPH oxidase inhibition on HI-induced injury and NMDA receptor-mediated excitotoxic injury, respectively. Endpoints were ROS formation, oxidative stress, apoptosis, inflammation and extent of injury. Results Hypoxia–ischemia increased NADPH oxidase subunits mRNA expression in total brain tissue in vivo. In vitro ibotenate increased NADPH oxidase-dependent formation of reactive oxygen species in microglia. In vivo the inhibition of NADPH oxidase did not reduce the extent of brain injury in any of the animal models. In contrast, the injury was increased by inhibition of NADPH oxidase and genetic inhibition was associated with an increased level of galectin-3 and IL-1β. Conclusion NADPH oxidase is upregulated after hypoxia–ischemia and activated microglia cells are a possible source of Nox2-derived ROS. In contrast to findings in adult brain, NADPH oxidase does not significantly contribute to the pathogenesis of perinatal brain injury. Results obtained in adult animals cannot be transferred to newborns and inhibition of NADPH oxidase should not be used in attempts to attenuate injury.

A Pilot Study on Cord Blood Levels of Erythropoietin and Its Relationship to Periventricular Leukomalacia in Preterm Infants

This article reports the results of a study on the relationship between cord blood levels of erythropoietin and periventricular leukomalacia. Cord blood was obtained from 19 infants with gestational age between 27 and 32 weeks. Cystic periventricular leukomalacia was seen in 4 of them. Erythropoietin levels were not different between those with and those without periventricular leukomalacia.

Quel risque néonatal pour les grossesses à bas risque : implications pédiatriques pour l'organisation des maisons de naissance ?

Aim This study was designed to identify pregnant women at low risk for severe neonatal morbidity. This population should apply for delivery in birth centers. Population and methods This study was retrospective and included all livebirths in Burgundy over a 4-year period. Fifteen obstetric criteria recorded in the regional perinatal database were used to select pregnant women at low risk for severe neonatal morbidity. Incidence of severe neonatal morbidity in the low and high risk groups was assessed from the following markers: postnatal death; severe neurological conditions (ischemic encephalopathy, seizures, meningitis, intraventricular hemorrhage stage 3–4 and cystic periventricular leukomalacia in preterm infants) ; tracheal intubation ; hospitalization in neonatal intensive care unit. Results The incidence of severe neonatal morbidity was significantly different ( P < 0.0001) in the low risk group (0.34% [IC 95%: 0.29–0.40]; N = 46 345) as compared with the high risk group (5.6% [IC 95%: 5.3–5.9]; N = 24 961). The main neonatal diseases in the low risk group were: respiratory diseases (29.8%); congenital heart diseases (17.9%) and perinatal asphyxia (15.3%). Conclusion Even though the low risk criteria were associated with a low incidence of severe neonatal morbidity, residual morbidity should be considered in organization of birth centers in France.

High risk factors of cystic periventricular leukomalacia in preterm infants

目的 探讨早产儿囊性脑室周围白质软化症(cPVL)的高危因素.方法 对cPVL(12例)与非cPVL早产儿(30例)进行回顾性研究,对多种围产期高危因素进行Logistic回归分析.结果 胎膜早破、生后48 h内PaCO2＜3.33 kPa(25 mm Hg)、生后4 h内pH＜7.25、生后1周内发现脑室周围强回声的OR值分别为2.125、3.312、2.820和3.712(P＜0.05或P＜0.01).结论 胎膜早破、生后48 h内PaCO2＜3.33 kPa、生后4h内pH＜7.25、生后1周内脑室周围有强回声为早产儿cPVL的高危因素。

Association between IL-6–174 (G/C) polymorphism and cystic periventricular leukomalacia in preterm infants

Association between IL-6–174 (G/C) polymorphism and cystic periventricular leukomalacia in preterm infants

Association between IL-6–174 (G/C) polymorphism and cystic periventricular leukomalacia in preterm infants

Association between IL-6–174 (G/C) polymorphism and cystic periventricular leukomalacia in preterm infants