Ca Ryan

Defining the gap between electrographic seizure burden, clinical expression and staff recognition of neonatal seizures

Background: Neonatal seizures are often subclinical, making accurate diagnosis difficult. Objective: To describe the clinical manifestations of electrographic seizures recorded on continuous video-EEG, and to compare this description with the recognition of clinical seizures by experienced neonatal staff. Methods: Term infants, at risk of seizures, were monitored by continuous 12-channel video-EEG from <6 hours of birth for up to 72 hours. All clinical seizures were recorded by experienced neonatal staff on individual seizure charts. Video-EEG recordings were subsequently analysed. The number, duration and clinical expression of electrographic seizures were calculated (in seconds), and compared with the seizures clinically suspected by the neonatal staff. Results: Of 51 infants enrolled, nine had electrographic seizures. A further three had clinically suspected seizures, without associated electrographic abnormality. Of the total 526 electrographic seizures, 179 (34%) had clinical manifestations evident on the simultaneous video recording. The clinical seizure activity corresponded to 18.8% of the total electrographic seizure burden. Overdiagnosis also occurred frequently. Of the 177 clinically suspected seizure episodes documented by staff, 48 (27%) had corresponding electrographic evidence of seizure activity Thus, only 9% (48/526) of electrographic seizures were accompanied by clinical manifestations, which were identified and documented by neonatal staff. Conclusion: Only one-third of neonatal EEG seizures displays clinical signs on simultaneous video recordings. Moreover, two-thirds of these clinical manifestations are unrecognised, or misinterpreted by experienced neonatal staff. In the recognition and management of neonatal seizures clinical diagnosis alone is not enough.

Early EEG Findings in Hypoxic-Ischemic Encephalopathy Predict Outcomes at 2 Years

OBJECTIVE: We examined the evolution of electroencephalographic (EEG) changes after hypoxic injury. METHODS: Continuous, multichannel, video-EEG was recorded for term infants with hypoxic-ischemic encephalopathy, from <6 hours to 72 hours after delivery. One-hour segments at 6, 12, 24, and 48 hours of age of the EEG were analyzed visually, and neurologic outcome was assessed at 24 months. RESULTS: Forty-four infants completed neurodevelopmental follow-up. Of those, 20 (45%) had abnormal outcomes. The EEG grade assigned correlated significantly with outcome. EEG abnormalities improved with time, with the worst EEG grade seen on the earliest recording in all cases. The best predictive ability was seen at 6 hours of age (area under the receiver operator characteristic curve: 0.958 [95% confidence interval: 0.88–1.04]; P = .000). Normal/mildly abnormal EEG results at 6, 12, or 24 hours had 100% positive predictive values for normal outcomes and negative predictive values of 67% to 76%. By 48 hours, many of the EEG findings had improved significantly. This led to the positive predictive value of abnormal EEG results being greater at 48 hours (93%), with a concurrent negative predictive value of 71%. EEG features that were associated with abnormal outcomes were background amplitude of <30 μV, interburst interval of >30 seconds, electrographic seizures, and absence of sleep-wake cycling at 48 hours. CONCLUSIONS: Early EEG is a reliable predictor of outcome in HIE. A normal or mildly abnormal EEG results within 6 hours after birth were associated with normal neurodevelopmental outcomes at 24 months.

Comparison of three manual ventilation devices using an intubated mannequin

Objective: To compare three devices for manual neonatal ventilation. Design: Participants performed a two minute period of ventilation using a self inflating device, an anaesthesia bag with attached manometer, and a Neopuff device. An intubated neonatal mannequin, approximating a 1 kg infant with functional lungs, was used for the study. Target ventilation variables included a rate of 40 breaths per minute, peak inspiratory pressure (PIP) of 20 cm H2O, and positive end expiratory pressure (PEEP) of 4 cm H2O. The circuit was attached to a laptop computer for data recording. Results: Thirty five participants were enrolled, including consultant neonatologists, paediatricians, and anaesthetists, paediatric and anaesthetic registrars, and neonatal nurses. The maximum PIP recorded using the self inflating bag, anaesthetic bag, and Neopuff device were 75.9, 35.5, and 22.4 cm H2O respectively. There were significant differences between the devices for mean PIP (30.7, 18.1, and 20.1 cm H2O), mean PEEP (0.2, 2.8, and 4.4 cm H2O), mean airway pressure (7.6, 8.5, and 10.9 cm H2O), % total breaths ⩽ 21 cm H2O PIP (39%, 92%, and 98%), and % total breaths ⩾ 30 cm H2O PIP (45%, 0, and 0). There was no difference between doctors and allied health professionals for the variables examined. Conclusion: The anaesthetic bag with manometer and Neopuff device both facilitate accurate and reproducible manual ventilation. Self inflating devices without modifications are not as consistent by comparison and should incorporate a manometer and a PEEP device, particularly when used for resuscitation of very low birthweight infants.

Mining the microbiota of the neonatal gastrointestinal tract for conjugated linoleic acid-producing bifidobacteria.

ABSTRACT This study was designed to isolate different strains of the genus Bifidobacterium from the fecal material of neonates and to assess their ability to produce the cis-9, trans-11 conjugated linoleic acid (CLA) isomer from free linoleic acid. Fecal material was collected from 24 neonates aged between 3 days and 2 months in a neonatal unit (Erinville Hospital, Cork, Ireland). A total of 46 isolates from six neonates were confirmed to be Bifidobacterium species based on a combination of the fructose-6-phosphate phosphoketolase assay, RAPD [random(ly) amplified polymorphic DNA] PCR, pulsed-field gel electrophoresis (PFGE), and partial 16S ribosomal DNA sequencing. Interestingly, only 1 of the 11 neonates that had received antibiotic treatment produced bifidobacteria. PFGE after genomic digestion with the restriction enzyme XbaI demonstrated that the bifidobacteria population displayed considerable genomic diversity among the neonates, with each containing between one and five dominant strains, whereas 11 different macro restriction patterns were obtained. In only one case did a single strain appear in two neonates. All genetically distinct strains were then screened for CLA production after 72 h of incubation with 0.5 mg of free linoleic acid ml−1 by using gas-liquid chromatography. The most efficient producers belonged to the species Bifidobacterium breve, of which two different strains converted 29 and 27% of the free linoleic acid to the cis-9, trans-11 isomer per microgram of dry cells, respectively. In addition, a strain of Bifidobacterium bifidum showed a conversion rate of 18%/μg dry cells. The ability of some Bifidobacterium strains to produce CLA could be another human health-promoting property linked to members of the genus, given that this metabolite has demonstrated anticarcinogenic activity in vitro and in vivo.

Early blood glucose profile and neurodevelopmental outcome at two years in neonatal hypoxic-ischaemic encephalopathy

BackgroundTo examine the blood glucose profile and the relationship between blood glucose levels and neurodevelopmental outcome in term infants with hypoxic-ischaemic encephalopathy.MethodsBlood glucose values within 72 hours of birth were collected from 52 term infants with hypoxic-ischaemic encephalopathy. Hypoglycaemia [< 46.8 mg/dL (2.6 mmol/L)] and hyperglycaemia [> 150 mg/dL (8.3 mmol/L)] were correlated to neurodevelopmental outcome at 24 months of age.ResultsFour fifths of the 468 blood samples were in the normoglycaemic range (392/468:83.8%). Of the remaining 76 samples, 51.3% were in the hypoglycaemic range and (48.7%) were hyperglycaemic. A quarter of the hypoglycaemic samples (28.2%:11/39) and a third of the hyperglycaemic samples (32.4%:12/37) were recorded within the first 30 minutes of life. Mean (SD) blood glucose values did not differ between infants with normal and abnormal outcomes [4.89(2.28) mmol/L and 5.02(2.35) mmol/L, p value = 0.15] respectively. In term infants with hypoxic-ischaemic encephalopathy, early hypoglycaemia (between 0-6 hours of life) was associated with adverse outcome at 24 months of age [OR = 5.8, CI = 1.04-32)]. On multivariate analysis to adjust for grade of HIE this association was not statistically significant. Late hypoglycaemia (6-72 hours of life) was not associated with abnormal outcome [OR = 0.22, CI (0.04-1.14)]. The occurrence of hyperglycaemia was not associated with adverse outcome.ConclusionDuring the first 72 hours of life, blood glucose profile in infants with hypoxic-ischaemic encephalopathy varies widely despite a management protocol. Early hypoglycaemia (0-6 hours of life) was associated with severe HIE, and thereby; adverse outcome.

Prediction of Seizures in Asphyxiated Neonates: Correlation With Continuous Video-Electroencephalographic Monitoring

BACKGROUND. After perinatal asphyxia, predicting which infants will develop significant hypoxic-ischemic encephalopathy and neonatal seizures remains a difficult task. High-risk markers (Apgar score, acidosis, nucleated red blood cells, and resuscitation) have been used to predict neonatal seizures with varying success. The “3 strikes” of Apgar score of <5 at 5 minutes, pH <7.00, and need for intubation have been cited as having a positive predictive value of 80%. We examined whether the predictive values of these markers would be increased if early continuous electroencephalographic monitoring allowed us to accurately identify all neonatal seizures and to grade the encephalopathy. METHOD. We recruited term infants with perinatal asphyxia. Continuous video electroencephalography was commenced soon after birth and continued for 24 to 72 hours. The abilities of high-risk markers to predict electroencephalographic seizurs, background electroencephalographic activity, and Sarnat grade were examined. RESULTS. Forty-nine infants were suitable for analysis. Electrographic seizures occurred in 11 of the 49 infants. Encephalopathy was scored by using Sarnat grade (6, severe; 18, moderate; 25, mild) and electroencephalographic findings (4 inactive, 4 major abnormalities, 16 moderate abnormalities, and 25 normal/mildly abnormal). Apgar score of <5 at 5 minutes, pH <7.0, and the need for intubation had positive predictive values for neonatal seizures of 18%, 16%, and 21%, respectively. Combining these markers gave a positive predictive value of 25% and a negative predictive value of 77%. Substituting base deficit or lactate for pH in the 3-strikes model did not improve its predictive value. Apgar score of <5 at 5 minutes, nucleated red blood cells, and a base deficit less than −15 mEq/L showed some association with Sarnat grade. Only 5-minute Apgar score was significantly associated with both Sarnat grade and electroencephalographic grade. CONCLUSION. After perinatal asphyxia, neither the condition at birth nor the degree of metabolic acidosis reliably predict neonatal seizures.

Microbial Composition of Human Appendices from Patients following Appendectomy

ABSTRACT The human appendix has historically been considered a vestige of evolutionary development with an unknown function. While limited data are available on the microbial composition of the appendix, it has been postulated that this organ could serve as a microbial reservoir for repopulating the gastrointestinal tract in times of necessity. We aimed to explore the microbial composition of the human appendix, using high-throughput sequencing of the 16S rRNA gene V4 region. Seven patients, 5 to 25 years of age, presenting with symptoms of acute appendicitis were included in this study. Results showed considerable diversity and interindividual variability among the microbial composition of the appendix samples. In general, however, Firmicutes was the dominant phylum, with the majority of additional sequences being assigned at various levels to Proteobacteria, Bacteroidetes, Actinobacteria, and Fusobacteria. Despite the large diversity in the microbiota found within the appendix, however, a few major families and genera were found to comprise the majority of the sequences present. Interestingly, also, certain taxa not generally associated with the human intestine, including the oral pathogens Gemella, Parvimonas, and Fusobacterium, were identified among the appendix samples. The prevalence of genera such as Fusobacterium could also be linked to the severity of inflammation of the organ. We conclude that the human appendix contains a robust and varied microbiota distinct from the microbiotas in other niches within the human microbiome. The microbial composition of the human appendix is subject to extreme variability and comprises a diversity of biota that may play an important, as-yet-unknown role in human health. IMPORTANCE There are currently limited data available on the microbial composition of the human appendix. It has been suggested, however, that it may serve as a “safe house” for commensal bacteria that can reinoculate the gut at need. The present study is the first comprehensive view of the microbial composition of the appendix as determined by high-throughput sequencing. We have determined that the human appendix contains a wealth of microbes, including members of 15 phyla. Important information regarding the associated bacterial diversity of the appendix which will help determine the role, if any, the appendix microbiota has in human health is presented. There are currently limited data available on the microbial composition of the human appendix. It has been suggested, however, that it may serve as a “safe house” for commensal bacteria that can reinoculate the gut at need. The present study is the first comprehensive view of the microbial composition of the appendix as determined by high-throughput sequencing. We have determined that the human appendix contains a wealth of microbes, including members of 15 phyla. Important information regarding the associated bacterial diversity of the appendix which will help determine the role, if any, the appendix microbiota has in human health is presented.

Role of Gut Microbiota in Early Infant Development

Early colonization of the infant gastrointestinal tract is crucial for the overall health of the infant, and establishment and maintenance of non-pathogenic intestinal microbiota may reduce several neonatal inflammatory conditions. Much effort has therefore been devoted to manipulation of the composition of the microbiota through 1) the role of early infant nutrition, particularly breast milk, and supplementation of infant formula with prebiotics that positively influence the enteric microbiota by selectively promoting growth of beneficial bacteria and 2) oral administration of probiotic bacteria which when administered in adequate amounts confer a health benefit on the host. While the complex microbiota of the adult is difficult to change in the long-term, there is greater impact of the diet on infant microbiota as this is not as stable as in adults. Decreasing excessive use of antibiotics and increasing the use of pre- and probiotics have shown to be beneficial in the prevention of several important infant diseases such as necrotizing enterocolitis and atopic eczema as well as improvement of short and long-term health. This review addresses how the composition of the gut microbiota becomes established in early life, its relevance to infant health, and dietary means by which it can be manipulated.

Childhood cancer in Ireland: a population-based study

Background: Population-based studies of childhood cancer incidence, survival and mortality make an important contribution to monitoring the successful implementation of new treatment guidelines and to understanding the epidemiology of these diseases. Methods: We analysed incidence and survival data for cancers diagnosed in children under 15 years of age in the Republic of Ireland during 1994–2000 (the first 7 years of National Cancer Registry coverage), and longer term mortality trends. Results: World age-standardised incidence rates in Ireland averaged 142 cases per million children per year, slightly higher than the European average and slightly lower than the US average, although differences varied by diagnostic group. Observed 5-year survival in Ireland (79% overall) was slightly higher than European and US averages, and was significantly higher for acute non-lymphocytic leukaemia (67%) and (compared with the USA) significantly lower for Hodgkin lymphoma (83%). No significant increases in incidence rates were evident from the available 7 years’ data, either overall or for particular diagnostic groups. Rates of childhood cancer mortality have declined markedly since the 1950s. Conclusions: Data presented here are in line with other developed countries and suggest major improvements in treatment and consequent survival.

EEG in the healthy term newborn within 12 hours of birth

OBJECTIVE To characterise and quantify the EEG during sleep in healthy newborns in the early newborn period. METHODS Continuous multi-channel video-EEG data was recorded for up to 2 hours in normal newborns within 12 hours of birth. The total amount of active (AS) and quiet sleep (QS) was calculated in the first hour of recording. The EEG signal was quantitatively analysed for symmetry and synchrony. Spectral edge frequency (SEF), spectral entropy (H) and relative delta power (delta(R)) were calculated for a ten-minute segment of AS and QS in each recording. Paired t-test and Wilcoxon rank sum test were used for data analysis. RESULTS Thirty normal newborn babies were studied, 10 within 6 hours of birth and 20 between 6 and 12 hours. All babies showed continuous symmetrical and synchronous EEG activity and well-developed sleep-wake cycling (SWC) with the median percentage of AS--48.5% and QS--36.6%. Quantitative EEG analysis of sleep epochs showed that SEF and H were significantly higher (p<0.0001) and delta(R) was significantly lower (p<0.0001) in AS than in QS. CONCLUSION The normal newborn EEG shows symmetrical and synchronous continuous activity and well-developed SWC as early as within the first 6 hours of birth. Quantitative analysis of the EEG in the early postnatal period reveals differences in SEF, H and delta(R) for AS and QS periods. SIGNIFICANCE These findings may have implications for quantitative analysis of the newborn EEG, including the EEG of babies with hypoxic ischaemic encephalopathy.