Neonatal Periventricular Leukomalacia Research Articles

Effects of Antenatal Steroids with Magnesium Sulphate on Intraventricular Hemorrhage and Periventricular Leukomalacia in Neonates Born below 32 Weeks of Gestation

Introduction: The most important acquired brain injuries in very and extremely preterm infants born in developing Country are periventricular-Intraventricular haemorrhages and diffuse white matter injury. Antenatal corticosteroids play a crucial role in its development. A study was conducted to determine effects of antenatal steroids along with magnesium sulphate on Intraventricular Hemorrhage and Periventricular Leukomalacia in preterm neonates.
 Methodology: A retrospective prospective cohort study conducted among premature newborn babies admitted in the hospital. Based on the antenatal medication subjects were divided in to three groups: Group 1: No Steroid and No MgsO4 in antenatal period; Group 2: Received complete and incomplete course of antenatal steroid; and Group 3: Received complete course of antenatal steroid and MgSO4. The Occurrence of IVH and/or PVL in the neonates during hospital stay in all 3 groups.
 Results: Among the 144 cases, 8 patients had IVH and 1 had PVL. No intervention group (No antenatal steroids/ antenatal MgSo4) had highest chances of development of IVH/PVL. Significantly lower rate of IVH/PVL recorded in ‘Steroid and MgSO4’ group compared to only ‘Steroid’ group. The chances of development of RDS, BPD and NEC in no intervention group (No antenatal steroids and antenatal MgSo4) was significantly higher compared to steroid and and MgSO4 group and Steroid only group.
 Conclusion: This study confirmed that antenatal steroids when used along with antenatal magnesium sulphate to deliver preterm babies reduce IVH and white matter brain injury significantly.

Prediction of Periventricular Leukomalacia in Neonates after Cardiac Surgery Using Machine Learning Algorithms.

Periventricular leukomalacia (PVL) is brain injury that develops commonly in neonates after cardiac surgery. Earlier identification of patients who are at higher risk for PVL may improve clinicians' ability to optimize care for these challenging patients. The aim of this study was to apply machine learning algorithms and wavelet analysis to vital sign and laboratory data obtained from neonates immediately after cardiac surgery to predict PVL occurrence. We analyzed physiological data of patients with and without hypoplastic left heart syndrome (HLHS) during the first 12h after cardiac surgery. Wavelet transform was applied to extract time-frequency information from the data. We ranked the extracted features to select the most discriminative features, and the support vector machine with radial basis function as a kernel was selected as the classifier. The classifier was optimized via three methods: (1) mutual information, (2) modified mutual information considering the reliability of features, and (3) modified mutual information with reliability index and maximizing set's mutual information. We assessed the accuracy of the classifier at each time point. A total of 71 neonates met the study criteria. The rates of PVL occurrence were 33% for all patients, with 41% in the HLHS group and 25% in the non-HLHS group. The F-score results for HLHS patients and non-HLHS patients were 0.88 and 1.00, respectively. Using maximizing set's mutual information improved the classifier performance in the all patient groups from 0.69 to 0.81. The novel application of a modified mutual information ranking system with the reliability index in a PVL prediction model provided highly accurate identification. This tool is a promising step for improving the care of neonates who are at higher risk for developing PVL following cardiac surgery.

Neonatal periventricular leukomalacia: current perspectives

Neonatal periventricular leukomalacia: current perspectives Kunal P Ahya,1 Pradeep Suryawanshi2 1Department of Neonatology, Maahi Newborn Care Centre, Rajkot, Gujarat, 2Department of Neonatology, BVDU Medical College, Pune, Maharashtra, India Abstract: Significant advances in the neonatal ICU have improved the survival of extreme premature neonates; with this comes the importance of intact survival. Periventricular leukomalacia (PVL) is the commonest white matter brain injury in preterm infants. It has a typical distribution at the watershed areas adjacent to the lateral ventricles. PVL occurs because of ischemic injury to periventricular oligodendrocytes of the developing brain. It can be detected by cranial ultrasonography (CUS) as initial periventricular echodensities, followed later by cystic formation. Recent magnetic resonance imaging studies have shown that it helps in early visualization of PVL and also detection of non-cystic form of PVL, which is not picked up by CUS. It is the commonest cause of cerebral palsy, intellectual impairment or visual disturbances. Currently, no medical treatment is available for PVL; prevention and close developmental follow-up are the only options. Keywords: periventricular leukomalacia, preterm brain injury, cranial ultrasonography

Antenatal corticosteroids for neonates born before 25 Weeks-A systematic review and meta-analysis.

BackgroundEfficacy of antenatal corticosteroids before 25 weeks of gestation is unclear.ObjectiveTo assess and compare neonatal outcomes following ANC exposure at 22, 23 and 24 weeks of gestation by conducting systematic review and meta- analysis.MethodsA systematic review of randomised controlled trials (RCT) and non-RCTs reporting on neonatal outcomes after exposure to ANC up to 246 weeks of gestation using the Cochrane systematic review methodology. Databases Pubmed, CINAHL, Embase, Cochrane Central library, and online abstracts of conference proceedings including the Pediatric Academic Society (PAS) were searched in Feb 2017. Primary outcome was in-hospital mortality defined as death before discharge during the first admission. Secondary outcomes included severe intraventricular hemorrhage (IVH> grade III and IV)/or periventricular leukomalacia (PVL), necrotising enterocolitis (NEC >stage II) and chronic lung disease (CLD). Meta-analysis was performed using a random-effects model. The level of evidence (LOE) was summarised using the GRADE guidelines.Main resultsThere were no RCTs; 8 high quality non-RCTs were included in the review. Meta-analysis showed reduction in mortality [N = 10109; OR = 0.47(0.39–0.56), p<0.00001; LOE: Moderate] and severe IVH and PVL [N = 5084; OR = 0.71(0.61–0.82), p<0.00001; LOE: Low] after exposure to ANC in neonates born <25 weeks. There was no significant difference in CLD [N = 4649; OR = 1.19(0.85–1.65) p = 0.31; LOE: Low] and NEC [N = 5403; OR = 0.95 (0.76–1.19) p = 0.65; LOE: Low]. Mortality was comparable in neonates born at 22, 23 or 24 weeks.ConclusionModerate to low quality evidence indicates that exposure to ANC is associated with reduction in mortality and IVH/or PVL in neonates born before 25 weeks.

A model of Periventricular Leukomalacia (PVL) in neonate mice with histopathological and neurodevelopmental outcomes mimicking human PVL in neonates.

Periventricular leukomalacia (PVL), a brain injury affecting premature infants is commonly associated with cerebral palsy. PVL results from hypoxia-ischemia (HI) with or without infection and is characterized by white matter necrotic lesions, hypomyelination, microglial activation, astrogliosis, and neuronal death. It is important to study a PVL mouse model that mimics human PVL in symptomatology, anatomic and molecular basis. In our neonate mice model, bilateral carotid arteries were temporary ligated at P5 followed by hypoxic exposure (FiO2 of 8% for 20 min.). At P5 in mice, the white matter is more vulnerable to HI injury than the grey matter. In our PVL model, mice suffer from significant hind limb paresis, incoordination and feeding difficulties. Histologically they present with ventriculomegally, white matter loss, microglial activation and neuronal apoptosis. HI injury increases proinflammtory cytokines, activates NF-kB, activates microglia and causes nitrative stress. All these inflammatory mediators lead to oligodendroglial injury and white matter loss. Neurobehavioral analysis in the PVL mice model at P60 showed that the HI group had a significant decrease in hind limb strength, worsening rotarod testing and worsening performance in the open field test. This new PVL model has great advantages far beyond just mimicking human PVL in clinical features and histopathology. Long term survival, the development of cerebral palsy and the ability of using this model in transgenic animals will increase our understanding of the mechanistic pathways underlying PVL and defining specific targets for the development of suitable therapeutics.

Pentoxifylline for treatment of sepsis and necrotizing enterocolitis in neonates.

Mortality and morbidity due to neonatal sepsis and necrotizing enterocolitis (NEC) remain high despite the use of potent antimicrobial agents. Agents that modulate inflammation may improve outcomes. Pentoxifylline, a phosphodiesterase inhibitor, is one such agent. Our primary objectives were :1.To assess the effect of intravenous pentoxifylline as an adjunct to antibiotic therapy on mortality and morbidity in neonates with suspected or confirmed sepsis.2.To assess the effect of intravenous pentoxifylline as an adjunct to antibiotic therapy on mortality and morbidity in neonates with NEC. We searched the Cochrane Neonatal Review Group Specialized Register, CENTRAL (The Cochrane Library Issue 2, 2014), EMBASE (January 1980 to May 2014), PubMed (January 1966 to May 2014), CINAHL (January 1982 to May 2014), Science Citation Index (January 1990 to May 2014), and BIOSIS (January 1992 May 2014) in May 2014. We checked references and cross-references from identified studies. We handsearched abstracts from the proceedings of the Pediatric Academic Societies Meetings (from January 1990 to May 2014). We placed no restrictions on language. We included randomised or quasi-randomised trials assessing the efficacy of pentoxifylline as an adjunct to antibiotics for treatment of suspected or confirmed sepsis or NEC in neonates. We reported typical risk ratio (RR) and risk difference (RD) with 95% confidence intervals (CI) using fixed-effect model for dichotomous outcomes and mean difference (MD) for continuous outcomes. We calculated the number needed to treat for an additional beneficial outcome (NNTB) if there was a statistically significant reduction in RD. Pentoxifylline used as an adjunct to antibiotics in neonates with sepsis decreased all-cause mortality during hospital stay (typical RR 0.57, 95% CI 0.35 to 0.93; typical RD -0.08, 95% CI -0.14 to -0.01; NNTB 13, 95% CI 7 to 100; 6 studies, 416 participants, low-quality evidence). Subgroup analyses revealed decrease in mortality in preterm infants, infants with confirmed sepsis, and infants with gram-negative sepsis (low-quality evidence, four studies). Pentoxifylline decreased length of hospital stay (MD -7.59 days, 95% CI -11.65 to -3.52; 2 studies, 148 participants, low-quality evidence). Pentoxifylline did not change the risk of development of NEC, chronic lung disease, severe intraventricular haemorrhage, retinopathy of prematurity, or periventricular leukomalacia in neonates with sepsis (one to two studies, very low-quality evidence). Pentoxifylline therapy compared to pentoxifylline and immunoglobulin M-enriched intravenous immunoglobulin or immunoglobulin M-enriched intravenous immunoglobulin alone did not change mortality or development of NEC in neonates with sepsis (one study, very low-quality evidence). We noted no adverse effects due to pentoxifylline. We identified no trials evaluating pentoxifylline treatment for NEC. Low-quality evidence from six small studies suggests that pentoxifylline therapy as an adjunct to antibiotics in neonatal sepsis decreases mortality without any adverse effects. We encourage researchers to undertake large, well-designed multicentre trials to confirm or refute the effectiveness of pentoxifylline in reducing mortality and morbidity in neonates with sepsis or NEC.

Cranial Ultrasonography and Doppler in Preterm and Term Neonates

Aims And Objective: Role of cranial ultrasonography to evaluate intracranial abnormalities in preterm and term neonates.  To ascertain the clinical course of intracranial haemorrhage and to determine the short- term outcome of the affected baby neonates who develop intracranial complications of prematurity.  The utility of real-time ultrasonography in the diagnosis of neonatal periventricular leukomalacia. To asses utility of cranial colour Doppler in preterm and term neonates.  To evaluate cerebral blood flow velocities in ACA, MCA and PCA in preterm and term neonates.  To evaluate developmental interval changes in cerebral postnatal hemodynamic variation in the blood flow velocities in the preterm and term neonates. Method: Grey scale imaging for intracranial abnormalities and colour Doppler evaluation of intracranial arteries were done on neonates between 3 to 5 days, 10 to 14 days and 26 to 30 days after birth. RESULT: The study was conducted in the department of radiodiagnosis in Adichunchangiri Institute Of Medical Sciences. Prospective radiological clinical study with 52 neonates was undertaken to study the Cranial ultrasonography and Doppler in Preterm ( 37 weeks).On cranial USG , 15 (28.8%) neonates revealed no abnormality, 12(23.1%) showed PVHE , 11(21.2%)neonates showed ICH, 6(11.5%) neonates showed PVL, 4(7.7%) neonates showed Cysts , 4(7.7%) neonates had cerebral edema. On cranial Doppler evaluation of ACA, MCA and PCA progressive rise in systolic and diastolic velocities were seen with increasing gestational age and increasing age of the neonate. The rate of increase in velocity was greater with increasing gestational age. The resistive index decreased progressively with gestational age and with increasing age of the neonate. Conclusion: Neonatal cranial ultrasonography is the easiest and most ideal investigation for diagnosing intracranial pathologies in preterm and term neonates. Neonatal cranial Doppler provides a reliable means to evaluate changes in the intracerebral blood flow with a variety of intracranial pathologies.

A Proposal to Reduce Congenital Cerebral Palsy

Aims: To clarify the feasibility to arrest preterm labor to prevent the periventricular leukomalacia (PVL) and Cerebral Palsy (CP) by the study on the developing mechanism of labor contractions. Rational: Fetal periventricular echo density (PVE) precedes preterm neonatal PVL and CP in 18% of preterm fetuses whose PVE persisted until preterm births. Since no treatment of neonatal PVE appeared immediately after preterm birth was established, another strategy is proposed to prevent preterm neonatal PVE to cease preterm labor until the full term delivery, because no CP developed in full term delivery in our report. Recently, we studied the positive feed-back loop of uterine contraction to the brain by nerves between the uterus and hypothalamus, developing regular labor contractions. Proposal: The suppression of the nerves of positive feed-back loop by anesthesia or analgesia is our proposal to cease preterm labor until the full term delivery, where no CP was reported, i.e. the CP, corresponding to 0.2% of total births, will be reduced. Conclusion: Regular preterm labor contractions will be ceased by the paralysis of nerves in the positive feed-back loop between the uterus and hypothalamus and the full-term delivery prevents CP, due to disappeared PVE in the neonates born in full term delivery. Clinical feasibility should be investigated in further studies.

Neonatal periventricular leukomalacia without evidence of twin-to-twin transfusion syndrome following discordance in nuchal translucency: a case report.

We describe a case of neonatal periventricular leukomalacia (PVL) without evidence of twin-to-twin transfusion syndrome (TTTS) following discordance in nuchal translucency (NT). A 34-year-old woman with monochorionic twins after in-vitro fertilization and embryo transfer was referred to our hospital. At gestational week 11, fetus A showed increased NT (7.0mm) and normal crown-rump length (CRL) (34.3mm). Fetus B had normal values, with a NT of 1.3mm and a CRL of 32.3mm. Both twins maintained growth throughout pregnancy, with no evidence of TTTS. During the antepartum period, daily fetal heart rate monitoring showed a reassuring pattern. Cesarean delivery was performed in gestational week 32. Neonates A and B weighed 2,071 and 1,617g, respectively (discordancy rate 21.9%), each with an Apgar score of 8 at 1min. Soon after birth, brain ultrasonography of neonate A revealed high-echoic periventricular lesions bilaterally, and brain magnetic resonance imaging on day 7 revealed PVL. Neonate B showed completely unremarkable results.

Periventricular Leukomalacia and Placental Histopathologic Abnormalities

To estimate whether there are placental histopathologic abnormalities associated with neonatal periventricular leukomalacia (PVL), a major precursor of cerebral palsy. This is a case-control study of 167 neonates born between 23 and 34 weeks of gestation diagnosed with PVL by head ultrasonography within 6 weeks of birth, and 167 control neonates without neurologic morbidity matched by gestational age. Placentas for both case neonates and control neonates were reviewed by two perinatal pathologists who were blinded to neonatal course. Neonates with PVL were significantly more likely to have positive neonatal blood (28.7%, 16.8%, P=.001) and cerebrospinal fluid (14.4%, 4.8%, P=.007) cultures. The ratio of placental weight to birth weight did not differ between groups, but neonates with PVL had significantly more chronic diffuse capsular deciduitis (20.4%, 10.8%, P=.02) and capsular decidual plasma cells (8.4%, 2.4%, P=.02). Conditional logistic regression adjusting for birth weight and the presence of multiple gestation in the identification of PVL showed a significant increase for diffuse capsular deciduitis (P=.02) and capsular decidual plasma cells (P=.03). Periventricular leukomalacia has a significant but weak association with chronic diffuse capsular deciduitis and the presence of capsular decidual plasma cells, evidence of chronic infection but not histologic acute chorioamnionitis. II.

Maternal plasma interleukin-6, interleukin-1β and C-reactive protein as indicators of tocolysis failure and neonatal outcome after preterm delivery

Objective. To investigate whether maternal serum interleukin-6 (IL-6), interleukin-1β (IL-1β) and high sensitive C-reactive protein (CRP) could be used as markers of tocolysis failure and adverse neonatal outcome in pregnancies with preterm labor (PL).Methods. Forty-seven maternal blood samples taken because of PL at admission and delivery were analyzed. Control samples were taken from 20 gravidas with normal pregnancies. Differences in interleukins and CRP levels with or without chorioamnionitis, connatal infection or periventricular leukomalacia (PVL) were analyzed. Cut-off values were estimated for prediction of tocolysis failure and adverse neonatal outcome.Results. All three parameters were significantly higher in patients delivering prematurely than in patients delivering at term. All three parameters were significantly higher with than without histologic chorioamnionitis (p < 0.001), with than without connatal infection (p < 0.01), with than without PVL (p < 0.01 for IL-6 and IL-1β, p < 0.05 for CRP), and in pregnancies with preterm premature rupture of membranes (PPROM) delivered within 48 hours compared to those more prolonged (p < 0.01). Choosing 50.9 pg/mL of IL-6 and a CRP of 19.7 as cut-offs in maternal blood admission concentrations for neonatal PVL, resulted in sensitivity of 81% and specificity of 91% and sensitivity of 91% and specificity of 81%, respectively. At respective maternal blood admission cut-off levels of 27.8 pg/mL of IL-6 and 8.9 of CRP, both parameters were effective predictors of connatal infection.Conclusions. Maternal blood IL-6 and CRP could become useful in predicting tocolysis failure and intrauterine treat for the fetus.

Antenatal steroids and neonatal periventricular leukomalacia

Objective: To evaluate the effect of antenatal steroid treatment on the development of neonatal periventricular leukomalacia. Methods: This retrospective cohort study included 1161 neonates with gestational ages of 24–34 weeks and birth weights of 500–1750 g, divided into two groups on the basis of antenatal steroid treatment. Neonatal neurosonograms were done on days 3 and 7 of life and labeled normal or abnormal. The abnormal outcomes evaluated were periventricular leukomalacia or intraventricular hemorrhage, periventricular leukomalacia with intraventricular hemorrhage, and isolated periventricular leukomalacia. The group treated with antenatal steroids was compared with the untreated group for these outcomes. Results: Antenatal steroids were associated with significantly less periventricular leukomalacia or intraventricular hemorrhage (23% versus 31%, P = .005), periventricular leukomalacia with intraventricular hemorrhage (5% versus 11%, P = .001), and isolated periventricular leukomalacia (3% versus 7%, P = .009). Logistic regression analysis of antenatal steroid treatment, controlling for confounding maternal and neonatal characteristics, indicated that neonates treated with antenatal steroids had a 56% lower likelihood of periventricular leukomalacia with intraventricular hemorrhage (adjusted odds ratio [OR] 0.44, 95% confidence interval [CI] 0.25, 0.77) and a 58% lower likelihood of isolated periventricular leukomalacia (adjusted OR 0.42, 95% CI 0.20, 0.88). Conclusion: Antenatal steroid treatment was associated with over 50% reduction in the incidence of periventricular leukomalacia in preterm neonates. Increased use of antenatal steroid therapy might improve long-term neonatal neurologic outcomes.