Effect of Oropharyngeal Administration of Mother's Milk Prior to Gavage Feeding on Gastrin, Motilin, Secretin, and Cholecystokinin Hormones in Preterm Infants: A Pilot Crossover Study.

BACKGROUND: Oropharyngeal administration of milk prior to gavage feeding has been shown to improve feeding tolerance in preterm infants. OBJECTIVES: The aim is to study the effect of oropharyngeal administration of mother's milk (OPAMM), prior to gavage feeding, on the levels of gastrin, motilin, secretin, and cholecystokinin hormones. METHODS: Preterm infants (<32 weeks' gestation) were randomized at a corrected gestational age of 33-34 weeks, in a crossover design, to receive 1 of 2 protocols: 24 hours of OPAMM practice (applying 0.2 mL of mother's milk prior to each gavage feeding) followed by 24 hours of regular gavage-feeding practice in the first protocol or vice versa in the second protocol. The levels of gastrin, motilin, secretin, and cholecystokinin hormones were measured at the end of 24 hours of both practices. RESULTS: The data of 40 preterm infants (20 in each protocol) were analyzed. OPAMM was associated with a significant increase in the levels of motilin (median, 233; interquartile range [IQR], 196-296 vs median, 196; IQR, 128-233; P < .01), secretin (median, 401; IQR, 353-458 vs median, 370; IQR, 331-407; P = .04), and cholecystokinin (median, 21.4; IQR, 16-27.1 vs median, 14.9; IQR, 11-20.5; P <.01) but not gastrin (median, 202; IQR, 125-238 vs median, 175; IQR, 128-227; P = .7), compared with regular gavage-feeding practice. CONCLUSION: Oro-pharyngeal stimulation by OPAMM, prior to gavage feeding, significantly increased motilin hormone and possibly increased secretin and cholecystokinin hormones.

Effect of delayed cord clamping on stem cell transfusion and hematological parameters in preterm infants with placental insufficiency: a pilot randomized trial.

The feasibility of delayed cord clamping (DCC) in preterm infants with placental insufficiency (PI) is questionable. We aimed to study the effect of DCC on stem cell transfusion, hematological parameters, and clinical outcomes in preterm infants born to mothers with PI. Preterm infants, < 34 weeks' gestation, born to mothers with PI were randomized based on the timing of umbilical cord clamping into delayed clamping for 60 s (DCC group) or immediate cord clamping (ICC group) groups at time of birth. CD34 percentage as a marker of stem cell transfusion, early and late-onset anemia, hypothermia, hypotension, polycythemia, hyperbilirubinemia, duration of oxygen therapy, bronchopulmonary dysplasia, intra-ventricular hemorrhage, necrotizing enterocolitis, sepsis, mortality, and length of hospital stay were compared between studied groups. We found that peripheral blood CD34 percentage was significantly higher in DCC compared with that in the ICC group (median (IQR) of 0.5 (0.40-0.7) versus 0.35 (0.20-0.5), p = 0.004). Infants in the DCC group had significantly lower episodes of anemia of prematurity at 2 months, red blood cell transfusion, and shorter duration of oxygen therapy compared with those in the ICC group.Conclusion: In conclusion, DCC compared with ICC increased stem cell transfusion and decreased early- and late-onset anemia in preterm infants with placental insufficiency.Trial registration: NCT03731546 www.clinicaltrials.gov What is Known: • Delayed cord clamping has been recommended by the American Academy of Pediatrics as a standard of care practice during delivery of preterm infants. • The feasibility of DCC in preterm infants with placental insufficiency (PI) is uncertain. What is New: • This randomized controlled trial demonstrated that DCC in the delivery room care of preterm infants born to mothers with placental insufficiency increased stem cell transfusion and decreased early- and late-onset anemia.

Comparison of Soybean-based Oil and MCT-olive-fish-soy Oil Intravenous Lipid Emulsions on Soluble Adhesion Markers in Preterm Neonates with Sepsis: A Randomized Controlled Trial.

OBJECTIVE: To compare the effects of two different intravenous lipid emulsions on soluble adhesion markers in preterm infants with sepsis. METHODS: This randomized controlled pilot trial was conducted from February 2016 to February 2017. 40 preterm infants with sepsis were enrolled and assigned to receive either Medium chain triglyceride-Olive-Fish-Soy lipid emulsion (MOFS-LE) or soybean oil-based lipid emulsion (S-LE). Outcomes of the study were changes in sICAM-1 and leukocyte integrin b2 levels, and growth after 7 days of intervention. RESULTS: Leukocyte integrin b2 was significantly higher in MOFS-LE group. No statistically significant differences were observed for sICAM-1, duration of mechanical ventilation and antibiotics treatment, and mortality rate. CONCLUSIONS: Leukocyte integrin b2 was significantly higher in preterm septic neonates who received MOFS-LE.

Role of serum (1 3)--ß-d-glucan assay in early diagnosis of invasive fungal infections in a neonatal intensive care unit / O papel do (1 3)-ß-d-glucano no soro no diagnóstico precoce de infecções fúngicas invasivas em uma unidade de terapia intensiva neonatal

Abstract Objectives: To study the microbiological pattern of late onset neonatal sepsis cultures and to assess the diagnostic performance of serum (1,3)-β-d-glucan level for early diagnosis of invasive fungemia in high-risk infants admitted to a neonatal intensive care unit. Methods: A prospective multicenter clinical trial conducted on infants at high risk for invasive fungal infections, with suspected late onset sepsis, admitted to a neonatal intensive care unit at Mansoura University Children's Hospital and Mansoura General Hospital between March 2014 and February 2016. Results: A total of 77 newborn infants with high risk of invasive fungal infection were classified based on blood culture into three groups: no fungemia (41 neonates with proven bacterial sepsis), suspected fungemia (25 neonates with negative blood culture), and definite fungemia group (11 neonates with culture-proven Candida). The growing organisms were Klebsiella spp. (14/54); Escherichia coli (12/54); Staphylococcus spp. (12/54; coagulase-negative Staphylococcus [9/54]; Staphylococcus aureus [3/54]); Pseudomonas aerouginosa (3/54); and Proteus spp. (2/54). Moreover, 11/54 presented Candida. Serum (1,3)-β-d-glucan concentration was significantly lower in the no fungemia group when compared with the definite fungemia group. The best cut-off value of (1,3)-β-d-glucan was 99 pg/mL with sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 63.6%, 95.1%, 77.8%, 90.7%, and 88.5%, respectively. Conclusion: (1,3)-β-d-glucan assay has a limited sensitivity with excellent specificity and negative predictive value, which allow its use as an aid in exclusion of invasive neonatal fungal infection. Accurate diagnosis and therapeutic decisions should be based on combining (1,3)-β-d-glucan assay with other clinical, radiological, and microbiological findings.

Resumo Objetivos: Estudar o padrão microbiológico das culturas de sepse neonatal de início tardio e avaliar o desempenho diagnóstico do nível de (1,3)-β-D-glucano no soro para diagnóstico precoce de fungemia invasiva em neonatos de alto risco internados em uma unidade de terapia intensiva neonatal. Métodos: Ensaio clínico multicêntrico prospectivo conduzido em neonatos internados em uma unidade de terapia intensiva neonatal com suspeita de sepse de início tardio que estavam em risco de infecções fúngicas invasivas no hospital universitário infantil de Almançora e no hospital geral de Almançora entre março de 2014 e fevereiro de 2016. Resultados: Foram classificados 77 neonatos recém-nascidos com risco de infecção fúngica invasiva, com base na hemocultura, em: grupo sem fungemia, incluindo 41 neonatos com sepse bacteriana comprovada, grupo com suspeita de fungemia, incluindo 25 neonatos com hemocultura negativa; e grupo com fungemia definida, incluindo 11 neonatos com Candida comprovada por cultura. Os organismos em crescimento foram: {Klebsiella spp 14/54; E. coli 12/54; Staphylococcus spp 12/54 (Staph coagulase negativa 9/54; Staph aureus 3/54); pseudomonous aerouginosa 3/54 e Proteus spp 2/54}, além de 11/54 Candida. A concentração de (1,3)-β-D-glucano no soro foi significativamente inferior no grupo sem fungemia em comparação ao grupo com fungemia definida. O melhor valor de corte da (1,3)-β-D-glucano foi 99 pg/mL com sensibilidade, especificidade, valor preditivo positivo, valor preditivo negativo e precisão de 63,6%, 95,1%, 77,8%, 90,7% e 88,5%, respectivamente. Conclusão: O ensaio de (1,3)-β-D-glucano possui sensibilidade limitada com especificidade e valor preditivo negativo excelentes que possibilitam seu uso e ajudam na exclusão de infecção fúngica invasiva neonatal. O diagnóstico preciso e as decisões oterapêuticas devem ter como base a combinação di ensaio de (1,3)-β-D-glucano com outros achados clínicos, radiológicos e microbiológicos.

Role of serum (1,3)-ß-d-glucan assay in early diagnosis of invasive fungal infections in a neonatal intensive care unit.

OBJECTIVES: To study the microbiological pattern of late onset neonatal sepsis cultures and to assess the diagnostic performance of serum (1,3)-ß-d-glucan level for early diagnosis of invasive fungemia in high-risk infants admitted to a neonatal intensive care unit. METHODS: A prospective multicenter clinical trial conducted on infants at high risk for invasive fungal infections, with suspected late onset sepsis, admitted to a neonatal intensive care unit at Mansoura University Children's Hospital and Mansoura General Hospital between March 2014 and February 2016. RESULTS: A total of 77 newborn infants with high risk of invasive fungal infection were classified based on blood culture into three groups: no fungemia (41 neonates with proven bacterial sepsis), suspected fungemia (25 neonates with negative blood culture), and definite fungemia group (11 neonates with culture-proven Candida). The growing organisms were Klebsiella spp. (14/54); Escherichia coli (12/54); Staphylococcus spp. (12/54; coagulase-negative Staphylococcus [9/54]; Staphylococcus aureus [3/54]); Pseudomonas aerouginosa (3/54); and Proteus spp. (2/54). Moreover, 11/54 presented Candida. Serum (1,3)-ß-d-glucan concentration was significantly lower in the no fungemia group when compared with the definite fungemia group. The best cut-off value of (1,3)-ß-d-glucan was 99pg/mL with sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 63.6%, 95.1%, 77.8%, 90.7%, and 88.5%, respectively. CONCLUSION: (1,3)-ß-d-glucan assay has a limited sensitivity with excellent specificity and negative predictive value, which allow its use as an aid in exclusion of invasive neonatal fungal infection. Accurate diagnosis and therapeutic decisions should be based on combining (1,3)-ß-d-glucan assay with other clinical, radiological, and microbiological findings.

Conventional Versus Prolonged Infusion of Meropenem in Neonates With Gram-negative Late-onset Sepsis: A Randomized Controlled Trial.

BACKGROUND: Gram-negative bacteria are associated with significant morbidity and mortality in preterm and term newborns. Meropenem has widespread efficacy and often allows for monotherapy in this group. Prolonged infusion instead of infusion over 30 minutes has been suggested to result in higher microbiologic efficacy. OBJECTIVE: To compare the clinical and microbiologic efficacy and safety of prolonged infusions versus conventional dosing of meropenem in neonates with Gram-negative late-onset sepsis (GN-LOS). METHODS: A prospective, randomized clinical trial was conducted in neonates with GN-LOS admitted to neonatal intensive care unit (NICU), Mansoura University Children's Hospital, between August 2013 and June 2015. Patients were randomly assigned to receive either intravenous infusion of meropenem over 4 hours (infusion group) or 30 minutes (conventional group) at a dosing regimen of 20 mg/kg/dose every 8 hours and 40 mg/kg/dose every 8 hours in meningitis and Pseudomonas infection. Clinical and microbiologic success in eradication of infection were the primary outcomes. Neonatal mortality, meropenem-related (MR) duration of mechanical ventilation, MR length of NICU stay, total length of NICU stay, duration of respiratory support (RS), duration of mechanical ventilation, MR duration of inotropes and adverse effects were secondary outcomes. RESULTS: A total of 102 infants (51 in each group) were recruited. The infusion group demonstrated a significantly higher rate of clinical improvement and microbiologic eradication 7 days after starting meropenem therapy compared with the conventional group. Mortality and duration of RS were significantly less in the infusion group compared with conventional group. Acute kidney injury after meropenem treatment was significantly less in the infusion group compared with the conventional group. CONCLUSIONS: Prolonged infusion of meropenem in neonates with GN-LOS is associated with higher clinical improvement, microbiologic eradication, less neonatal mortality, shorter duration of RS and less acute kidney injury compared with the conventional strategy.

Pentoxifylline therapy for late-onset sepsis in preterm infants: a randomized controlled trial.

BACKGROUND: The role of pentoxifylline (PTX) in reducing mortality associated with neonatal sepsis is not well established. We aimed to assess the efficacy and safety of PTX as an adjunct to antibiotics on mortality and morbidity in preterm infants with late-onset sepsis (LOS). METHODS: Double blind, randomized controlled trial was conducted on 120 preterm infants with LOS. They were randomly assigned to receive either intravenous PTX 5 mg/kg/hr for 6 hours on 6 successive days or placebo. Death before hospital discharge was our primary outcome and secondary outcomes were length of hospital stay, duration of respiratory support, duration of antibiotics use, short-term morbidity of preterm infants, tumor necrosis factor-alpha concentrations, C-reactive protein concentrations, and adverse effects of PTX. RESULTS: A total of 120 infants were enrolled, 60 in each group, 78 (65%) infants had confirmed and 42 (35%) had suspected LOS. There were no significant differences between groups regarding mortality [6 (10%) in PTX vs. 10 (16.5%) in placebo, P = 0.44], short-term morbidity and combined mortality and/or short-term morbidity [18 (30%) vs. 24 (40%), P = 0.23]. PTX therapy was associated with significant reduction of serum tumor necrosis factor-alpha and C-reactive protein concentrations. The length of hospital stay, durations of respiratory support and antibiotic therapy were significantly shorter in the PTX group. Patients in PTX group had less need for vasopressors, lower incidence of metabolic acidosis, disseminated intravascular coagulopathy and thrombocytopenia. No adverse effects to PTX were reported. CONCLUSIONS: PTX has a beneficial adjuvant effect to antibiotic therapy in preterm infants with LOS without significant impact on neonatal mortality and morbidity.

Weaning preterm infants from continuous positive airway pressure: evidence for best practice.

BACKGROUND: Nasal continuous positive airway pressure (NCPAP) is frequently used in preterm infants. However, there is no consensus on when and how to wean them from NCPAP. DATA SOURCES: Based on recent publications, we have reviewed the criteria of readiness-to-wean and factors affecting weaning success. A special focus is placed on the methods of weaning from NCPAP in preterm infants. RESULTS: Practical points of when and how to wean from NCPAP in preterm infants are explained. Preterm infants are ready to be weaned from NCPAP when they are stable on a low NCPAP pressure with no (or minimal) oxygen requirement. Methods used to wean from NCPAP include: sudden weaning of NCPAP, gradual decrease of NCPAP pressure, graded-timeoff NCPAP (cycling), weaning to high or low flow nasal cannula, and a combination of these methods. The best strategy for weaning is yet to be determined. Cyclingoff NCPAP increases the duration of NCPAP and length of hospital stay without beneficial effect on success of weaning. Gradual decrease of NCPAP pressure is more physiological and better tolerated than cycling-off NCPAP. CONCLUSION: Further studies are needed to reach a consensus regarding the optimal timing and the best method for weaning from NCPAP in preterm infants.

High versus low-dose caffeine for apnea of prematurity: a randomized controlled trial.

UNLABELLED: The optimum caffeine dose in preterm infants has not been well investigated. We aimed to compare the efficacy and safety of high versus low-dose caffeine citrate on apnea of prematurity (AOP) and successful extubation of preterm infants from mechanical ventilation. We compared high-dose (loading 40 mg/kg/day and maintenance of 20 mg/kg/day) versus low-dose (loading 20 mg/kg/day and maintenance of 10 mg/kg/day) caffeine citrate in preterm infants <32 weeks gestation, presented with AOP within the first 10 days of life. A total of 120 neonates (60 in each group) were enrolled. High-dose caffeine was associated with a significant reduction in extubation failure in mechanically ventilated preterm infants (p<0.05), the frequency of apnea (p<0.001), and days of documented apnea (p<0.001). High-dose caffeine was associated with significant increase in episodes of tachycardia (p<0.05) without a significant impact on physician decision to withhold caffeine. CONCLUSION: The use of higher, than current standard, dose of caffeine may decrease the chance of extubation failure in mechanically ventilated preterm infants and frequency of AOP without significant side effects. WHAT IS KNOWN: • Caffeine therapy for treatment of apnea of prematurity has been well established over the past few years. The optimal loading and maintenance dose of caffeine in preterm infants is not well-studied. What is New: • This double blind randomized controlled trial demonstrated that using a higher, than current standard, loading and maintenance doses of caffeine for treatment of apnea in preterm infants is well tolerated and significantly decrease the frequency of apnea.

Aflatoxin B1 level in relation to child's feeding and growth.

OBJECTIVE: To study the influence of sociological factors, breast feeding and weaning on aflatoxin exposure in children as well as to determine the effect of aflatoxin exposure on child's growth. METHODS: A questionnaire, administered to the mothers of forty-six children, obtained information on the child's age, sex, residence, feeding, weaning and general health status. Maternal parity, education and occupation were also collected. Height for age Z-score (HAZ) and weight for age Z-score (WAZ) of children were calculated at the time of recruitment. TLC analysis was performed for aflatoxin B1 level in studied children and their mothers. RESULTS: Aflatoxin B1 was detected in 17 out of 46 (36.96%) of children's serum at a median concentration of 51.61 (30.565-62.795) ppm and in 17 out of 46 (36.96%) of mother's serum at a median concentration of 50 (35.59-84.93) ppm. Aflatoxin B1 level was neither affected by child's age, sex, residence whether rural or urban, maternal age, parity, education nor occupation. Aflatoxin B1 in breastfed patients was significantly lower than in non-breastfed ones (p = 0.034). Weight for age Z-score (WAZ) showed no significant difference between aflatoxin B1 negative and positive cases (p = 0.422) while height for age Z-score (HAZ) was significantly lower in aflatoxin B1 positive compared to negative cases (p = 0.001). A significant positive correlation between aflatoxin B1 in the present cases and their mothers (r = 0.881, p = 0.0001) and a significant negative correlation between aflatoxin B1 in present cases and their height-z-score (HAZ) (r = -0.460, p = 0.001) was detected. CONCLUSIONS: Breast feeding results in lower aflatoxin exposure. Also, a strong association between aflatoxin exposure and impaired child's growth exists.

Dose of intravenous lipids and rate of bacterial clearance in preterm infants with blood stream infections.

BACKGROUND: Intravenous lipid emulsion (IVLE) is an integral part of the total parenteral nutrition (TPN) regimen in neonates. The use of IVLE during sepsis is the subject of controversy because it may interfere with phagocytosis of microbes by macrophages and may lead to significant hypertriglyceridemia. OBJECTIVE: This paper aims to study the rate of clearance of bacteria in relation to dose of IVLE administered to preterm infants with blood stream infections (BSIs). METHODS: Preterm infants (mean gestational age ± SD, 32.0 ± 2.5 weeks) with culture-proven BSI and receiving TPN were randomized to two groups. The first group (n = 22) was given the usual dose of IVLE according to a standard protocol (starting from 0.5 g kg(-1) day(-1) and gradually increased by 1 g kg(-1) day(-1) to a maximum of 3.5 g kg(-1) day(-1)); in the second group (n = 20), IVLE were restricted at a dose of 1 g kg(-1) day(-1). Samples for blood cultures were withdrawn every 24 h until a negative culture was obtained. CRP was measured daily until its normalization. Serum triglycerides were monitored daily. RESULTS: The rate of bacterial clearance was significantly more rapid in the restricted-dose IVLE group compared to the standard-dose group [72 (48-120) versus 144 (72-168) h, p = 0.001]. Daily weight increment was significantly greater in the standard-dose IVLE group compared to the restricted-dose IVLE group [25 (6.9-31.9) versus 0.9 (-3.3-11.7) g, p = 0.0001]. The duration of antibiotic use was significantly reduced in the restricted-dose IVLE group compared with the standard-dose IVLE group (10.0 ± 4.5 vs 14.9 ± 5.1 days; p = 0.003). The durations of TPN, mechanical ventilation, and hospitalization were not significantly different between groups. CONCLUSIONS: Restriction of the dose of IVLE to 1 g kg(-1) day(-1) in preterm infants with BSI is associated with earlier negative blood cultures and reduced duration of antibiotic therapy but was associated with a lower daily weight increments.

Early weaning from CPAP to high flow nasal cannula in preterm infants is associated with prolonged oxygen requirement: a randomized controlled trial.

OBJECTIVE: To determine the better approach for weaning preterm infants from nasal continuous positive airway pressure (NCPAP) with or without transitioning to nasal cannula (NC). DESIGN/METHODS: This is a randomized, open label, controlled trial. Preterm infants born at ≥28 weeks gestation who were clinically stable on NCPAP of 5 cm H(2)O with FiO(2)<0.30 for at least 24 h were randomly assigned to one of 2 groups. The no-NC group were kept on NCPAP until they were on FiO(2)=0.21 for 24 h, and then were weaned off NCPAP completely without any exposure to NC. If they met failing criteria, NCPAP was re-instituted. The NC-group was weaned off NCPAP when FiO(2) was ≤0.30 to NC (2 L/min) followed by gradual weaning from oxygen. Infants who failed NC were supported back with NCPAP for 24 h before making a second attempt of NC. RESULTS: Sixty neonates were enrolled; 30 in each group. The two groups were similar in birthweight, gestational age, sex, antenatal steroids, mode of delivery, use of surfactant and xanthines, and duration of mechanical ventilation. After randomization, the no-NC group had fewer days on oxygen [median (interquartile range): 5 (1-8) vs 14 (7.5-19.25) days, p<0.001] and shorter duration of respiratory support [10.5 (4-21) vs 18 (11.5-29) days, p=0.03]. There were no differences between groups regarding success of weaning from NCPAP. CONCLUSIONS: Weaning preterm infants from NCPAP to NC is associated with increased exposure to oxygen and longer duration of respiratory support.

Anasarca: not a nephrotic syndrome but dermatomyositis.

Juvenile dermatomyositis (JDM) is a rare autoimmune disease characterized by inflammation of the muscle, connective tissue, skin, gastrointestinal tract, and small nerves. Periorbital and facial edema may also be associated. Although localized edema is a common feature of JDM, generalized edema has rarely been reported. Here, we report a 3.5-year-old boy with JDM presenting with generalized edema. The diagnostic criteria of JDM rely on typical clinical manifestations that include: severe symmetric weakness of the proximal musculature, characteristic cutaneous changes, elevated serum skeletal muscle enzymes, and myopathic electromyographic pattern. Our patient initially received methylprednisolone and intravenous immunoglobulin (IVIG) without significant improvement, so he was given azathioprine and a prolonged course of oral prednisolone. We conclude that JDM should be suspected in patients presenting with anasarca in the absence of laboratory parameters of other causes of generalized edema and an appearance of heliotrope rash with muscle weakness. Also, we suggest that muscle magnetic resonance imaging (MRI) should be considered among the diagnostic tools of JDM.

Endocannabinoids potently protect the newborn brain against AMPA-kainate receptor-mediated excitotoxic damage.

Brain lesions induced in newborn mice or rats by the glutamatergic agonists ibotenate (acting on NMDA and metabotropic receptors) or S-bromowillardiine (acting on AMPA-kainate receptors) mimic some aspects of white matter cysts and transcortical necrosis observed in human perinatal brain damage associated with cerebral palsy. Exogenous and endogenous cannabinoids have received increasing attention as potential neuroprotective agents in a number of neurodegenerative disorders of the adult. One recent study showed neuroprotection by the cannabinoid agonist WIN-55212 in a newborn rat model of acute severe asphyxia. The present study was designed to assess the neuroprotective effects of the endogenous cannabinoid anandamide using a well-defined rodent model of neonatal excitotoxic brain lesions. In this model, anandamide provided dose-dependent and long-lasting protection of developing white matter and cortical plate reducing the size of lesions induced by S-bromowillardiine. Anandamide had only marginal neuroprotective effect against ibotenate-induced cortical grey matter lesions. Anandamide-induced neuroprotection against AMPA-kainate receptor-mediated brain lesions were blocked by a CB1 antagonist but not by a CB2 antagonist. Furthermore, anandamide effects were mimicked by a CB1 agonist but not by a CB2 agonist. Real-time PCR confirmed the expression of CB1 receptors, but not CB2 receptors, in the untreated newborn neocortex. Finally, neuroprotective effects of anandamide in white matter involved increased survival of preoligodendrocytes and better preservation of myelination. The present study provides experimental support for the role of endocannabinoids as a candidate therapy for excitotoxic perinatal brain lesions.

Excitatory amino acids and magnesium sulfate in neonatal asphyxia.

OBJECTIVE: The excitatory amino acids (EAA); glutamate and aspartate are released into the cerebrospinal fluids (CSF) of asphyxiated newborns. The objectives of this study were: (a) to examine the relation of the concentration of EAA in the CSF with the degree of brain injury, (b) To determine the time of the release of these EAA into the CSF, and (c) to detect the effect of magnesium sulfate (MgSO(4)) on their levels. DESIGNS AND METHODS. A randomized controlled trial was conducted on 47 full term asphyxiated newborns. Twenty three infants received an intravenous 10% solution of MgSO(4) at a dose of 250 mg/kg within the first 24h of life while the other 24 newborns received isotonic saline (0.9%) of an equal volume. Levels of glutamate and aspartate were measured before and 72 h after giving the trial solution. Results. In the study population (n=47) both glutamate and aspartate were significantly elevated in infants with higher grades of HIE compared to those with lower grades (P=0.013 and 0.031, respectively). Compared to baseline level, glutamate decreased significantly over time in placebo group (-8.28+/-14.26, P=0.025) and in MgSO(4) group (-14.39+/-18.72, P=0.005). Glutamate concentration did not differ between groups when measured at baseline (29.26+/-16.31 vs. 31.27+/-22.62, P=0.82) and at 72 h (19.28+/-15.63 vs. 19.6+/-16.54, P=0.87). The change in aspartate concentration over time was not significant in placebo group (-0.45+/-1.96, P=0.34) or in MgSO(4) group (-0.7+/-3.19, P=0.37). Aspartate did not differ between groups when measured at baseline (3.52+/-2.4 vs. 3.92+/-2.59, P=0.49) or at 72 h (2.79+/-1.24 vs. 3.05+/-2.48, P=0.92). Conclusions. The EAA; glutamate and aspartate are released in the CSF of asphyxiated newborns immediately after birth and declined by 72 h. Their initial concentrations correlated with the severity of HIE. Postnatal administration of MgSO(4) did not alter the levels of these 2 EAA.