Risk Factor For Brain Injury Research Articles

Post cardiotomy extracorporeal membrane oxygenation in pediatric patients: Results and neurodevelopmental outcomes.

The increasing complexity of congenital cardiac surgery has led to greater utilization of extracorporeal membrane oxygenation (ECMO) support for children post-surgery. This study aims to identify risk factors for mortality and brain injury in pediatric patients requiring post-cardiotomy ECMO and to evaluate their neurological outcomes. This retrospective study includes pediatric patients with congenital heart diseases who required ECMO after surgery. Risk factors for in-hospital mortality and brain injury were assessed. Neurodevelopmental status was determined using the Pediatric Cerebral Performance Category (PCPC) Scale at discharge and during follow-up. Between October 2014 and May 2021, 2651 pediatric patients underwent cardiac surgery, with 90 (3.4%) requiring ECMO. The mean age was 0.6 years, ranging from 1 day to 13 years and 7 months. ECMO was implemented for 45 patients due to CPB weaning failure (NW-CPB), 24 due to postoperative low-cardiac output syndrome (LCOS), and 21 for extracorporeal cardiopulmonary resuscitation (E-CPR). ECMO weaning was achieved in 73 patients (81%), with an overall mortality rate of 36%. Pre-implant lactate levels (OR: 1.13, 95% CI: 1.03-1.25; p = 0.009) and peak bilirubin levels (OR: 1.04, 95% CI: 0.87-1.24; p = 0.69) were risk factors for in-hospital mortality. Survival rates were 79% for LCOS, 60% for NW-CPB, and 48% for E-CPR. Brain injury incidence was 33%, with E-CPR being a significant risk factor (p = 0.006) and NW-CPB being protective (p = 0.001). Follow-up in November 2023 showed significant improvement in neurodevelopmental status (p < 0.001). Elevated pre-implant lactate and elevated bilirubin levels during ECMO are major risk factors for mortality. E-CPR is the primary risk factor for brain injury. Follow-up revealed significant improvements in neurodevelopmental outcomes.

Fetal and neonatal neuroimaging in twin-twin transfusion syndrome.

To describe the types of brain injury and subsequent neurodevelopmental outcome in fetuses and neonates from pregnancies with twin-twin transfusion syndrome (TTTS). Additionally, to determine risk factors for brain injury and to review the use of neuroimaging modalities in these cases. This was a retrospective cohort study of consecutive TTTS pregnancies treated with laser surgery in a single fetal therapy center between January 2010 and January 2020. The primary outcome was the incidence of brain injury, classified into predefined groups. Secondary outcomes included adverse outcome (perinatal mortality or neurodevelopmental impairment), risk factors for brain injury and the number of magnetic resonance imaging (MRI) scans. Cranial ultrasound was performed in all 466 TTTS pregnancies and in 685/749 (91%) liveborn neonates. MRI was performed in 3% of pregnancies and 4% of neonates. Brain injury was diagnosed in 16/935 (2%) fetuses and 37/685 (5%) neonates and all predefined injury groups were represented. Four fetal and four neonatal cases of cerebellar hemorrhage were detected. Among those with brain injury, perinatal mortality occurred in 11/16 (69%) fetuses and 8/37 (22%) neonates. Follow-up was available for 29/34 (85%) long-term survivors with brain injury and the mean age at follow-up was 46 months. Neurodevelopmental impairment was present in 9/29 (31%) survivors with brain injury. Adverse outcome occurred in 28/53 (53%) TTTS individuals with brain injury. The risk of brain injury was increased after recurrent TTTS/post-laser twin anemia-polycythemia sequence (TAPS) (odds ratio (OR), 3.095 (95% CI, 1.581-6.059); P = 0.001) and lower gestational age at birth (OR per 1-week decrease in gestational age, 1.381 (95% CI, 1.238-1.541); P < 0.001). Based on dedicated neurosonography and limited use of MRI, brain injury was diagnosed in 2% of fetuses and 5% of neonates with TTTS. Adverse outcome was seen in over half of cases with brain injury. Brain injury was related to recurrent TTTS/post-laser TAPS and a lower gestational age at birth. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Persistent pulmonary hypertension and short-term neurological outcomes in infants with moderate to severe hypoxic ischemic encephalopathy.

Our aim was to investigate the relationship between persistent pulmonary hypertension of the newborn (PPHN), short-term brain injury or death, and clinical parameters in infants with moderate to severe hypoxic ischemic encephalopathy (HIE). Retrospective single-center cohort study of 274 HIE infants, 230 underwent Therapeutic Hypothermia (TH). Primary outcome was severe HIE brain injury on MRI and/or death within the first month of life in relation to presence and severity of PPHN (clinical or echocardiographic). Secondary outcomes were HIE brain injury pattern, abnormal electroencephalogram (EEG), seizures, clinical, and laboratory differences. A logistic regression model was performed to evaluate PPHN presence and severity as risk factor for brain injury or death. The combined outcome of severe brain injury or death was higher in the clinical PPHN group vs non-PPHN (32.6 vs 22.8%, p = 0.014). There was no difference in brain injury, seizure burden or EEG abnormalities associated with PPHN, despite those with PPHN being sicker with higher ventilation needs and worse laboratory values than those without. Mortality had a strong correlation with echocardiographic PPHN with the highest incidence in severe (36%) vs moderate (7.7%) vs mild PPHN (10%, p = 0.002). Highest mortality had those with 'early exit' who did not complete 72 hours of TH (71.4%). In infants with HIE, PPHN was not associated with increased risk of brain injury as evident on MRI, nor seizure burden, despite being sicker with worse laboratory values. However, mortality rates were higher the worse the PPHN, especially with early exit from TH.

Risk factors for brain injury in premature infants with twin-to-twin transfusion syndrome: a retrospective cohort study.

Brain injury (BI) is prevalent in premature infants with twin-to-twin transfusion syndrome (TTTS), while risk factors of BI in these patients remains unknown. Our study aims to discern potential risk factors that contribute to BI in premature infants with TTTS. We conducted a retrospective cohort and analyzed clinical data of premature infants diagnosed with TTTS at the Northwest Women's and Children's Hospital between January 1, 2015 and January 1, 2020. Data included the infants' perinatal information, key postnatal examinations, laboratory tests, and treatments. Of the 84 patients enrolled in the study, 22 (26.2%) were categorized in the BI group and 62 (73.8%) in the non-BI group, based on cranial imaging. No significant differences were found at baseline between the groups in relation to the proportion of males (40.9% vs. 35.5%, P=0.845), median gestational age (weeks) [31.9 (31.5, 33.4) vs. 34.2 (31.6, 35.4), P=0.061], average weight (g) (1,676.4±567.5 vs. 1,845.2±511.7, P=0.200), maternal age (years) [29.5 (26.0, 31.0) vs. 28.5 (27.8, 31.0), P=0.656], the proportion of in-vitro fertilization (9.1% vs. 16.1%, P=0.648), cesarean sections (86.4% vs. 93.5%, P=0.549) or TTTS donor infants (50.0% vs. 51.6%, P=0.897). Multivariate logistic regression analysis indicated that invasive mechanical ventilation [invasive mechanical ventilation (IMV); odds ratio (OR) =4.365; 95% confidence interval (CI): 1.066-17.870; P=0.040], [necrotizing enterocolitis (NEC); OR =8.632; 95% CI: 1.542-48.318; P=0.014], [single intrauterine fetal demise (sIUFD); OR =14.067; 95% CI: 1.298-224.421; P=0.031], and a 5-minute Apgar score <9 (OR =4.663; 95% CI: 1.015-21.419; P=0.048) were strongly associated with BI in TTTS premature infants. Our study identifies IMV, NEC, sIUFD, and a 5-minute Apgar score <9 as independent risk factors for BI in premature infants with TTTS.

Risk factors for brain injury in patients with exertional heatstroke: A 5-year experience

PurposeMinimal data exist on brain injury in patients with exertional heatstroke (EHS) in developing country. In this study, we explored the risk factors for brain injury induced by EHS 90-day after onset. MethodsA retrospective cohort study of patients with EHS was conducted in the intensive care unit of the General Hospital of Southern Theater Command of PLA in China from April 2014 to June 2019. Patients were divided into non-brain injury (fully recovered) and brain injury groups (comprising deceased patients or those with neurological sequelae). The brain injury group was further subdivided into a death group and a sequela group for detailed analysis. General information, neurological performance and information on important organ injuries in the acute stage were recorded and analysed. Multivariable logistic regression was used to identify risk factors for brain injury after EHS and mortality risk factors for brain injury, and Kaplan-Meier survival curve was used to evaluate the effect of the neurological dysfunction on survival. ResultsOut of the 147 EHS patients, 117 were enrolled, of which 96 (82.1%) recovered, 13 (11.1%) died, and 8 (6.8%) experienced neurological sequelae. Statistically significant differences were found between non-brain injury and brain injury groups in age, hypotension, duration of consciousness disorders, time to drop core body temperature below 38.5°C, lymphocyte counts, platelet counts, procalcitonin, alanine aminotransferase, aspartate aminotransferase, creatinine, cystatin C, coagulation parameters, international normalized ratio, acute physiology and chronic health evaluation II scores, sequential organ failure assessment (SOFA) scores, and Glasgow coma scale scores (all p < 0.05). Multivariate logistic regression showed that age (OR = 1.090, 95% CI: 1.02 − 1.17, p = 0.008), time to drop core temperature (OR = 8.223, 95% CI: 2.30 − 29.40, p = 0.001), and SOFA scores (OR = 1.676, 95% CI: 1.29 − 2.18, p < 0.001) are independent risk factors for brain injury induced by EHS. The Kaplan-Meier curves suggest significantly prolonged survival (p < 0.001) in patients with early Glasgow coma scale score > 8 and duration of consciousness disorders ≤ 24 h. ConclusionsAdvanced age, delayed cooling, and higher SOFA scores significantly increase the risk of brain injury post-EHS. These findings underscore the importance of rapid cooling and early assessment of organ failure to improve outcomes in EHS patients.

PEDS6: Brain MRI Outcomes Following Carotid Reconstruction vs Ligation in Neonatal Patients Decannulated from VA-ECMO

Background: There is a paucity of data to guide carotid artery management during veno-arterial extracorporeal membrane oxygenation (VA-ECMO) decannulation. In our institution, carotid reconstruction is routinely performed by some surgeons, whereas others prefer ligation. We aimed to compare the radiographic outcomes of the different surgical techniques in our neonatal VA-ECMO survivors. Methods: We performed a single-center retrospective analysis of neonates (<28 days old) in our neonatal intensive care unit (NICU) who survived VA-ECMO decannulation between 6/2009 and 9/2022. Our institutional practice was to obtain daily screening head ultrasounds (HUS) on neonates while on ECMO and a brain MRI once clinically stable following decannulation. Patients who did not have a brain MRI following decannulation were excluded from the study. Carotid reconstruction was only performed on ECMO patients cannulated for less than 10 days, thus all patients cannulated for greater than 10 days were also excluded. The primary outcome parameter was arterial infarcts visualized on brain MRI. Secondary outcomes included extra-axial and intra-axial brain hemorrhage. Results: 82 patients met inclusion criteria for this study, including 38 (46%) that had carotid reconstruction and 44 (54%) that had carotid ligation. The two groups had similar demographics including patient characteristics, ECMO indication and duration, HUS abnormalities on ECMO and survival to hospital discharge. 21 patients (26%) had parenchymal echogenicity or intra-ventricular hemorrhage (IVH) on screening HUS while on ECMO, whereas 43 patients (52%) had either ischemic or hemorrhagic brain injury on post-ECMO MRI. There was no difference in arterial infarcts (24% vs. 27%, p=0.71) and extra-axial hemorrhage (18% vs. 21%, p=0.82) on brain MRI between the reconstructed and ligated patients. However, there was a greater number of patients with intra-axial hemorrhage with carotid reconstruction compared to ligation (45% vs. 16%, p<0.01). Conclusions: Neonates that survive VA-ECMO have multiple risk factors for brain injury. We found no difference in arterial infarcts or extra-axial brain hemorrhage following carotid reconstruction. However, there was a greater number of intra-axial hemorrhagic brain injury in patients with carotid reconstruction. Further studies are needed to discern the mechanisms underlying these radiographic differences and the effects on long-term neurocognitive outcomes.

Cerebrospinal fluid biomarkers provide evidence for kidney-brain axis involvement in cerebral malaria pathogenesis.

Cerebral malaria is one of the most severe manifestations of malaria and is a leading cause of acquired neurodisability in African children. Recent studies suggest acute kidney injury (AKI) is a risk factor for brain injury in cerebral malaria. The present study evaluates potential mechanisms of brain injury in cerebral malaria by evaluating changes in cerebrospinal fluid measures of brain injury with respect to severe malaria complications. Specifically, we attempt to delineate mechanisms of injury focusing on blood-brain-barrier integrity and acute metabolic changes that may underlie kidney-brain crosstalk in severe malaria. We evaluated 30 cerebrospinal fluid (CSF) markers of inflammation, oxidative stress, and brain injury in 168 Ugandan children aged 18 months to 12 years hospitalized with cerebral malaria. Eligible children were infected with Plasmodium falciparum and had unexplained coma. Acute kidney injury (AKI) on admission was defined using the Kidney Disease: Improving Global Outcomes criteria. We further evaluated blood-brain-barrier integrity and malaria retinopathy, and electrolyte and metabolic complications in serum. The mean age of children was 3.8 years (SD, 1.9) and 40.5% were female. The prevalence of AKI was 46.3% and multi-organ dysfunction was common with 76.2% of children having at least one organ system affected in addition to coma. AKI and elevated blood urea nitrogen, but not other measures of disease severity (severe coma, seizures, jaundice, acidosis), were associated with increases in CSF markers of impaired blood-brain-barrier function, neuronal injury (neuron-specific enolase, tau), excitatory neurotransmission (kynurenine), as well as altered nitric oxide bioavailability and oxidative stress (p < 0.05 after adjustment for multiple testing). Further evaluation of potential mechanisms suggested that AKI may mediate or be associated with CSF changes through blood-brain-barrier disruption (p = 0.0014), ischemic injury seen by indirect ophthalmoscopy (p < 0.05), altered osmolality (p = 0.0006) and through alterations in the amino acids transported into the brain. In children with cerebral malaria, there is evidence of kidney-brain injury with multiple potential pathways identified. These changes were specific to the kidney and not observed in the context of other clinical complications.

Recurrent Late-Onset Sepsis in Extremely Low Birth Weight Infants Is Associated with Motor Deficits in Early School Age

Introduction: Sepsis is regarded as a risk factor for brain injury in preterm infants. We herein hypothesize that extremely low birth weight infants (ELBWI, birth weight <1,000 g) having survived recurrent blood culture-proven late-onset sepsis (LOS) episodes are more likely to have an adverse long-term neurologic outcome. Methods: In a large multicenter observational study of ELBWI ≤28 6/7 weeks, we evaluated the impact of recurrent LOS (blood culture-proven, after day 7 of life) on development at 5–6 years. Neurodevelopment, behavior, and motor qualities were tested by blinded investigators. Univariate and logistic regression analyses were performed. Results: The cohort consisted of 1343 ELBWI including 1,080 infants without LOS, 186 infants with one LOS, and 77 with recurrent LOS, i.e., 55 infants with two and 22 infants with three LOS episodes. After Bonferroni-Holm correction, multiple logistic regression analysis revealed recurrent sepsis to be significantly associated with adverse motor development (critical MABC-2 testing: 3.3 [1.5–7.3], p = 0.003, p_B = 0.012), whereas no significant impact of recurrent LOS was found on intelligence quotient and behavioral difficulties. Odds of having critical motor testing results for infants with recurrent LOS were 1.7 times (95% confidence interval 1.4–2.3) that of infants with one LOS. Conclusion: Recurrent sepsis in preterm infants is associated with adverse long-term motor development. However, infants with recurrent infections are also more likely to have preterm-related complications, and reasons for a worse neurodevelopmental outcome remain to be elucidated.

Early screening tool for developmental delay in infancy: Quantified assessment of movement asymmetry using IR-UWB radar.

In the untact COVID-19 era, the feasibility of a noncontact, impulse-radio ultrawideband (IR-UWB) radar sensor has important medical implications. Premature birth is a major risk factor for brain injury and developmental delay; therefore, early intervention is crucial for potentially achieving better developmental outcomes. Early detection and screening tests in infancy are limited to the quantification of differences between normal and spastic movements. This study investigated the quantified asymmetry in the general movements of an infant with hydrocephalus and proposes IR-UWB radar as a novel, early screening tool for developmental delay. To support this state-of-the-art technology, data from actigraphy and video camcorder recordings were adopted simultaneously to compare relevant time series as the infant grew. The data from the three different methods were highly concordant; specifically, the ρz values comparing radar and actigraphy, which served as the reference for measuring movements, showed excellent agreement, with values of 0.66 on the left and 0.56 on the right. The total amount of movement measured by radar over time increased overall; movements were almost dominant on the left at first (75.2% of total movements), but following shunt surgery, the frequency of movement on both sides was similar (54.8% of total movements). As the hydrocephalus improved, the lateralization of movement on radar began to coincide with the clinical features. These results support the important complementary role of this radar system in predicting motor disorders very early in life.

Clinically Silent Brain Injury and Perioperative Neurological Events in Patients With Left Ventricular Assist Device: A Brain Autopsy Study.

Current studies underestimate the prevalence of brain injury in patients with left ventricular assist devices (LVADs), as CT scans are not sensitive in detecting cerebral ischemia. Using postmortem neuropathological evaluation, we sought to characterize the types and risk factors of brain injury in LVAD patients. We reviewed 24 LVAD patients who underwent brain autopsy with gross and microscopic examinations from 1993 through 2019 at a single tertiary center. Patients who expired less than 7 days after implantation or who underwent explantation more than 7 days before death were excluded. Our study demonstrated that all LVAD nonsurvivors developed brain injury. The most common brain injury was hemorrhage (71%), followed by infarct (42%) and hypoxic ischemic brain injury (HIBI) (33%), and 10 patients (42%) presented with more than 1 brain injury. Cerebral microbleeds (CMBs) and intracranial hemorrhage were present in 33% and 42%, respectively. In those with intracranial hemorrhage, subarachnoid hemorrhage (25%) and intracerebral hemorrhage (25%) were more common than subdural hematoma (4%). Intracranial hemorrhage was associated with driveline infection (P = 0.047), and HIBI was associated with prior history of chronic obstructive pulmonary disease (P = 0.037). Fourteen (60%) had clinically silent brain injury with 65% of hemorrhages and 70% of infarcts being silent. However, the impact of silent brain injury on neurologic outcome and mortality remains unclear. Standardized neurologic monitoring and surveillance are recommended to better detect these clinically silent brain injury.

Risk Factors for Brain Injury in Newborns Treated with Extracorporeal Membrane Oxygenation.

This study aimed to assess the association of clinical risk factors with severity of magnetic resonance imaging (MRI) brain injury in neonatal extracorporeal membrane oxygenation (ECMO) patients. This is a single-center retrospective study conducted at an outborn level IV neonatal intensive care unit in a free-standing academic children's hospital. Clinical and MRI data from neonates treated with ECMO between 2005 and 2015 were reviewed. MRI injury was graded by two radiologists according to a modified scoring system that assesses parenchymal injury, extra-axial hemorrhage, and cerebrospinal fluid spaces. MRI severity was classified as none (score = 0), mild/moderate (score = 1-13.5), and severe (score ≥ 14). The relationship between selected risk factors and MRI severity was assessed by Chi-square, analysis of variance, and Kruskal-Wallis tests where appropriate. Combinative predictive ability of significant risk factors was assessed by logistic regression analyses. MRI data were assessed in 81 neonates treated with ECMO. Veno-arterial (VA) patients had more severe injury compared with veno-venous patients. There was a trend toward less severe injury over time. After controlling for covariates, duration of ECMO remained significantly associated with brain injury, and the risk for severe injury was significantly increased in patients on ECMO beyond 210 hours. Risk for brain injury is increased with VA ECMO and with longer duration of ECMO. Improvements in care may be leading to decreasing incidence of brain injury in neonatal ECMO patients. · Veno-arterial ECMO is associated with more brain injury by MRI compared with veno-venous ECMO.. · Longer duration of ECMO is significantly associated with severe brain injury by MRI.. · Risk for neurologic injury may be decreasing over time with advances in neonatal ECMO..

Decreased Brain Volumes and Infants With Congenital Heart Disease Undergoing Venoarterial Extracorporeal Membrane Oxygenation.

The aims of this study were to: i) determine the spectrum of brain injury and ii) compare brain volumes between pre- and postoperative brain MRI in the infants receiving extracorporeal membrane oxygenation compared with those who did not require extracorporeal membrane oxygenation. Cohort study of infants with D-transposition of the great arteries or single ventricle physiology. Brain volume (cm) was measured using a segmentation of a volumetric T1-weighted gradient echo sequence. Brain imaging findings (intraventricular hemorrhage, white matter injuries, and stroke) were analyzed with respect to known clinical risk factors for brain injury and adverse neurodevelopmental outcomes. Clinical factors were collected by retrospective chart review. The association between brain volume and extracorporeal membrane oxygenation was evaluated using generalized estimating equations to account for repeated measures. Prospective and single-centered study. One hundred nine infants (median gestational age, 39.1 wk) with D-transposition of the great arteries (n = 77) or single ventricle physiology (n = 32) were studied pre- and postoperatively with MRI as per clinical protocol. None. Of the 28 infants (26%) receiving extracorporeal membrane oxygenation, 19 (68%) were supported with extracorporeal membrane oxygenation once, and nine (32%) were supported 2-4 times. On postoperative MRI, new white matter injury was found in only five (17%) of the extracorporeal membrane oxygenation infants versus 40 (49%) in the non-extracorporeal membrane oxygenation group (p = 0.073). The rate of stroke (9% vs 10%), intraventricular hemorrhage (24% vs 29%), and hypoxic ischemia (3% vs 14%) did not differ between the non-extracorporeal membrane oxygenation and extracorporeal membrane oxygenation groups (all p > 0.5). Accounting for D-transposition of the great arteries or single ventricle physiology diagnosis, infants requiring extracorporeal membrane oxygenation had slower brain volume with single (β = -1.67) or multiple extracorporeal membrane oxygenation runs ([β = -6.54]; overall interaction p = 0.012). Patients with d-transposition of the great arteries or single ventricle physiology undergoing extracorporeal membrane oxygenation at our center have a similar incidence of brain injury but more significant impairment of perioperative brain volumes than those not requiring extracorporeal membrane oxygenation.

Brain injury in congenital heart disease

Neurodevelopmental outcomes are quite important in patients with congenital heart disease. Studies with imaging have shown structural abnormalities that may be related to neurologic deficits. In this volume of The Journal, Claessens et al report on results comparing 2 cardiac surgery programs with different practice approaches to transition after birth, intensive care, and cardiac surgery. At both sites, MRI studies were done according to clinical protocol. The results confirm a high prevalence of brain injury at both sites. Balloon atrial septostomy, the prevalence of which was different at the 2 sites, was associated with focal brain lesions. Other risk factors for brain pathology were present and similar in both clinical populations. This report is of interest because of the findings but also because of the study design. Comparison of different practice approaches can be quite useful in determining best practices. However, it is also important to recognize that this was not a randomized clinical trial. Readers must be alert to potential bias and confounding, which could influence the results and conclusions. Article page 75▸ Brain Injury in Infants with Critical Congenital Heart Disease: Insights from Two Clinical Cohorts with Different Practice ApproachesThe Journal of PediatricsVol. 215PreviewTo determine prevalence and risk factors for brain injury in infants with critical congenital heart disease (CHD) from 2 sites with different practice approaches who were scanned clinically. Full-Text PDF

Brain Injury in Infants with Critical Congenital Heart Disease: Insights from Two Clinical Cohorts with Different Practice Approaches

To determine prevalence and risk factors for brain injury in infants with critical congenital heart disease (CHD) from 2 sites with different practice approaches who were scanned clinically. Prospective, longitudinal cohort study (2016-2017) performed at Hospital for Sick Children Toronto (HSC) and Wilhelmina Children's Hospital Utrecht (WKZ), including 124 infants with cardiac surgery ≤60days (HSC=77; WKZ=47). Magnetic resonance imaging was performed per clinical protocol, preoperatively (n=100) and postoperatively (n=120). Images were reviewed for multifocal (watershed, white matter injury) and focal ischemic injury (stroke, single white matter lesion). The prevalence of ischemic injury was 69% at HSC and 60% at WKZ (P=.20). Preoperative multifocal injury was associated with low cardiac output syndrome (OR, 4.6), which was equally present at HSC and WKZ (20% vs 28%; P=.38). Compared with WKZ, HSC had a higher prevalence of balloon-atrioseptostomy in transposition of the great arteries (83% vs 53%; P=.01) and more frequent preoperative focal injury (27% vs 6%; P=.06). Postoperatively, 30% of new multifocal injury could be attributed to postoperative low cardiac output syndrome, which was equally present at HSC and WKZ (38% vs 28%; P=.33). Postoperative focal injury was associated with intraoperative selective cerebral perfusion in CHD with arch obstruction at both sites (OR, 2.7). Compared with HSC, WKZ had more arch obstructions (62% vs 35%; P<.01) and a higher prevalence of new focal injury (36% vs 16%; P=.01). Brain injury is common in clinical cohorts of infants with critical CHD and related to practice approaches. This study confirms that the high prevalence of brain injury in critical CHD is a clinical concern and does not simply reflect the inclusion criteria of published research studies.

Glutaredoxin 2 (GRX2) deficiency exacerbates high fat diet (HFD)-induced insulin resistance, inflammation and mitochondrial dysfunction in brain injury: A mechanism involving GSK-3β

Type 2 diabetes (T2D) appears to be a significant risk factor for brain injury. Glutaredoxin 2 (GRX2) belongs to the oxidoreductase family and plays an essential role in regulating various cellular processes. However, the pathogenic role of GRX2 in high fat diet (HFD)-induced brain injury is poorly understood. In the study, the loss-of-function approach was used to explore the effects of GRX2 on brain injury in HFD-challenged mice. The results indicated that HFD treatment resulted in significant increases in the change of body weight, insulin resistance and serum lipid deposition, which were markedly exaggerated by the loss of GRX2. Moreover, HFD-caused cognitive dysfunction was further promoted in GRX2 knockout mice. Histological analysis suggested that HFD administration led to the hippocampus damage, which was potentiated by GRX2 deficiency. In addition, GRX deletion enhanced HFD-induced inflammatory response in hippocampus of mice. Furthermore, GRX2 knockout markedly enhanced HFD-triggered insulin resistance in hippocampus of mice through down-regulating the protein levels of p-insulin receptor substrate 1 (IRS1) (Y632) and p-AKT (S473). The phosphorylation of glycogen synthase kinase-3β (GSK-3β) suppressed by HFD administration was further reduced by GRX2 ablation. Moreover, HFD-induced oxidative stress and mitochondrial dysfunction were significantly aggravated in hippocampus of GRX2-knockout mice, which were largely dependent on the modulation of GSK-3β signaling. These results above demonstrated that GRX2 was responsible for HFD-induced brain injury by enhancing insulin resistance, inflammation, oxidative stress and mitochondrial impairment via the meditation of GSK-3β.

Placental Pathology and Neuroimaging Correlates in Neonates with Congenital Heart Disease

Congenital heart disease (CHD) is an independent risk factor for brain injury, including stroke, and poor neurodevelopmental outcomes, and placental abnormalities may represent an additional risk factor for brain injury in neonates. The incidence and scope of placental pathology and relationship to fetal brain abnormalities in pregnancies complicated by fetal CHD has not been explored to our knowledge. In order to determine the prevalence of placental pathology findings and whether placental findings are associated with postnatal brain injury in pregnancies complicated by fetal CHD, we reviewed placental pathology reports for 51 pregnancies complicated by CHD and scored available postnatal, pre-operative brain MRI for brain pathology. Overall, 57% of CHD infants had abnormal placental pathology. Pregnancies complicated by CHD with aortic obstruction (AO) were significantly more likely than those with no obstruction to have abnormal placental pathology (79% vs. 44%). There was a trend toward more severe brain lesions amongst patients with brain lesions and placental abnormality (55% moderate/severe) compared to those without placental abnormality (11% moderate/severe). These data suggest that placental abnormalities are common in CHD and may have a compounding effect on brain lesions in this high-risk population.

Effect of Sample Processing Delays on the Values of Serum Based Biomarkers of Brain Injury Collected from the Umbilical Cord Blood of Neonates

Background:When a neonate is born with suspected brain injury, blood samples are often obtained from the umbilical cord blood but are not always processed immediately.Objective:Test the accuracy of brain injury biomarker assays on samples that experienced delayed processing.Methods:Healthy neonates who did not have risk factors for brain injury provided cord blood samples. Group 1 blood samples were centrifuged immediately, and the serum was removed and frozen at baseline, 4, and 8 hours. Group 2 had a baseline sample processed immediately and then blood samples remained in contact with the clotted portion until 4, and 8 hours and then were centrifuged. Enzyme-linked immunosorbent assays determined the concentrations of Ubiquitin C-Terminal Hydrolase L1 (UCH-L1) and Glial Fibrillary Acidic Protein (GFAP).Results:Group 1’s average concentrations of GFAP were 62±47 pg/ml at 0 hours (n=32) with a mean increase of 3±14% and a decrease of 0.2±9% at 4 and 8 hours, respectively. UCH-L1 average concentrations were 3306±3093 pg/ml at 0 hours (n=37) with a mean increase of 3±10% at 4 hours and a mean decrease of 0.6±11% at 8 hours. Group 2’s average GFAP concentrations were 104±111 pg/ml at 0 hours (n=9) with a mean decrease of 5±9% and 7±7% at 4 and 8 hours, respectively. UCH-L1 average concentrations were 3448±2456 pg/ml at 0 hour (n=8) with a mean increase of 9±6% and 6±18% at 4 and 8 hours, respectively.Conclusion:Delays in processing up to 8 hours did not significantly affect the concentration of UCH-L1 or GFAP.

Neurological soft signs and cognitive performance in early childhood.

Neurological soft signs (NSSs), minor neurological abnormalities, have been implicated as risk factors for poor cognitive performance in small-scale studies. Here we investigate the associations between NSSs and multiple domains of cognitive performance in a large, population-based cohort and evaluate sex differences in these associations. We analyzed data from 35,710 seven-year-old children in the Collaborative Perinatal Project to study the association between the number of NSSs and cognitive test scores using multiple linear regression models adjusting for risk factors for brain injury and aberrant neurodevelopment. NSSs were associated with lower scores on all domains of cognitive performance. Each additional soft sign was associated with lower full-scale IQ (b = -4.83, 95% CI [-5.06, -4.60]), performance IQ (b = -4.28, 95% CI [-4.54, -4.02]), and verbal IQ scores (b = -4.53, 95% CI [-4.76, -4.30]), as well as arithmetic (b = -4.06, 95% CI [-4.26, -3.85]), spelling (b = -3.53, 95% CI [-3.75, -3.30]), and reading (b = -4.00, 95% CI [-4.26, -3.75]) scores on the Wide Range Achievement Test (WRAT). Only one sex difference was observed: The association between NSS and the WRAT spelling test was somewhat stronger in girls (b = -4.01, 95% CI [-4.26, -3.36]) than in boys (b = -3.53, 95% CI [-3.75, -3.30]). There is an association between NSSs and poor cognitive performance that is not attributable to established risk factors for brain injury and aberrant neurodevelopment. Further research is needed to investigate the mechanisms underlying this association and to determine if interventions targeting NSS in children might have beneficial effects on neurocognitive development. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Influencing Factors and Countermeasures of Neonatal Brain Injury

This study probes into the occurrence of neonatal brain injury, explores the influencing factors of neonatal brain injury and puts forwards relevant suggestions, with a view to providing scientific basis for clinical effective preventive measures. The study selects 225 neonates admitted to Neonatal Intensive Care Unit (NICU) from March 2016 to May 2017 in Zhengzhou Children's Hospital and collects the related clinical data and the results of cranial magnetic resonance imaging (MRI) for single factor chi-square test and binary logistic regression analysis using SPSS statistical software. The incidence rate of neonatal brain injury is 37.8%. Chorioamnionitis in pregnant women, mechanical ventilation during the neonatal period, and neonatal infection are independent risk factors for neonatal brain injury, while cesarean delivery is its protective factor (P<0.05). Risk factors for brain injury include chorioamnionitis in pregnant women, mechanical ventilation in the neonatal period, and neonatal infections, thus it is necessary to pay attention to the high-risk neonates before, during and after delivery, and take intervention measures to reduce the incidence rate of brain injury so as to improve the life quality of neonates.

Effect of nifedipine and atosiban on perinatal brain injury: secondary analysis of the APOSTEL-III trial.

Brain injury in neonates born prematurely is associated strongly with poor neurodevelopmental outcome. The aim of this study was to evaluate whether tocolysis with nifedipine or atosiban in women with threatened preterm birth can reduce the incidence of overall brain injury in neonates born prematurely. This was a secondary analysis of the APOSTEL-III trial (Dutch Clinical Trial Registry, no. NTR2947), a randomized clinical trial in which women with threatened preterm labor between 25 and 34 weeks of gestation were allocated to treatment with nifedipine or atosiban. In this secondary analysis, women delivered at ≤ 32 weeks of gestational age in the two main contributing centers were included. Primary outcome was the presence of neonatal brain injury, which was defined as presence of abnormalities on ultrasound investigation and classified into mild and severe. To evaluate type and severity of brain injury, all neonatal ultrasounds performed during neonatal intensive and medium care admission were analyzed. To test the robustness of our results, a sensitivity analysis was performed assessing differences in baseline or known risk factors for brain injury. A total of 117 neonates (from 102 women) were studied, of which 51 had been exposed to nifedipine and 66 to atosiban. Brain injury was observed in 22 (43.1%) neonates in the nifedipine group compared with 37 (56.1%) in the atosiban group (OR, 0.60; 95% CI, 0.29-1.24). Presence of mild brain injury was comparable between the nifedipine (33.3%) and atosiban (48.5%) groups (OR, 0.53; 95% CI, 0.25-1.13). Severe brain injury was also comparable between the groups, observed in 9.8% of neonates in the nifedipine vs 7.6% of those in the atosiban group (OR, 1.33; 95% CI, 0.36-4.85). Intraventricular hemorrhage (≥ Grade I) was the most frequently seen ultrasound abnormality, observed in 18 (35.3%) neonates in the nifedipine group vs 25 (37.9%) in the atosiban group (OR, 0.90; 95% CI, 0.42-1.91). The sensitivity analysis, with adjustment for maternal age and gestational age at randomization, showed no statistical difference between the groups for presence of brain injury (OR, 0.58; 95% CI, 0.27-1.27). In children born before 32 weeks of gestation after the use of tocolytics, the prevalence of brain injury was high. No significant differences were found with respect to overall brain injury between neonates exposed to nifedipine and those exposed to atosiban. However, as this study was a secondary analysis of the APOSTEL III trial, it was underpowered for brain injury. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.