Development Of Cerebral Palsy Research Articles

Optimization of Maternal Magnesium Sulfate Administration for Fetal Neuroprotection: Application of a Prospectively Constructed Pharmacokinetic Model to the BEAM Cohort.

The aim of the study was to identify the optimal therapeutic maternal magnesium drug exposure and maternal serum concentration to prevent cerebral palsy in the extremely preterm fetus. We applied a previously constructed pharmacokinetic model adjusted for indication to a large cohort of pregnant women receiving magnesium sulfate to prevent cerebral palsy in their preterm offspring at 20 different US academic centers between December 1997 and May 2004. We simulated the population-based individual maternal serum magnesium concentration at the time of delivery and the total magnesium dose for each woman who received magnesium sulfate to determine the relationship between maternal serum magnesium level at the time of delivery and the development of cerebral palsy. Among 1905 women who met inclusion criteria, the incidence of cerebral palsy in the cohort was 3.6% for women who had received magnesium sulfate and 6.4% for controls. The simulated maternal serum concentration at delivery associated with the lowest probability of delivering an infant with cerebral palsy was 4.1mg/dL (95%CI3.7 to 4.4). Our population-based estimates of magnesium disposition suggest that to optimize fetal neuroprotection and prevent cerebral palsy, magnesium sulfate administration should target a maternal serum magnesium level between 3.7 and 4.4mg/dL at delivery.

Brain derived neurotrophic factor profile in children with ischemic stroke

Objective: Assessment of brain derived neurotrophic factor (BDNF) serum levels in children who have suffered an ischemic stroke (1 month after stroke) and establishment of the correlation between BDNF serum levels and imaging and neurophysiological changes. Methods: The study included a sample of 26 children, aged between 1 and 3 months, with ischemic stroke because of perinatal hypoxic-ischemic lesions of the central nervous system (CNS); 25 children, in the same age group, were included in the control group. Enzyme-linked Immunosorbent Assay (ELISA) was used to test the serum BDNF levels. Neurophysiological and neuroimaging exams were performed. Statistical analyses were obtained by the correlation coefficient (Pearson) and ANOVA test. Results: Preliminary study results showed that compared to control group, the children who have suffered ischemic stroke, showed significantly lower serum BDNF levels (p<0.01). In the study group, low BDNF levels correlated with the degree of neuroimaging modifications (rxy=−0.72, p<0.05) and neurophysiological changes (rxy=−0.74, p<0.05). During 3 years after stroke, children with low levels of BDNF developed cerebral palsy and epilepsy. Conclusion: Children that suffered an ischemic stroke because of perinatal hypoxic-ischemic lesions of the CNS had a significantly lower serum BDNF concentrations compared to the control group. Low BDNF levels correlate with the severity of neurophysiological and neuroimaging changes and play an important role in the development of cerebral palsy and epilepsy.

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.

Cerebral Autoregulation, Brain Injury, and the Transitioning Premature Infant.

Improvements in clinical management of the preterm infant have reduced the rates of the two most common forms of brain injury, such as severe intraventricular hemorrhage and white matter injury, both of which are contributory factors in the development of cerebral palsy. Nonetheless, they remain a persistent challenge and are associated with a significant increase in the risk of adverse neurodevelopment outcomes. Repeated episodes of ischemia–reperfusion represent a common pathway for both forms of injury, arising from discordance between systemic blood flow and the innate regulation of cerebral blood flow in the germinal matrix and periventricular white matter. Nevertheless, establishing firm hemodynamic boundaries, as a part of neuroprotective strategy, has challenged researchers. Existing measures either demonstrate inconsistent relationships with injury, as in the case of mean arterial blood pressure, or are not feasible for long-term monitoring, such as cardiac output estimated by echocardiography. These challenges have led some researchers to focus on the mechanisms that control blood flow to the brain, known as cerebrovascular autoregulation. Historically, the function of the cerebrovascular autoregulatory system has been difficult to quantify; however, the evolution of bedside monitoring devices, particularly near-infrared spectroscopy, has enabled new insights into these mechanisms and how impairment of blood flow regulation may contribute to catastrophic injury. In this review, we first seek to examine how technological advancement has changed the assessment of cerebrovascular autoregulation in premature infants. Next, we explore how clinical factors, including hypotension, vasoactive medications, acute and chronic hypoxia, and ventilation, alter the hemodynamic state of the preterm infant. Additionally, we examine how developmentally linked or acquired dysfunction in cerebral autoregulation contributes to preterm brain injury. In conclusion, we address exciting new approaches to the measurement of autoregulation and discuss the feasibility of translation to the bedside.

Evaluation of motor disorders in children who were born prematurely, according to the standard electroencephalography

Aim. To determine the diagnostic value of the standard EEG patterns in disorders of motor development of born prematurely young children using logistic regression analysis.Materials and methods. An observational cohort study of 93 children development aged from birth to 36 months was carried out. All children were divided into groups - disabled children with organic lesions of the central nervous system (35.4 %), disabled children without organic lesions of the central nervous system (34.4 %), and healthy children (30.1%). Electroencephalography was performed by a standard method of background activity assessment, maturity, diffuse or local changes of brain bioelectrical activity, paroxysmal activity and the power spectrum in the range of delta, theta, alpha, beta 1 and beta 2. The study excluded the children with convulsions and anticonvulsant therapy. The corrected children age was used.Results. Disability in young children, who were born prematurely, was caused by the development of cerebral palsy. In 16.9 % of children other than motor development disorders pathology of vision, hearing and cognitive development delay was diagnosed. There were differences of delta- rhythm and alpha-rhythm in children who developed a disability at the corrected age 6–12 months. Using logistic regression analysis the odds ratio for disability in young children at the corrected age 6–12 months were determined: the part of the delta- rhythm over 28 %; low amplitude, diffuse changes; local slowdown on standard EEG.Conclusion. The authors believe that the proposed diagnostic model using noninvasive method - standard electroencephalography – helps to develop optimal steps in examining of young children and to predict motor disturbances development.

ETIOPATHOGENIC BASES FOR THE FORMATION OF CEREBRAL PALSY IN CHILDREN (REFERENCE REVIEW)

The article shows data on the effect of different factor groups on the development of cerebral palsy in children, it also describes the pathogenetic features of its formation.

Factor V Leiden Mutation as a Novel Marker in Children with Cerebral Palsy

Background: Gene mutations are known to play a role in the development of cerebral palsy (CP). The aim of this study was to determine the frequency of factor V Leiden (fVL) mutation as an etiological novel marker in Egyptian children with cerebral palsy. Methods: The study included 70 children; 50 patients with cerebral palsy (Group I) and 20 healthy subjects (Group II) matched age and sex as a control group. Venous blood samples were used for DNA extraction using PCR testing. Polymerase chain reaction (PCR) primers were designed based on exon 10 sequence of human factor V gene. Key findings: There was insignificant difference between both groups regarding comparison of demographic characteristics and risk factors except for pre-term birth (26% in study group versus 5% in control group with P = 0.04). The frequency of fVL mutation was 42% in the study group, 15% in control group with significant difference between study and control groups. There was a significant association and for the first time between homozygous fVL mutation and severe type of cerebral palsy; 60% of homozygous mutations associated with severe CP versus 9% of heterozygous mutations. Conclusions: The fVL mutation is one of the major risk factors that may increase the likelihood of cerebral thrombo-embolism and subsequent cerebral palsy in Egyptian children.

Research progress of genes of cerebral palsy

Cerebral palsy (CP) is the most common activity limitition of children, their movement and posture impairments persist throughout whole life.In recent years, CP has been significantly increasing with the improved survi-val rate of newborns.This may lead to a great burden and costs to both the family and the society.A variety of risk factors have been proposed to be associated with CP.However, recent abroad researches indicate that genetic factors may predispose to CP of newborns and initial results of related researches infer that several susceptibility genes may contri-bute to CP's development, masqueraders have a great impact on CP's clinical symptoms.Now, the recent publications related to virulence genes and masqueraders of CP are reviewed. Key words: Cerebral palsy; Virulence gene; Masquerader

Risk factors for periventricular white matter injury in very low birthweight neonates

The development of periventricular white matter injury (PWMI) in the preterm neonate is the most common insult portending neurologic impairment and is linked with the later development of cerebral palsy. The pathogenesis of PWMI targets premyelinating oligodendrocytes of the periventricular region secondary to free radicals, cytokine toxicity, and excitatory neurotransmitters. The primitive nature of the vasculature in the developing fetal cortex lends to its predilection to PWMI and cerebral ischemia with less arterial anastomoses at arterial border zones and failure to compensate for global hypotension, termed the "pressure-passive" circulation. Our objective is to determine the relative risk (RR) of fetal metabolic acidosis and perinatal infection in the development of PWMI in very low birthweight (VLBW) (<1500 g) neonates. This is a cohort study of all VLBW neonates admitted to our neonatal intensive care unit from April 2009 through December 2014, comparing those who developed PWMI on neonatal head ultrasound at 6 weeks of life to those who did not. Neonates with chromosomal or major congenital abnormalities were excluded. Generalized linear modeling, adjusting for variables significantly different on bivariate analysis, was conducted. During this 5-year and 8-month period there were 374 VLBW neonates admitted; 35 (9.4%) had PWMI. VLBW neonates without PWMI were significantly more likely to have intrauterine growth restriction (2.9% PWMI, 21.5% no PWMI; P = .006), while those neonates with PWMI had a significantly lower gestational age (26.3 ± 2.2 vs 28.0 ± 2.5 weeks; P < .001) and birthweight (868 ± 237 vs 993 ± 276 g; P = .009). There was no significant difference in umbilical arterial pH (7.25 ± 0.15 vs 7.27 ± 0.09; P = .34), base deficit (4.6 ± 6.0 vs 3.4 ± 3.3 mmol/L; P = .11), or pH <7.0 or base deficit >12 mmol/L at birth (10.7% vs 3.2%; P = .09). On bivariate analysis neonates with PWMI had a significant increase in positive cerebrospinal fluid (CSF) cultures (22.9% vs 1.5%; P < .001). The initial lumbar puncture was performed at a similar day of life, and neonates with PWMI had significantly elevated CSF white blood cell counts (5%, 50%, and 95%; 16, 175, and 709/mm(3); 1, 3, and 27/mm(3); P = .008). Generalized linear modeling, adjusted for gestational age and the presence of intrauterine growth restriction, showed that fetal metabolic acidosis had RR 2.59 (95% confidence interval, 1.14-5.92; P = .02) and neonatal CSF infection had RR 4.94 (95% confidence interval, 2.4-10.3; P < .001) for association with PWMI. The RR of neonatal CSF infection being associated with PWMI was 2-fold greater than metabolic acidosis at the time of birth. Decreasing the incidence of CSF infections would have a greater impact on preventing PWMI, a precursor of cerebral palsy.

PP06.14 – 2591: Antioxidative enzyme polymorphisms and sequelae after neonatal hypoxic-ischaemic brain injury

Objective To investigate the impact of common functional polymorphisms in antioxidative genes GPX1, SOD2 and CAT, associated with decreased capacity of defence against reactive oxygen species (ROS), in patients with epilepsy and/or cerebral palsy (CP) after perinatal hypoxic ischemic brain injury (HIBI). Hypothesis: genetically determined decreased capacity of defence against ROS may increase the risk for epilepsy and/or cerebral palsy.after perinatal hypoxic ischemic brain injury. Methods 230 consecutive patients with epilepsy and/or CP after HIBI, treated in our unite, and 95 healthy controls were included. Patients treated with therapeutic hypothermia were excluded. Patients' clinical data were collected retrospectively. Real-time PCR based methods were used to genotype GPX1 rs1050450, SOD2 rs4880 and CAT rs1001179. Statistical analysis using logistic regression was performed. Results In 214 patients with epilepsy, GPX1, SOD2 and CAT polymorphisms were not associated with the risk for epilepsy as compared to healthy controls. Similarly, the frequency distribution of GPX1, SOD2 and CAT genotypes did not differ significantly when 64 patients with epilepsy after HIBI were compared to healthy controls. Among 80 patients with HIBI, cerebral palsy was present in 51 patients. Carriers of at least one polymorphic CAT rs1001179 allele had significantly higher risk for cerebral palsy (univariable logistic regression, p=0.026; OR=3.36; 95% CI: 1.16–9.76). This difference remained significant after accounting for prematurity (multivariable logistic regression, Padj=0.011, OR=5.15, 95% CI: 1.47–18.09). No differences were observed in the distributions of GPX1 and SOD2 genotypes (p=0.816 and p=0.588). Conclusions Common GPX1, SOD2 and CAT polymorphisms influence neither the overall risk for epilepsy nor the risk for epilepsy after HIBI. CAT rs1001179 is associated with development of cerebral palsy after HIBI.

P181 – 2393: Specific features of infantile cerebral palsy development in small premature infants with extremely low birth weight and very low birth weight

Objective Study of specific features of infantile cerebral palsy development in small premature infants. Methods Complex clinical and paraclinical (neurosonography, brain MRI, encephalography – EEG) examination of psychoneurological development was performed in 312 disabled children due to infantile cerebral palsy (ICP): 98 infants with extremely low birth weight (ELBW), 109 infants with very low birth weight (VLBW), and 105 mature infants. Results ICP rate achieved in 29%, 23%, and 11% of infants with ELBW, VLBW, and mature infants correspondingly to the 2–3 years old: 7%, 5%, and 3% – as spastic tetrapalsy, or tetraparesis, 12%, 9%, and 5% – lower paraparesis, 9%, 6%, and 2% – hemiparesis, 4%, 3%, and 1% – atonic-astatic and hyperkinetic form. Severe irreversible ischemic-hemorrhagic lesions (subependymal posthemorrhagic pseudocysts, cystic encephalomalacia, progressing hydrocephalia) were visualized in MRI. Symptomatic epilepsy developed in 25% of children with ELBW, 21% – with VLBW, and 14% of mature children in 3–5 years old: 48%, 39%, and 30% – generalized forms, 52%, 61%, and 70% correspondingly – focal forms. Children suffered from resistant epilepsy forms were born mainly at 22–27 weeks of gestation. Spastic tetraparesis, hard atonic-astatic, and psychoverbal disorders were found in majority of them. Low-amplitude slow waves were registered in 98% of children with ELBW, 83% – with VLBW, and 72% of mature children at EEG; in 54%, 37%, and 25% of them correspondingly – in combination with pathologic patterns including epileptiform ones. Conclusion Perinatal cerebral pathology is evidently more frequently responsible for development of hard cerebral disorders forming the most severe forms of IPC as one of the main reasons of early persistent disability in small premature infants.

Impact of risk factors other than prematurity on periventricular leukomalacia. A population-based matched case control study

ObjectivePeriventricular leukomalacia (PVL) is a neonatal brain white matter injury associated with development of cerebral palsy, intellectual impairment, and visual disturbances. PVL is more common in premature neonates. Our objective was to examine the impact of several potential risk factors other than prematurity on the incidence of PVL. Study designA case-control study based on the Slovenian National Perinatal Information System data for the period 2002–2011. All singleton and twin pregnancies delivered at ≥22 weeks’ in Slovenia during the study period were included. Cases were pregnancies with PVL in at least one neonate. For each pregnancy in the case cohort, three pregnancies matched by gestational age and plurality were selected. Chi-square test was used to examine the associations between PVL and several potential risk factors: maternal age, pre-pregnancy body-mass-index, preexisting diabetes, gestational diabetes, pregnancy after in-vitro-fertilization, severe preeclampsia, vaginal delivery, no steroid therapy prior to delivery, small for gestational age, and fetal-inflammatory-response-syndrome. P<0.05 was considered statistically significant. ResultsOne lakh ninety one thousand and eighty three singleton and 3377 twin pregnancies delivered at ≥22 weeks’ in Slovenia during the study period. PVL was diagnosed in 86 singletons (0.045%) and 25 twins (0.74%). In all twin pregnancy cases only one twin was diagnosed with PVL. 258 singleton and 75 twin controls were matched to the 86 singleton and 25 twin cases. Of all risk factors studied, only maternal obesity and chorioamnionitis were significantly associated with PVL. ConclusionMaternal obesity and chorioamnionitis increase the risk of PVL beyond that expected solely from prematurity.

Association of a Functional Inducible Nitric Oxide Synthase Promoter Variant with Susceptibility to Infantile Cerebral Palsy

Background: Recently it has been shown an increase in the interleukin 1 beta and nitrite levels in cerebrospinal fluid as a primary response of the immature brain to oxygen deprivation in newborns that suffered perinatal asphyxia, 30% to 40% of these patients later develop neurological abnormalities incluiding cerebral palsy. Formerly was shown that an increased enzyme activity of NOS2 is responsible for the increase in nitrite levels in cerebrospinal fluid. The NOS2A gene has a polymorphic microsatellite (CCTTT)n located at -2.6 Kb from the gene promoter. The expansion of this microsatellite to 13 or 14 repeats increases transcription of the NOS2A gene and triples the nitric oxide level under hypoglycemia and hypoxia conditions. The study aim was shown that the expansion of -2.6 Kb CCTTT microsatellite in the NOS2 gene promoter, constitutes a risk factor for developing cerebral palsy in newborns that suffered perinatal asphyxia Methods: Genomic DNAs purified from peripheral leukocytes of 48 ICP patients and 57 healthy children, the (CCTTT)n microsatellite expansion were amplified by PCR, purified from agarosa gel in micro-column method and sequenced using genomelab methods development kit cycle sequencing dye terminator in an automated CEQ8000 sequencer. Results: The presence of a 14-repeat is significantly associated with infant cerebral palsy (Fisher P value=0.0122). Multivariate analysis adjusted for age and sex confirmed the association with an increased risk of developing infant cerebral palsy (odds ratio, 1.78; 95% confidence interval, 1.150-2.752; P=0.01). Conclusions: Our findings suggest that an expansion to 14 repeats of the CCTTT microsatellite plays a key role in the development of cerebral palsy in children that suffered perinatal asphyxia.

PO-0401 Il-6 Polymorphism At Position-174 In Newborn Infants With Perinatal Arterial Ischaemic Stroke: Association With Adverse Outcome

Background Inflammation has been proposed as a hallmark in the pathophysiology of stroke. A functional polymorphism in the interleukin (IL)-6 gene at position-174, encoding for the pro-inflammatory cytokine IL-6, is associated with an increased risk of neonatal brain injury or development of cerebral palsy. The aim was to study whether the IL-6-174 G/C polymorphism increased the risk of perinatal arterial ischaemic stroke (PAIS) or subsequent adverse sequelae. Methods Infants born at or above 37 weeks gestation with PAIS diagnosed by neonatal MRI (n = 63) were included. Genotyping of the IL-6-174 G/C polymorphism was performed and compared to 1008 random population controls. Perinatal variables of case infants were reviewed. Results There were no differences in IL-6-174 genotype between infants with PAIS and population controls. In a multivariable analysis, independent risk factors for adverse outcome after PAIS in a middle cerebral artery territory included CG genotype (OR 5.9; 95% CI 1.02–33.9) and male sex (OR 4.2; 95% CI 1.04–17.2). Conclusion The distribution of the IL-6-174 C >G promotor polymorphism did not differ between infants with PAIS and population controls and therefore do not seem to play a role in stroke risk. However, the IL-6-174 GC genotype was more common among infants who had an adverse outcome following PAIS in the middle cerebral artery territory, suggesting that the level of inflammation does play a role in outcome after PAIS. This may be relevant for neuroprotective strategies.

The association between sex-related interleukin-6 gene polymorphisms and the risk for cerebral palsy.

BackgroundThe relationship between genetic factors and the development of cerebral palsy (CP) has recently attracted much attention. Polymorphisms in the genes encoding proinflammatory cytokines have been shown to be associated with susceptibility to perinatal brain injury and development of CP. Interleukin-6 (IL-6) is a proinflammatory cytokine that plays a pivotal role in neonatal brain injury, but conflicting results have been reported regarding the association between IL-6 single nucleotide polymorphisms (SNPs) and CP. The purpose of this study was to analyze IL-6 gene polymorphisms and protein expression and to explore the role of IL-6 in the Chinese CP population.MethodsA total of 753 healthy controls and 713 CP patients were studied to detect the presence of five SNPs (rs1800796, rs2069837, rs2066992, rs2069840, and rs10242595) in the IL-6 locus. Of these, 77 healthy controls and 87 CP patients were selected for measurement of plasma IL-6 by Luminex assay. The SHEsis program was used to analyze the genotyping data. For all comparisons; multiple testing on each individual SNP was corrected by the SNPSpD program.ResultsThere were no differences in allele or genotype frequencies between the overall CP patients and controls among the five genetic polymorphisms. However, subgroup analysis found significant sex-related differences in allele and genotype frequencies. Differences were found between spastic CP and controls in males for rs2069837; between CP with periventricular leukomalacia and controls in males for rs1800796 and rs2066992; and between term CP and controls in males for rs2069837. Plasma IL-6 levels were higher in CP patients than in the controls, and this difference was more robust in full-term male spastic CP patients. Furthermore, the genotype has an effect on IL-6 synthesis.ConclusionsThe influence of IL-6 gene polymorphisms on IL-6 synthesis and the susceptibility to CP is related to sex and gestational age.

Timing Delivery of Vasa Previa

INTRODUCTION: The objective of this study was to determine the optimal gestational age for delivery in cases of vasa previa. METHODS: A decision-analytic model was designed to compare gestational age of delivery in vasa previa for gestational ages between 32 and 37 weeks using maternal and fetal quality-adjusted life-years in a theoretical cohort of 1,000 women with vasa previa. At each week of gestational age, we allowed for different delivery strategies: 1) premature labor with emergent delivery or 2) planned delivery by cesarean at a predetermined gestational age. Quality-adjusted life-years were calculated based on the probability of fetal bleed or no fetal bleed, with or without development of cerebral palsy, stillbirth, or uncomplicated fetal delivery. RESULTS: Delivery at 33 weeks of gestation for women with vasa previa optimizes maternal and neonatal outcomes, resulting in 6.98 stillbirths per 1,000 and 12.2 cases of cerebral palsy per 1,000. Delivery at 33 weeks of gestation maximizes total quality-adjusted life-years at 56.4. CONCLUSION: Delivery at 33 weeks of gestation for women with vasa previa optimizes maternal and fetal outcomes.

Role of Diffusion Tensor Imaging as an Independent Predictor of Cognitive and Language Development in Extremely Low-Birth-Weight Infants

Diffusion tensor imaging at term can predict later development of cerebral palsy. Less is known about its ability to independently predict cognitive and language development in extremely preterm infants. The goals of the study were to investigate the following: 1) whether regional DTI measures at term-equivalent age in extremely low-birth-weight infants (birth weight, ≤1000 g) are predictive of Bayley III developmental scores at 18- to 22-months' corrected age, and 2) to compare white matter microstructural development at term and neurodevelopmental outcomes of extremely low-birth-weight infants with healthy term controls. Fractional anisotropy and mean diffusivity in 7 vulnerable cerebral regions were measured in 42 extremely low-birth-weight and 16 term infants with high-quality DTI scans. The Bayley mental scale score (average of cognitive and language scale scores) was the primary outcome of interest with individual scores serving as secondary outcomes. Multiple linear regression modeling was used to identify the incremental ability of DTI measures to predict Bayley scores over known predictors. Compared with healthy term infants, extremely low-birth-weight infants exhibited significantly higher mean diffusivity and lower fractional anisotropy in 6 of 7 regions. At 18- to 22-months' corrected age, 39 extremely low-birth-weight infants (93%) and 14 term infants (88%) had undergone neurodevelopmental assessments. Although not statistically significant, extremely low-birth-weight infants averaged 7-9 points lower on Bayley subtests than term controls. In multivariable analyses, centrum semiovale mean diffusivity was a significant predictor of mental and language scale scores, and subventricular zone fractional anisotropy was a significant predictor of cognitive scale scores. A 10% increase in centrum semiovale mean diffusivity was associated with a 4.6 (95% CI, 1.6-7.6) point lower mental scale score (adjusted R(2) = 0.341, P = .001). In our extremely low-birth-weight cohort, DTI was an independent predictor of later cognitive and language development.

Retraction notice to “THE EFFECT OF MATERNAL INFECTION ON COGNITIVE DEVELOPMENT AND HIPPOCAMPUS NEURONAL APOPTOSIS, PROLIFERATION AND DIFFERENTIATION IN THE NEONATAL RATS” [Neuroscience 246 (2013) 422–434

Many epidemiological reports stated a strong association between maternal infection and development of cerebral palsy, which is a major cause of cognitive impairment. The pathophysiological mechanism of intrauterine inflammation is complex. Recently, it was demonstrated that inflammation has a modulating effect on adult neurogenesis. In this study, we discovered the effect of maternal infection to hippocampal neuronal apoptosis, proliferation and differentiation, and cognitive development in the developing brains of neonatal rats. Morris water maze test was used to assess learning and memory. Terminal deoxynucleotidyl transferase dUTP nick end labeling assay was used to determine neuronal apoptosis, immunostaining was conducted to assess neurogenesis, and Western blot for extracellular signal-regulated kinase (ERK), cyclic AMP responsive element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF) expression in the hippocampus. Results demonstrated that maternal infection increased neuronal apoptosis and significantly impaired spatial learning and memory ability. Maternal infection significantly increased cell proliferation, accompanied by an increased expression of ERK (P3-P7), CREB (P3-P7) and BDNF (P3). On P28, there was no significant difference of cell survival and differentiation in two groups. These results suggest that variation in ERK activity and subsequent expression of its downstream targets, including CREB and BDNF might contribute, at least partially, to modulation of inflammation related cell proliferation, survival and differentiation. Maternal infection increased hippocampal neuronal apoptosis and affected cell proliferation and differentiation in neonatal rats, which may be regarded as an etiological factor in cognitive development impairment.

Neurological impairment in a surviving twin following intrauterine fetal demise of the co-twin: A case study

It has been established that twin pregnancies are at an increased risk for complications, including the risk of morbidity or mortality for one or both of the infants. Cerebral palsy and other associated neurological deficits also occur at higher rates in twin pregnancies. This report examines two cases of intrauterine demise of one twin with subsequent survival of the co-twin. In both cases, the surviving infant suffered significant neurological sequelae. Impairments observed in these two cases include multicystic encephalomalacia and periventricular leukomalacia as well as the subsequent development of cerebral palsy. This case study explores the predisposing factors, incidence, pathophysiology, consequences, and future research implications of these findings.

165: Serum biomarker glial fibrillary acidic protein in the identification of periventricular white matter injury in preterm neonates with intraventricular hemorrhage at birth

165: Serum biomarker glial fibrillary acidic protein in the identification of periventricular white matter injury in preterm neonates with intraventricular hemorrhage at birth