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ObjectiveThe aim of this multicentre study was to describe detailed characteristics of electrographic seizures in a cohort of neonates monitored with multichannel continuous electroencephalography (cEEG) in 6 European centres.MethodsNeonates of at least 36 weeks of gestation who required cEEG monitoring for clinical concerns were eligible, and were enrolled prospectively over 2 years from June 2013. Additional retrospective data were available from two centres for January 2011 to February 2014. Clinical data and EEGs were reviewed by expert neurophysiologists through a central server.ResultsOf 214 neonates who had recordings suitable for analysis, EEG seizures were confirmed in 75 (35%). The most common cause was hypoxic-ischaemic encephalopathy (44/75, 59%), followed by metabolic/genetic disorders (16/75, 21%) and stroke (10/75, 13%). The median number of seizures was 24 (IQR 9–51), and the median maximum hourly seizure burden in minutes per hour (MSB) was 21 min (IQR 11–32), with 21 (28%) having status epilepticus defined as MSB>30 min/hour. MSB developed later in neonates with a metabolic/genetic disorder. Over half (112/214, 52%) of the neonates were given at least one antiepileptic drug (AED) and both overtreatment and undertreatment was evident. When EEG monitoring was ongoing, 27 neonates (19%) with no electrographic seizures received AEDs. Fourteen neonates (19%) who did have electrographic seizures during cEEG monitoring did not receive an AED.ConclusionsOur results show that even with access to cEEG monitoring, neonatal seizures are frequent, difficult to recognise and difficult to treat.Oberservation study number NCT02160171

ObjectiveTo compare a low versus a higher threshold for intervention in preterm infants with posthaemorrhagic ventricular dilatation.DesignMulticentre randomised controlled trial (ISRCTN43171322).Setting14 neonatal intensive care units in six countries.Patients126 preterm infants ≤34 weeks gestation with ventricular dilatation after grade III–IV haemorrhage were randomised to low threshold (LT) (ventricular index (VI) >p97 and anterior horn width (AHW) >6 mm) or higher threshold (HT) (VI>p97+4 mm and AHW >10 mm).InterventionCerebrospinal fluid tapping by lumbar punctures (LPs) (max 3), followed by taps from a ventricular reservoir, to reduce VI, and eventually a ventriculoperitoneal (VP) shunt if stabilisation of the VI below the p97+4 mm did not occur.Composite main outcome measureVP shunt or death.Results19 of 64 (30%) LT infants and 23 of 62 (37%) HT infants were shunted or died (P=0.45). A VP shunt was inserted in 12/64 (19%) in the LT and 14/62 (23%) infants in the HT group. 7/12 (58%) LT infants and 1/14 (7%) HT infants required shunt revision (P<0.01). 62 of 64 (97%) LT infants and 36 of 62 (58%) HT infants had LPs (P<0.001). Reservoirs were inserted in 40 of 64 (62%) LT infants and 27 of 62 (43%) HT infants (P<0.05).ConclusionsThere was no significant difference in the primary composite outcome of VP shunt placement or death in infants with posthaemorrhagic ventricular dilatation who were treated at a lower versus a higher threshold for intervention. Infants treated at the lower threshold received more invasive procedures. Assessment of neurodevelopmental outcomes will provide further important information in assessing the risks and benefits of the two treatment approaches.

Background Neonatal neurocritical care (NNCC) is a rapidly advancing field with limited fellowship training available in locally developed, non-accredited programs. A standardized survey aimed to understand the training backgrounds of individuals practicing NNCC, the structure of existing clinical NNCC services/training programs, and suggested clinical competencies for new graduates. Methods We developed an anonymous survey electronically sent to members of societies related to NNCC. Using the survey results as a guide, we discuss a competence by design (CBD) curriculum as a complementary approach to traditional time-based training. Results There were 82 responses to the survey from 30 countries; 95% of respondents were physicians. Thirty-one (42%) institutions reported having an NNCC service, 24 (29%) individuals reported formal NNCC training, 81% reported “significant variability” across NNCC training programs, and 88% were both in favor of standardizing training programs and pursuing formal accreditation for NNCC in the next 5 years. Conclusions The survey results demonstrate international interest in standardizing NNCC training and development of an accreditation or certification process. We propose consideration of a CBD-type curriculum as a training approach to focus on the development of specific NNCC competencies, rather than assuming the acquisition of these competencies based on time as a surrogate. Impact Continued growth and development in the field of NNCC has led to increasing need for training programs suited to meet the diverse needs of trainees from varied backgrounds. We present the results of an international survey that assessed the structure of existing training programs and the priority areas in which graduates must demonstrate competence, highlighting the combination of CBD and time-based training as one approach to address these recommendations. The survey results support interest in translating published training competencies, existing expertise, and infrastructure across centers into a standardized curriculum for NNCC including certification opportunities.

Brain oxygen consumption reflects neuronal activity and can therefore be used to investigate brain development or neuronal injury in neonates. In this paper we present the first results of a non-invasive MRI method to evaluate whole brain oxygen consumption in neonates. For this study 51 neonates were included. The T1 and T2 of blood in the sagittal sinus were fitted using the ‘T2 prepared tissue relaxation inversion recovery’ pulse sequence (T2-TRIR). From the T1 and the T2 of blood, the venous oxygenation and the oxygen extraction fraction (OEF) were calculated. The cerebral metabolic rate of oxygen (CMRO2) was the resultant of the venous oxygenation and arterial spin labeling whole brain cerebral blood flow (CBF) measurements. Venous oxygenation was 59±14% (mean±sd), OEF was 40±14%, CBF was 14±5ml/100g/min and CMRO2 was 30±12μmol/100g/min. The OEF in preterms at term-equivalent age was higher than in the preterms and in the infants with hypoxic–ischemic encephalopathy (p<0.01). The OEF, CBF and CMRO2 increased (p<0.01, <0.05 and <0.01, respectively) with postnatal age. We presented an MRI technique to evaluate whole-brain oxygen consumption in neonates non-invasively. The measured values are in line with reference values found by invasive measurement techniques. Preterms and infants with HIE demonstrated significant lower oxygen extraction fraction than the preterms at term-equivalent age. This could be due to decreased neuronal activity as a reflection of brain development or as a result of tissue damage, increased cerebral blood flow due to immature or impaired autoregulation, or could be caused by differences in postnatal age. •We present a non-invasive method which evaluates the brain oxygen metabolism.•The results are in agreement with reference values found by invasive techniques.•We were able to detect differences related to postnatal age and disease state.

The role of intrapartum asphyxia in neonatal encephalopathy and seizures in term infants is not clear, and antenatal factors are being implicated in the causal pathway for these disorders. However, there is no evidence that brain damage occurs before birth. We aimed to test the hypothesis that neonatal encephalopathy, early neonatal seizures, or both result from early antenatal insults. We used brain MRI or post-mortem examination in 351 fullterm infants with neonatal encephalopathy, early seizures, or both to distinguish between lesions acquired antenatally and those that developed in the intrapartum and early post-partum period. We excluded infants with major congenital malformations or obvious chromosomal disorders. Infants were divided into two groups: those with neonatal encephalopathy (with or without seizures), and evidence of perinatal asphyxia (group 1); and those without other evidence of encephalopathy, but who presented with seizures within 3 days of birth (group 2). Brain images showed evidence of an acute insult without established injury or atrophy in 197 (80%) of infants in group 1, MRI showed evidence of established injury in only 2 infants (<1%), although tiny foci of established white matter gliosis, in addition to acute injury, were seen in three of 21 on post-mortem examination. In group 2, acute focal damage was noted in 62 (69%) of infants. Two (3%) also had evidence of antenatal injury. Although our results cannot exclude the possibility that antenatal or genetic factors might predispose some infants to perinatal brain injury, our data strongly suggest that events in the immediate perinatal period are most important in neonatal brain injury.

Background: Perinatal arterial ischemic stroke (PAIS) is a leading cause of hemiparetic cerebral palsy. Multiple risk factors are associated with PAIS but studies are limited by small sample sizes and complex interactions. Unbiased machine learning applied to larger datasets may enable the development of robust predictive models. We aimed to use machine learning to identify risk factors predictive of PAIS and compare these to the existing literature. Methods: Common data elements of maternal, delivery, and neonatal factors were collected from three perinatal stroke registries and one control sample over a 7-year period. Inclusion criteria were MRI-confirmed PAIS, term birth, and idiopathic etiology. Random forest machine learning in combination with feature selection was used to develop a predictive model of PAIS. Results: Total of 2571 neonates were included (527 cases, 2044 controls). Risk factors uniquely identified through machine learning were infertility, miscarriage, primigravida, and meconium. When compared, factors identified through both literature-based selection and machine learning included maternal age, fetal tobacco exposure, intrapartum fever, and low 5-minute APGAR. Conclusions: Machine learning offers a novel, less biased method to identify PAIS predictors and complex pathophysiology. Our findings support known associations with concepts of placental disease and difficult fetal transition and may support early screening for PAIS.

Background: Early recognition of neonatal seizures secondary to pathogenic variants in potassium or sodium channel coding genes is crucial, as these seizures are often resistant to commonly used anti-seizure medications, but respond well to sodium-channel blockers. We report a unique aEEG pattern in neonatal seizures caused by SCN2A and KCNQ3 pathogenic variants, as well as adding regular EEG description. Methods: International multicentre descriptive study, reporting clinical characteristics, aEEG and conventional EEG findings of 10 newborns with seizures due to pathogenic SCN2A and KCNQ3 gene variants. Results: Seizures started in the first postnatal week. Seizure semiology typically included tonic posturing with apnea and desaturation. The aEEG showed a characteristic sequence of brief onset with a decrease, followed by a quick rise, and then postictal amplitude attenuation. This pattern correlated with bilateral attenuation in the EEG at onset, followed by rhythmic discharges ending in several seconds of post-ictal amplitude suppression. The majority of patients became seizure free upon initiation of a sodium-channel blocker. Conclusions: Neonatal seizures caused by SCN2A and KCNQ3 mutations can be recognized by a characteristic ictal aEEG pattern and clinical semiology. Awareness of this pattern facilitates the prompt initiation of precision treatment with sodium-channel blockers even before genetic test results are available.

Background Posthaemorrhagic ventricular dilatation (PHVD) is a serious complication of prematurity with subsequent disabilities. The diagnostic and therapeutic approaches to PHVD vary among neonatal centres. Aim To gain more insight into the different diagnostic criteria and treatment policies on PHVD among neonatal intensive care units across Europe. Methods A PHVD questionnaire was designed and sent to neonatologists in 37 European centres. Results A response was obtained from 32/37 (86%) centres located in 17 European countries. An overall estimated incidence of 7% was reported for severe intraventricular haemorrhages (grades III or IV according to Papile) among premature neonates born below 30 weeks’ gestation. Approximately half of these infants developed PHVD, of whom three-quarters required intervention. Ultrasound measurements of ventricular size were most commonly used to diagnose PHVD (94%). No consensus existed on which ventricular parameters needed to be enlarged and when to start treatment of PHVD. Early intervention (ie, initiated after the ventricular index (VI) exceeded the 97th percentile (p97) according to Levene) was provided in 8/32 centres (25%), whereas 23/32 centres (72%) first started therapy once the VI had crossed the p97+4 mm line and/or when neonates presented with a progressive increase in head circumference or with clinical symptoms of raised intracranial pressure. Wide variation was seen with respect to the applied therapy modalities for cerebrospinal fluid drainage. Conclusion This survey shows that diagnostic and therapeutic approaches to neonates with PHVD vary considerably. Uniform diagnostic criteria would facilitate studies to assess optimal timing and mode of intervention.

Background: Preterm infants with progressive post-hemorrhagic ventricular dilatation (PHVD) in the absence of associated parenchymal lesions may have a normal neurodevelopmental outcome. Objectives: To evaluate neurodevelopmental and cognitive outcomes among preterm infants with severe intraventricular hemorrhage (IVH) and PHVD requiring neurosurgical intervention. Methods: 32 preterm infants were admitted to a neonatal intensive care unit with PHVD requiring neurosurgical intervention, and were seen in the follow-up clinic for standardized cognitive, behavioral and neurological assessments between 5 and 8 years of age. Only preterm infants with a gestational age (GA) of <30 weeks, as well as preterm and full-term infants with PHVD and full-term infants with perinatal asphyxia are seen in our follow-up clinic at this age. There were 23 infants with a GA of <30 weeks in this study population. For these 23, matched controls were available and compared with the IVH group. Results: The majority (59.4%) had no impairments. None of the children with grade III and 8 of the 15 children (53%) with grade IV hemorrhage developed cerebral palsy. More subtle motor problems assessed with the Movement-ABC score were seen in 39% (n = 9); the mean IQ of all children was 93.4, and 29% of the children had an IQ of <85 (–1 SD). Timing of intervention did not have a beneficial effect on outcome. With respect to cognition, no significant differences were found between the IVH and the control group. Conclusion: The majority of the children in our population had no impairments. Cerebral palsy was not seen in any of the infants with a grade III hemorrhage.