Adapting Evidence-Based Practice Guidelines for Emergency Management of Seizures in Children Beyond the Neonatal Period.

BACKGROUND: The presented evidence-based clinical practice guideline (CPG) is proposed as a National CPG where we adapted the international recommendations for the emergency management of seizures in children beyond the neonatal period to suit the health care in Egypt. The quality of evidence and the strength of recommendations are indicated. This study aimed to standardize the treatment of acute epileptic seizures and to provide an easy-to-apply acute treatment protocol that will allow immediate and appropriate seizure control. METHODS: This is part of a larger program by the Egyptian Pediatric Clinical Practice Guidelines Committee (EPG) in collaboration with the staff of pediatric departments of 15 Egyptian universities and the National Research Centre. EPG was affiliated later to the Supreme Council of the Egyptian University Hospitals aiming to define the topics of, assign authors to, and assist in the adaptation of pediatric evidence-based CPGs according to a national strategic plan (http://epg.edu.eg). The committee is guided by a formal CPG adaptation methodology: the "Adapted ADAPTE." RESULTS: The Egyptian Childhood Seizure Group (ECSG) reviewed the results of the Appraisal of Guidelines for Research and Evaluation II assessment and decided to adapt the recommendations of three source CPGs: American Epilepsy Society, Italian League Against Epilepsy, Neurocritical Care Society, and Neurologic & Psychiatric Society of Zambia. Eight implementation tools were included. A comprehensive set of multifaceted CPG implementation strategies was provided for the clinicians, patients, nurses, and other relevant stakeholders contextualized to the national settings. CONCLUSIONS: Our experience with this adaptation methodology provides useful insight into its national utilization in Egypt.

Effect of educational intervention on nurses' perception and practice of antimicrobial stewardship programs.

BACKGROUND: Nurse involvement in antimicrobial stewardship programs is insufficient, which limits the programs' effectiveness. To evaluate the effect of the training programs on nurses' perception and practice of antimicrobial stewardship to embed it in practice. METHODS: A quasi-experimental study without a control group was conducted on 115 nurses. A specifically validated and designed instrument was utilized to evaluate perception and practice before, after, and 2 months follow-up the training sessions. RESULTS: The difference between the pre, post, and 2 months follow-up tests was highly significant for the dimensions of knowledge, perception, and practice (P < .01). Also, nurses reported a lack of knowledge, lack of training, high workload as barriers of AMS. Nurses suggested ways to overcome barriers such as physician and manager support, in-service training every 6 months, and saving time for training and education. CONCLUSIONS: An educational intervention improved perception and practice among nurses related to antimicrobial stewardship and easily embedded it in practice.

Pediatric Moyamoya Biomarkers: Narrowing the Knowledge Gap.

Moyamoya is a progressive cerebrovascular disorder that leads to stenosis of the arteries in the distal internal carotid, proximal middle cerebral and proximal anterior cerebral arteries of the circle of Willis. Typically a network of collaterals form to bypass the stenosis and maintain cerebral blood flow. As moyamoya progresses it affects the anterior circulation more commonly than posterior circulation, and cerebral blood flow becomes increasingly reliant on external carotid supply. Children with moyamoya are at increased risk for ischemic symptoms including stroke and transient ischemic attacks (TIA). In addition, cognitive decline may occur over time, even in the absence of clinical stroke. Standard of care for stroke prevention in children with symptomatic moyamoya is revascularization surgery. Treatment of children with asymptomatic moyamoya with revascularization surgery however remains more controversial. Therefore, biomarkers are needed to assist with not only diagnosis but also with determining ischemic risk and identifying best surgical candidates. In this review we will discuss the current knowledge as well as gaps in research in relation to pediatric moyamoya biomarkers including neurologic presentation, cognitive, neuroimaging, genetic and biologic biomarkers of disease severity and ischemic risk.

International Prevalence and Mechanisms of SARS-CoV-2 in Childhood Arterial Ischemic Stroke During the COVID-19 Pandemic.

BACKGROUND: Data from the early pandemic revealed that 0.62% of children hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had an acute arterial ischemic stroke (AIS). In a larger cohort from June 2020 to December 2020, we sought to determine whether our initial point estimate was stable as the pandemic continued and to understand radiographic and laboratory data that may clarify mechanisms of pediatric AIS in the setting of SARS-CoV-2. METHODS: We surveyed international sites with pediatric stroke expertise to determine numbers of hospitalized SARS-CoV-2 patients <18 years, numbers of incident AIS cases among children (29 days to <18 years), frequency of SARS-CoV-2 testing for children with AIS, and numbers of childhood AIS cases positive for SARS-CoV-2 June 1 to December 31, 2020. Two stroke neurologists with 1 neuroradiologist determined whether SARS-CoV-2 was the main stroke risk factor, contributory, or incidental. RESULTS: Sixty-one centers from 21 countries provided AIS data. Forty-eight centers (78.7%) provided SARS-CoV-2 hospitalization data. SARS-CoV-2 testing was performed in 335/373 acute AIS cases (89.8%) compared with 99/166 (59.6%) in March to May 2020, P<0.0001. Twenty-three of 335 AIS cases tested (6.9%) were positive for SARS-CoV-2 compared with 6/99 tested (6.1%) in March to May 2020, P=0.78. Of the 22 of 23 AIS cases with SARS-CoV-2 in whom we could collect additional data, SARS-CoV-2 was the main stroke risk factor in 6 (3 with arteritis/vasculitis, 3 with focal cerebral arteriopathy), a contributory factor in 13, and incidental in 3. Elevated inflammatory markers were common, occurring in 17 (77.3%). From centers with SARS-CoV-2 hospitalization data, of 7231 pediatric patients hospitalized with SARS-CoV-2, 23 had AIS (0.32%) compared with 6/971 (0.62%) from March to May 2020, P=0.14. CONCLUSIONS: The risk of AIS among children hospitalized with SARS-CoV-2 appeared stable compared with our earlier estimate. Among children in whom SARS-CoV-2 was considered the main stroke risk factor, inflammatory arteriopathies were the stroke mechanism.

Impact of structured simulation-based and on-job training program on nurses' competency in pediatric peripheral intravenous cannulation: Children's hospital experience.

BACKGROUND: Peripheral intravenous cannulation (PIVC) is a frequent invasive, painful procedure in children. Nursing education and competency are of great importance to decrease complications. OBJECTIVES: to evaluate the impact of structured simulation-based PIVC training and on-job assessment program on nurses' knowledge, attitudes, and performance. DESIGN: Settings/participants: A prospective, structured, competency improvement training, assessment, feedback, and reassessment conducted on 150 pediatric nurses. They provided nursing care for in-patients at the newly open Children's hospital, Ain Shams University. METHODS: PIVC insertion skills and care knowledge, structured simulation-based mannequin training arm venipuncture model and on-job assessment were conducted. In the preparatory phase, 15 nurses were interviewed to develop the assessment tools. Knowledge and attitudes were assessed quantitatively using a validated self-administered questionnaire. Structured simulation-based training, and on-job skill assessment were performed using validated observer checklist. Assessment performed at enrollment (baseline), immediate post training, and reassessment 2-months after the training, using same tools. RESULTS: Knowledge, performance, and attitudes were significantly improved for the 150 trained nurses. There was improvement in immediate post training assessment than the reassessment after 2-months, compared to baseline for total knowledge score; peripheral cannula insertion score; hand washing before aseptic procedure; skin antisepsis at puncture site; no puncture site palpation after disinfection; apply sterile dressing to puncture site, p = 0.00, respectively. There was improvement in the reassessment after 2-months than post training assessment, compared to baseline for the total attitude score, p = 0.02; peripheral cannula care, p = 0.00; aseptic technique, p = 0.00; wearing protective gloves, p = 0.01; total practice score, p = 0.00. Years of experience, last 6-months training course, practice level, educational level, age, and attitude influence overall performance. CONCLUSIONS: Structured simulation-based training and on-job skill assessment are effective for improvement of PIVC insertion and care. Continuous education, feedback, assessment/reassessment, and monitoring should be recommended to retain the gained improvement in attitudes, knowledge, and skills. Changing workplace structure and improve work environment should be studied as factors that might affect learning.

Efficacy of oral magnesium therapy in the treatment of chronic constipation in spastic cerebral palsy children: a randomized controlled trial.

BACKGROUND: Constipation is a common problem in children with spastic cerebral palsy (sCP) with a prevalence that reaches 75%. We hypothesized that treating constipation in those children will improve their health and shorten time spent in daily care. Our aim was to evaluate the efficacy and safety of oral magnesium sulfate for treating chronic constipation in children with sCP. METHODS: A prospective, double-blinded randomized control trial was carried out involving 100 children aged 2-12 years with sCP (level III-V of the Gross Motor Functional Classification system) and chronic constipation. They were followed up in the Pediatric neurology clinic, Children's hospital, Ain Shams University, May 2017- January 2019. The intervention group (O-Mg) received oral magnesium sulfate 1 mL/kg/day daily for 1 month compared to the placebo. Outcome measures were constipation improvement and decrease in bowel evacuation time after 1 month. RESULTS: Initially, weekly bowel movements, constipation scores and stool consistency were comparable in both groups. After 1 month of regular administration of oral magnesium sulfate, the constipation score, stool frequency and consistency improved compared to the placebo group (P < 0.001). Effective safe treatment was achieved in 31 (68%) and 4 (9.5%) patients in the O-Mg and placebo groups, respectively (RR, 2.95; 95% CI 2.0-4.5) (P < 0.001). Painful bowel evacuation attempts spent by mothers decreased from 25 (55.6%) of the cases initially to 10 (22%) cases after one month in the O-Mg group (P = 0.001). In contrast, in the placebo group, the decrease went from 21 (50%) cases initially to 18 (42.9%) after 1 month and was not significant (P = 0.5). CONCLUSIONS: Oral magnesium sulfate seems effective in alleviating chronic constipation and pain experience in children with sCP. Consequently, saving maternal time spent in daily bowel evacuation attempts.

Pediatric Ischemic Stroke: An Infrequent Complication of SARS-CoV-2.

OBJECTIVE: Severe complications of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) include arterial ischemic stroke (AIS) in adults and multisystem inflammatory syndrome in children. Whether stroke is a frequent complication of pediatric SARS-CoV-2 is unknown. This study aimed to determine the proportion of pediatric SARS-CoV-2 cases with ischemic stroke and the proportion of incident pediatric strokes with SARS-CoV-2 in the first 3 months of the pandemic in an international cohort. METHODS: We surveyed 61 international sites with pediatric stroke expertise. Survey questions included: numbers of hospitalized pediatric (≤ 18 years) patients with SARS-CoV-2; numbers of incident neonatal and childhood ischemic strokes; frequency of SARS-CoV-2 testing for pediatric patients with stroke; and numbers of stroke cases positive for SARS-CoV-2 from March 1 to May 31, 2020. RESULTS: Of 42 centers with SARS-CoV-2 hospitalization numbers, 8 of 971 (0.82%) pediatric patients with SARS-CoV-2 had ischemic strokes. Proportions of stroke cases positive for SARS-CoV-2 from March to May 2020 were: 1 of 108 with neonatal AIS (0.9%), 0 of 33 with neonatal cerebral sinovenous thrombosis (CSVT; 0%), 6 of 166 with childhood AIS (3.6%), and 1 of 54 with childhood CSVT (1.9%). However, only 30.5% of neonates and 60% of children with strokes were tested for SARS-CoV-2. Therefore, these proportions represent 2.9, 0, 6.1, and 3.0% of stroke cases tested for SARS-CoV-2. Seven of 8 patients with SARS-CoV-2 had additional established stroke risk factors. INTERPRETATION: As in adults, pediatric stroke is an infrequent complication of SARS-CoV-2, and SARS-CoV-2 was detected in only 4.6% of pediatric patients with ischemic stroke tested for the virus. However, < 50% of strokes were tested. To understand the role of SARS-CoV-2 in pediatric stroke better, SARS-CoV-2 testing should be considered in pediatric patients with stroke as the pandemic continues. ANN NEUROL 2021;89:657-665.

Cancer and Tumor-Associated Childhood Stroke: Results From the International Pediatric Stroke Study.

BACKGROUND: The prevalence of cancer among children with stroke is unknown. This study sought to evaluate cancer- and tumor-associated childhood ischemic stroke in a multinational pediatric stroke registry. METHODS: Children aged 29 days to less than 19 years with arterial ischemic stroke or cerebral sinovenous thrombosis enrolled in the International Pediatric Stroke Study between January 2003 and June 2019 were included. Data including stroke treatment and recurrence were compared between subjects with and without cancer using Wilcoxon rank sum and chi-square tests. RESULTS: Cancer or tumor was present in 99 of 2968 children (3.3%) with arterial ischemic stroke and 64 of 596 children (10.7%) with cerebral sinovenous thrombosis. Among children in whom cancer type was identified, 42 of 88 arterial ischemic stroke cases (48%) had brain tumors and 35 (40%) had hematologic malignancies; 45 of 58 cerebral sinovenous thrombosis cases (78%) had hematologic malignancies and eight (14%) had brain tumors. Of 54 cancer-associated arterial ischemic stroke cases with a known cause, 34 (63%) were due to arteriopathy and nine (17%) were due to cardioembolism. Of 46 cancer-associated cerebral sinovenous thrombosis cases with a known cause, 41 (89%) were related to chemotherapy-induced or other prothrombotic states. Children with cancer were less likely than children without cancer to receive antithrombotic therapy for arterial ischemic stroke (58% vs 80%, P = 0.007) and anticoagulation for cerebral sinovenous thrombosis (71% vs 87%, P = 0.046). Recurrent arterial ischemic stroke (5% vs 2%, P = 0.04) and cerebral sinovenous thrombosis (5% vs 1%, P = 0.006) were more common among children with cancer. CONCLUSIONS: Cancer is an important risk factor for incident and recurrent childhood stroke. Stroke prevention strategies for children with cancer are needed.

Treatment and outcome of childhood cerebral sinovenous thrombosis.

OBJECTIVE: To test our hypothesis that anticoagulation is associated with better neurologic outcomes in childhood cerebral sinovenous thrombosis (CSVT), we analyzed treatment and outcomes in a population of 410 children from the International Pediatric Stroke Study (IPSS). METHODS: We included patients enrolled in the IPSS registry with a diagnosis of CSVT at age >28 days with radiologic confirmation, in isolation or with concomitant arterial ischemic stroke. The primary outcome was the neurologic status at discharge. We defined unfavorable outcome as severe neurologic impairment or death at discharge. The Pediatric Stroke Outcome Measure was used for long-term outcome in those with follow-up. Predictors of anticoagulation use and outcome were analyzed by logistic regression. RESULTS: Most children (95%) had identifiable risk factors, and 82% received anticoagulation. Shift analysis demonstrated better outcomes at discharge in children who were anticoagulated, and this persisted with longer-term outcomes. In multivariable analysis, anticoagulation was significantly associated with favorable outcomes (adjusted odds ratio [aOR] unfavorable 0.32, p = 0.007) whereas infarct was associated with unfavorable outcome (aOR unfavorable 6.71, p < 0.001). The trauma/intracranial surgery was associated with a lower odds of anticoagulation use (aOR 0.14, p < 0.001). CONCLUSIONS: Within the IPSS registry, children with risk factors of trauma or intracranial surgery were less likely to receive anticoagulation for CSVT. Anticoagulation was associated with a lower odds of severe neurologic impairment or death at hospital discharge, but this finding is limited and needs further confirmation in randomized, controlled, prospective studies.

Predicting Recovery and Outcome after Pediatric Stroke: Results from the International Pediatric Stroke Study.

OBJECTIVE: To characterize predictors of recovery and outcome following pediatric arterial ischemic stroke, hypothesizing that age influences recovery after stroke. METHODS: We studied children enrolled in the International Pediatric Stroke Study between January 1, 2003 and July 31, 2014 with 2-year follow-up after arterial ischemic stroke. Outcomes were defined at discharge by clinician grading and at 2 years by the Pediatric Stroke Outcome Measure. Demographic, clinical, and radiologic outcome predictors were examined. We defined changes in outcome from discharge to 2 years as recovery (improved outcome), emerging deficit (worse outcome), or no change. RESULTS: Our population consisted of 587 patients, including 174 with neonatal stroke and 413 with childhood stroke, with recurrent stroke in 8.2% of childhood patients. Moderate to severe neurological impairment was present in 9.4% of neonates versus 48.8% of children at discharge compared to 8.0% versus 24.7% after 2 years. Predictors of poor outcome included age between 28 days and 1 year (compared to neonates, odds ratio [OR] = 3.58, p < 0.05), underlying chronic disorder (OR = 2.23, p < 0.05), and involvement of both small and large vascular territories (OR = 2.84, p < 0.05). Recovery patterns differed, with emerging deficits more common in children <1 year of age (p < 0.05). INTERPRETATION: Outcomes after pediatric stroke are generally favorable, but moderate to severe neurological impairments are still common. Age between 28 days and 1 year appears to be a particularly vulnerable period. Understanding the timing and predictors of recovery will allow us to better counsel families and target therapies to improve outcomes after pediatric stroke. ANN NEUROL 2020;87:840-852.

Arterial Ischemic Stroke Secondary to Cardiac Disease in Neonates and Children.

OBJECTIVE: We describe the risk factors for peri-procedural and spontaneous arterial ischemic stroke (AIS) in children with cardiac disease. METHODS: We identified children with cardiac causes of AIS enrolled in the International Pediatric Stroke Study registry from January 2003 to July 2014. Isolated patent foramen ovale was excluded. Peri-procedural AIS (those occurring during or within 72 hours of cardiac surgery, cardiac catheterization, or mechanical circulatory support) and spontaneous AIS that occurred outside of these time periods were compared. RESULTS: We identified 672 patients with congenital or acquired cardiac disease as the primary risk factor for AIS. Among these, 177 patients (26%) had peri-procedural AIS and 495 patients (74%) had spontaneous AIS. Among non-neonates, spontaneous AIS occurred at older ages (median 4.2 years, interquartile range 0.97 to 12.4) compared with peri-procedural AIS (median 2.4 years, interquartile range 0.35 to 6.1, P < 0.001). About a third of patients in both groups had a systemic illness at the time of AIS. Patients who had spontaneous AIS were more likely to have a preceding thrombotic event (16 % versus 9 %, P = 0.02) and to have a moderate or severe neurological deficit at discharge (67% versus 33%, P = 0.01) compared to those with peri-procedural AIS. CONCLUSIONS: Children with cardiac disease are at risk for AIS at the time of cardiac procedures but also outside of the immediate 72 hours after procedures. Many have acute systemic illness or thrombotic event preceding AIS, suggesting that inflammatory or prothrombotic conditions could act as a stroke trigger in this susceptible population.

Mortality After Pediatric Arterial Ischemic Stroke.

OBJECTIVES: Cerebrovascular disease is among the top 10 causes of death in US children, but risk factors for mortality are poorly understood. Within an international registry, we identify predictors of in-hospital mortality after pediatric arterial ischemic stroke (AIS). METHODS: Neonates (0-28 days) and children (29 days-<19 years) with AIS were enrolled from January 2003 to July 2014 in a multinational stroke registry. Death during hospitalization and cause of death were ascertained from medical records. Logistic regression was used to analyze associations between risk factors and in-hospital mortality. RESULTS: Fourteen of 915 neonates (1.5%) and 70 of 2273 children (3.1%) died during hospitalization. Of 48 cases with reported causes of death, 31 (64.6%) were stroke-related, with remaining deaths attributed to medical disease. In multivariable analysis, congenital heart disease (odds ratio [OR]: 3.88; 95% confidence interval [CI]: 1.23-12.29; P = .021), posterior plus anterior circulation stroke (OR: 5.36; 95% CI: 1.70-16.85; P = .004), and stroke presentation without seizures (OR: 3.95; 95% CI: 1.26-12.37; P = .019) were associated with in-hospital mortality for neonates. Hispanic ethnicity (OR: 3.12; 95% CI: 1.56-6.24; P = .001), congenital heart disease (OR: 3.14; 95% CI: 1.75-5.61; P < .001), and posterior plus anterior circulation stroke (OR: 2.71; 95% CI: 1.40-5.25; P = .003) were associated with in-hospital mortality for children. CONCLUSIONS: In-hospital mortality occurred in 2.6% of pediatric AIS cases. Most deaths were attributable to stroke. Risk factors for in-hospital mortality included congenital heart disease and posterior plus anterior circulation stroke. Presentation without seizures and Hispanic ethnicity were also associated with mortality for neonates and children, respectively. Awareness and study of risk factors for mortality represent opportunities to increase survival.

Human Umbilical Cord Blood CD34-Positive Cells as Predictors of the Incidence and Short-Term Outcome of Neonatal Hypoxic-Ischemic Encephalopathy: A Pilot Study.

BACKGROUND AND PURPOSE: Neonatal hypoxic-ischemic encephalopathy (HIE) is one of the leading causes of neurological handicap in developing countries. Human umbilical cord blood (hUCB) CD34-positive (CD34⁺) stem cells exhibit the potential for neural repair. We tested the hypothesis that hUCB CD34⁺ stem cells and other cell types [leukocytes and nucleated red blood cells (NRBCs)] that are up-regulated during the acute stage of perinatal asphyxia (PA) could play a role in the early prediction of the occurrence, severity, and mortality of HIE. METHODS: This case-control pilot study investigated consecutive neonates exposed to PA. The hUCB CD34⁺ cell count in mononuclear layers was assayed using a flow cytometer. Twenty full-term neonates with PA and 25 healthy neonates were enrolled in the study. RESULTS: The absolute CD34⁺ cell count (p=0.02) and the relative CD34⁺ cell count (CD34⁺%) (p<0.001) in hUCB were higher in the HIE patients (n=20) than the healthy controls. The hUCB absolute CD34⁺ cell count (p=0.04), CD34⁺% (p<0.01), and Hobel risk scores (p=0.04) were higher in patients with moderate-to-severe HIE (n=9) than in those with mild HIE (n=11). The absolute CD34⁺ cell count was strongly correlated with CD34⁺% (p<0.001), Hobel risk score (p=0.04), total leukocyte count (TLC) (p<0.001), and NRBC count (p=0.01). CD34⁺% was correlated with TLC (p=0.02). CONCLUSIONS: hUCB CD34⁺ cells can be used to predict the occurrence, severity, and mortality of neonatal HIE after PA.

Safety and Efficacy of Cerebrolysin in Infants with Communication Defects due to Severe Perinatal Brain Insult: A Randomized Controlled Clinical Trial.

BACKGROUND AND PURPOSE: The neuroregenerative drug Cerebrolysin has demonstrated efficacy in improving cognition in adults with stroke and Alzheimer's disease. The aim of this study was to determine the efficacy and safety of Cerebrolysin in the treatment of communication defects in infants with severe perinatal brain insult. METHODS: A randomized placebo-controlled clinical trial was conducted in which 158 infants (age 6-21 months) with communication defects due to severe perinatal brain insult were enrolled; 120 infants completed the study. The Cerebrolysin group (n=60) received twice-weekly Cerebrolysin injections of 0.1 mL/kg body weight for 5 weeks (total of ten injections). The placebo group (n=60) received the same amount and number of normal saline injections. RESULTS: The baseline Communication and Symbolic-Behavior-Scale-Developmental Profile scores were comparable between the two groups. After 3 months, the placebo group exhibited improvements in the social (p<0.01) and speech composite (p=0.02) scores, with 10% and 1.5% increases from baseline, respectively. The scores of the Cerebrolysin group changed from concern to no concern, with increases of 65.44%, 45.54%, 358.06%, and 96.00% from baseline in the social (p<0.001), speech (p<0.001), symbolic (p<0.001), and total (p<0.001) scores. CONCLUSIONS: Cerebrolysin dramatically improved infants' communication especially symbolic behavior which positively affected social interaction. These findings suggest that cerebrolysin may be an effective and feasible way equivalent to stem cell therapy.

Effect of caffeine on preterm infants' cerebral cortical activity: an observational study.

OBJECTIVE: Our first aim was to investigate the effects of caffeine on preterm infants' respiratory functions and brain cortical activity (conventional and amplitude-integrated electroencephalography (cEEG and aEEG)). Secondary aim was to study its long-term effects on respiratory system and electroencephalographic maturation by 36 weeks post-menstrual age. METHODS: Prospective observational study on 33 consecutively admitted preterm infants less than 34-weeks-gestation. cEEG and aEEG, cardiopulmonary and sleep state were recorded in 20 preterm infants, before, during and 2-hours after intravenous (IV) caffeine (caffeine Group), and for 13 preterms (control group). Both groups were subjected to assessment of cerebral cortical maturation by cEEG and aEEG at 36-weeks post-menstrual age as an outcome measure. RESULTS: IV caffeine administration significantly increased heart rate (p = 0.000), mean arterial blood pressure (p = 0.000), capillary oxygen saturation (p = 0.003), arousability (p = 0.000) and aEEG continuity (p = 0.002) after half an hour. No clinical seizures were recorded and non-significant difference was found in electrographic seizures activity in cEEG. At 36-weeks post-conceptional age, NICU stay was significantly longer in controls (p = 0.022). aEEG score was significantly higher in caffeine group than the control group, (p = 0.000). CONCLUSIONS: Caffeine increases preterm infants' cerebral cortical activity during infusion and results in cerebral cortical maturation at 36weeks, without increase in seizure activity.

Single dose recombinant erythropoietin versus moderate hypothermia for neonatal hypoxic ischemic encephalopathy in low resource settings.

OBJECTIVE: To determine the safety and efficacy of single dose systemic recombinant human erythropoietin (rEPO) in neonates with perinatal hypoxic Ischemic Encephalopathy (HIE), and its effect on serum brain-derived neurotrophic factor (BDNF) and neuron-specific enolase (NSE). METHODS: Forty-five full-term neonates; 30 with perinatal HIE and 15 controls were studied. HIE neonates were randomized into three intervention groups (first 6 h of life): 10 received single subcutaneous 1500 U/kg rEPO at day-1, 10 subjected to hypothermia for 72 h and 10 received supportive care. BDNF and NSE measured during first 6 h and day 5 postnatal. Daily Thompson's score, MRI brain and neuromuscular function scale for survivors at 3 months of age were done. RESULTS: Hypothermia group had best survival especially with stage-II Sarnat scale, followed by rEpo and supportive group. BDNF day-5 was significantly higher in each group compared to controls. MRI score and neuromuscular function score were non-significantly lower in the hypothermia group compared to rEPO. CONCLUSIONS: Therapeutic hypothermia was superior to single dose rEpo for neuro-protection in HIE especially in patients with stage-II Sarnat scale. Therapeutic effect of combined rEPO multiple dosing and modest hypothermia therapy should be studied.