Sahar M. A. Hassanein

Melatonin and Sleep-Related Problems in Children With Intractable Epilepsy

Children with epilepsy have high rates of sleep problems. Melatonin has been advocated in treatment of sleep disorders, and its beneficial effect has been confirmed in insomnia. The aim of this study was to assess melatonin levels in children with intractable epilepsy and its relation to pattern of sleep and characteristics of seizure disorder, as well as the effect of melatonin therapy on those parameters. The study was conducted on 23 children with intractable epilepsy and 14 children with controlled seizures. Patients were evaluated by psychometric sleep assessment and assay of diurnal and nocturnal melatonin levels. Children with intractable epilepsy received oral melatonin before bedtime. They were reassessed after 3 months. Children with intractable epilepsy had higher scores for each category of sleep walking, forcible teeth grinding, and sleep apnea. At the end of therapeutic trial, patients with intractable epilepsy exhibited significant improvement in bedtime resistance, sleep duration, sleep latency, frequent nocturnal arousals, sleep walking, excessive daytime sleepiness, nocturnal enuresis, forcible teeth grinding, sleep apnea, and Epworth sleepiness scores. There was also significant reduction in seizure severity. Thus, use of melatonin in patients with intractable seizures was associated with improvement of both many sleep-related phenomena and the severity of seizures.

Vascular endothelial growth factor in neonates with perinatal asphyxia.

BACKGROUND Vascular endothelial growth factor (VEGF) is a polypeptide growth factor that is activated by tissue hypoxia. The role of VEGF in perinatal asphyxia in human neonates is yet to be clarified. In infants who develop moderate to severe acute hypoxic ischemic encephalopathy (HIE) it is crucial to clearly understand physiologic and biochemical changes that accompany HIE before a novel treatment can be developed. OBJECTIVES To assess VEGF in cord blood of infants suffering from perinatal asphyxia, and to determine whether an association exists between increased concentrations of VEGF and the risk for development of encephalopathy. STUDY DESIGN We prospectively studied 40 full term infants; of them 20 infants suffered from perinatal asphyxia, and 20 control infants of comparable age and sex. We obtained cord blood samples from all subjects immediately after delivery. Neurological examination and grading of HIE were performed during the first day of life. RESULTS Birth weight, gestational age and gender did not differ between the control (n=20) and asphyxia (n=20) groups. Within the asphyxia group four infants developed HIE; one with severe encephalopathy who died shortly after birth, while the other three infants had moderate HIE. Concentrations of VEGF were increased in infants with asphyxia when compared to controls (P0.001). Within the asphyxia group, infants with HIE had significantly increased concentrations of VEGF when compared to non-HIE asphyxiated infants (P=0.008). In the logistic regression model, VEGF inversely correlated with pH and PO(2) in cord blood, and Apgar scores at 1min, while it did not associate with gestational age and birth weight. CONCLUSIONS This study indicates that VEGF is increased in cord blood of neonates following birth asphyxia, and that VEGF is specifically most increased in infants who later developed encephalopathy. Further studies are required to determine the role of VEGF in brain insult. Such studies will help determine whether a therapeutic role for VEGF or VEGF inhibitors can exist for HIE infants.

Neonatal nursery noise: practice-based learning and improvement.

Objectives: To study the impact of interrupted loud noise in Neonatal Intensive Care Unit (NICU) on neonatal physiologic parameters, and apply methods to alleviate noise sources through teaching NICU’s staff. Methods: Noise level measured at different day times and during different noisy events in the NICU. Changes in the heart rate, respiratory rate and oxygen saturation were recorded just before and immediately after providing noisy events for 36 preterm and 26 full-term neonates. Focused training, guided by sound-level-meter, was provided to the NICU’s staff to minimize noise. Results: The highest mean baseline noise level, 60.5 decibel (dB), was recorded in the NICU critical care area at 12:00 am. The lowest level, 55.2 dB was recorded at 10:00 pm. Noise level inside the incubators was significantly lower than outside, p < 0.001. Noisy events resulted in a significant increase in heart and respiratory rates in preterm neonates as compared to full-terms, p < 0.05. Conclusion: Noise in our NICU exceeded the international permissible levels. Noisy events are numerous, which altered the neonates’ physiologic stability especially preterm infants. Staff education is mandatory in ameliorating noise pollution with its deleterious effects on neonatal physiologic homeostasis.

Gestational Age, Sex and Maternal Parity Correlate with Bone Turnover in Premature Infants

Factors affecting bone turnover in premature infants are not entirely clear but certainly are different from those influencing bones of adults and children.To identify fetal and maternal factors that might influence bone turnover, we prospectively studied 50 infants (30 preterm and 20 full-term) born at Ain Shams University Obstetric Hospital in Cairo, Egypt. Maternal parity and medical history and infants weight, gestational age, gender and anthropometrical measurements were recorded. Cord blood samples were collected and serum type I collagen C-terminal propeptide (PICP) was assessed as a marker for fetal bone formation. First morning urine samples were collected and pyridinoline cross-links of collagen (Pyd) were measured as an index for bone resorption. Serum PICP was higher in premature infants when compared with full-term infants (73.30 ± 15.1 versus 64.3 ± 14.7, p = 0.022) and was higher in male premature infants when compared with females (81.64 ± 9.06 versus 66.0 ± 15.7, p = 0.018). In a multiple regression model using PICP as the dependent variable and controlling for different infant and maternal conditions, PICP significantly correlated with infant gender (r = 8.26 ± 4.1, p = 0.05) maternal parity (r = −2.106 ± 0.99, p = 0.041) and diabetes (r = 22.488 ± 8.73, p = 0.041). Urine Pyd tended to increase in premature infants (612 ± 308 versus 434 ± 146, p = 0.057) and correlated significantly with gestational age (r = −63.93 ± 19.55, p = 0.002). Therefore, bone formation (PICP) is influenced by fetal age and gender, as well as maternal parity and diabetes. Bone resorption (Pyd) is mostly dependent on gestational age only. Further in-depth studies are needed to enrich management of this vulnerable population.

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

Abstract 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 Thompsons 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.

Cord blood interleukin-6 and neonatal morbidities among preterm infants with PCR-positive Ureaplasma urealyticum.

Objectives: To evaluate the clinical significance of Ureaplasma urealyticum recovery from umbilical cord blood, using Polymerase Chain Reaction (PCR), and its association with umbilical cord interleukin-6 (IL-6) levels and neonatal morbidity in preterm infants. Methods: Cord blood PCR for Ureaplasma urealyticum, and IL-6 were assessed in relation to neonatal outcomes of 30 preterm deliveries of less than 35 weeks’ gestation. Results: Ureaplasma urealyticum was present in 43.3% of the examined cord blood samples. Positive neonatal Ureaplasma urealyticum was more common in association with premature rupture of membranes, chorioamnionitis, antenatal maternal use of antibiotics, and earlier gestation. Ureaplasma urealyticum was also associated with an early pro-inflammatory immune response (i.e. elevated IL-6 and positive C-reactive protein). Cutoff level of interleukin-6 of 240 pg% predicts the occurrence of respiratory distress syndrome (RDS), in neonates with positive PCR for Ureaplasma urealyticum. Conclusions: Preterm patients with positive cord blood PCR for Ureaplasma urealyticum were more likely to have premature rupture of membrane, antenatal antibiotics, chorioamnionitis, earlier gestation, pro-inflammatory response, and RDS than those with a negative PCR. High IL-6 is more likely associated with RDS in Ureaplasma urealyticum positive neonates.

Predictive value of vascular endothelial growth factor in preterm neonates with intraventricular haemorrhage

Objective: Intraventricular haemorrhage (IVH) is a major problem in premature infants. Our objective is to assess the early predictive value of vascular endothelial growth factor (VEGF) for development of IVH and management of its squeal in preterm neonates. Methods: We prospectively studied 150 preterm neonates (PT) less than 34 weeks gestation. Fifty of them completed the study. 30/50 developed IVH during follow up, and 20 did not. First 24 hours, and 3rd day serum samples were collected. Cerebrospinal fluid (CSF) samples were withdrawn for 10 IVH patients. Results: Serum VEGF; both samples were increased in IVH compared to non-IVH group (P = 0.001). PHVD-group (n = 10) had higher VEGF in both samples than resolved IVH (P = 0.004), (P = 0.005). While, VEGF increased in the IVH group 2nd sample compared to 1st (P = 0.000), it decreased in non-IVH group, P = 0.033). Each 1 unit increase in 1ST VEGF increased the risk of occurrence of IVH by 1.6%. 3rd day VEGF at a cut-off value of 135 pg/ml is 96% sensitive and 100% specific to predict PHVD. Serum VEGF inversely correlated with TLC, pH, PO2 and HCO3, and positively correlated with PCo2 and FiO2. Conclusion: Serum VEGF predicts development of IVH and PHVD in PT neonates. Also, high CSF level of VEGF could predict the need for permanent shunt placement.

Umbilical cord blood CD45+/CD34+ cells coexpression in preterm and full-term neonates: a pilot study

Objective. Human umbilical cord blood (hUCB) is rich in stem cells. The CD45+/CD34+ coexpression in hUCB is a marker of hemopoietic progenitor cells. The objective of this study is to compare the coexpression of hUCB CD45+/CD34+ cells in preterm (PT) and full-term (FT) neonates. Methods. We studied the coexpression of hUCB CD45+/CD34+ cells in PT and FT neonates. The study included 25 PT (29–36 weeks gestation) and 25 FT (37–41) neonates delivered at Ain Shams University, Maternity Hospital. Absolute mononuclear layer cord blood CD45+/CD34+ cell count were measured by flow cytometry. Morbidity was assessed for 12 of the studied 25 PT infants, using Morbidity Assessment Index for Newborns score. Results. The absolute CD45+/CD34+ count did not differ between PT and FT infants: Z = −0.485, p = 0.63. There was no correlation between absolute cell count and GA (r = 0.013, p = 0.9) for all 50 neonates. Mode of delivery did not affect the absolute count in the PT infants: Z = –0.6, p = 0.57. There was no correlation between the degree of morbidity and absolute cell count in PT neonates; r = 0.13, p = 0.69. Conclusion. The absolute cell count is not affected by gestational age and did not relate to morbidity scores in the studied PT infants. Further, wide-scale work will be needed to study CD45+/CD34+ count in hUCB in sick PT neonates.

Two-stage single-volume exchange transfusion in severe hemolytic disease of the newborn

Objective: Evaluation of two-stage single-volume exchange transfusion (TSSV-ET) in decreasing the post-exchange rebound increase in serum bilirubin level, with subsequent reduction of the need for repeated exchange transfusions. Methods: The study included 104 neonates with hyperbilirubinemia needing exchange transfusion. They were randomly enrolled into two equal groups, each group comprised 52 neonates. TSSV-ET was performed for the 52 neonates and the traditional single-stage double-volume exchange transfusion (SSDV-ET) was performed to 52 neonates. Results: TSSV-ET significantly lowered rebound serum bilirubin level (12.7 ± 1.1 mg/dL), compared to SSDV-ET (17.3 ± 1.7 mg/dL), p < 0.001. Need for repeated exchange transfusions was significantly lower in TSSV-ET group (13.5%), compared to 32.7% in SSDV-ET group, p < 0.05. No significant difference was found between the two groups as regards the morbidity (11.5% and 9.6%, respectively) and the mortality (1.9% for both groups). Conclusion: Two-stage single-volume exchange transfusion proved to be more effective in reducing rebound serum bilirubin level post-exchange and in decreasing the need for repeated exchange transfusions.

Mortality After Pediatric Arterial Ischemic Stroke

We report the in-hospital mortality rate and identify risk factors among 915 neonates and 2273 children with AIS enrolled in an international registry. 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.