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Highlights • Higher power of cortical bursts after postnatal day 3 predicted worse cognitive, language and motor outcomes. • Association between cortical bursts and outcome was independent of structural MRI findings. • EEG may provide additional information by indexing persistent active mechanisms that support recovery or exacerbate damage., Objective Early prediction of neurological deficits following neonatal hypoxic-ischemic encephalopathy (HIE) may help to target support. Neonatal animal models suggest that recovery following hypoxia-ischemia depends upon cortical bursting. To test whether this holds in human neonates, we correlated the magnitude of cortical bursting during recovery (≥postnatal day 3) with neurodevelopmental outcomes. Methods We identified 41 surviving infants who received therapeutic hypothermia for HIE (classification at hospital discharge: 19 mild, 18 moderate, 4 severe) and had 9-channel electroencephalography (EEG) recordings as part of their routine care. We correlated burst power with Bayley-III cognitive, motor and language scores at median 24 months. To examine whether EEG offered additional prognostic information, we controlled for structural MRI findings. Results Higher power of central and occipital cortical bursts predicted worse cognitive and language outcomes, and higher power of central cortical bursts predicted worse motor outcome, all independently of structural MRI findings. Conclusions Clinical EEG after postnatal day 3 may provide additional prognostic information by indexing persistent active mechanisms that either support recovery or exacerbate brain damage, especially in infants with less severe encephalopathy. Significance These findings could allow for the effect of clinical interventions in the neonatal period to be studied instantaneously in the future.

ObjectiveTo describe the cognitive, language and motor developmental trajectories of children born very preterm and to identify perinatal factors that predict the trajectories.DesignData from a cohort of 1142 infants born at Main outcome measuresDevelopmental trajectory SITAR models for Bayley-III cognitive, language (receptive and expressive communication subscales) and motor (fine and gross motor subscales) scores.ResultsThe successfully fitted SITAR models explained 62% of variance in cognitive development, 68% in receptive communication, 53% in fine motor and 68% in the gross motor development. There was too much variation in the expressive communication subscale to fit a SITAR model. The rate of development (gradient of the curve) best explains the variation in trajectories of development in all domains. Lower gestational age, lower birth weight and male sex significantly predicted a slower rate of development.ConclusionThe rate of development, rather than single time point developmental assessment, best predicts the very preterm infant’s developmental trajectory and should be the focus for monitoring and early intervention.

In August 2017, the National Institute for Health and Care Excellence (NICE) published a guideline entitled ‘Developmental follow-up of children and young people born preterm’.1 The 668-page guideline, with similar length in appendices, describes the risks of developmental problems, and the assessments and support recommended for children and young people born before 37+0 weeks’ gestation. The Guideline Committee included paediatric and neonatal clinicians, therapists, psychologists, researchers in neonatology and two lay members. Extensive research has been conducted in the UK on outcomes of prematurity through the EPICure studies,2 and several individual units, regions and networks have developed local guidelines.3 However, there has been no previous standardised guideline on developmental follow-up for these babies. In 2009, the 2-year assessment for those born before 30+0 weeks’ gestation was added to the toolkit in neonatology from the Department of Health,4 and is now in the National Neonatal Audit Programme as a standard of care for the management of children, as well as a measure of perinatal and neonatal outcomes.5 However, there is still wide variation in the provision of the 2-year assessment for premature babies throughout the UK,6 with partial data available for just 60% of these babies.5 This NICE guideline on developmental follow-up of the premature baby is welcome, as there is an urgent need for an adequately funded, equipped, staffed and effective surveillance service for this vulnerable population.

Necrotising enterocolitis (NEC) in preterm babies is a serious gastrointestinal emergency with potentially devastating consequences. Prompt and accurate diagnosis continues to be a challenge for health professionals. Early identification of clinical warning signs is extremely important, but the diagnosis relies heavily on the interpretation of abdominal radiographs. Postgraduate training of paediatricians and neonatologists in neonatal abdominal radiography is scarce, and there is variability of radiological input to neonatal services. Lack of a standardised approach and descriptive terminology for interpretation may result in inadequate communication between clinical and surgical teams, inaccurate diagnosis, inappropriate treatment, and unnecessary cessation of feeds and transfers to surgical units. This paper offers a guide designed for the doctor who on a busy night shift needs to interpret an abdominal radiograph and decide on a differential diagnosis of NEC in a preterm baby. It helps to provide structure and standardisation to interpretation of radiological signs using a comprehensive but simple method to support the clinical diagnosis. Our aim is to enhance the correct diagnosis of NEC.

Hypoxic ischemic encephalopathy (HIE) leads to significant morbidity and mortality. Impaired autoregulation after hypoxia-ischaemia has been suggested to contribute further to injury. Thalamic lactate/N-Acetylasperate (Lac/NAA) peak area ratio of > 0.3 on proton (1H) magnetic resonance spectroscopy (MRS) is associated with poor neurodevelopment outcome following HIE. Cytochrome-c-oxidase (CCO) plays a central role in mitochondrial oxidative metabolism and ATP synthesis. Using a novel broadband NIRS system, we investigated the impact of pressure passivity of cerebral metabolism (CCO), oxygenation (haemoglobin difference (HbD)) and cerebral blood volume (total haemoglobin (HbT)) in 23 term infants following HIE during therapeutic hypothermia (HT). Sixty-minute epochs of data from each infant were studied using wavelet analysis at a mean age of 48 h. Wavelet semblance (a measure of phase difference) was calculated to compare reactivity between mean arterial blood pressure (MABP) with oxCCO, HbD and HbT. OxCCO-MABP semblance correlated with thalamic Lac/NAA (r = 0.48, p = 0.02). OxCCO-MABP semblance also differed between groups of infants with mild to moderate and severe injury measured using brain MRI score (p = 0.04), thalamic Lac/NAA (p = 0.04) and neurodevelopmental outcome at one year (p = 0.04). Pressure passive changes in cerebral metabolism were associated with injury severity indicated by thalamic Lac/NAA, MRI scores and neurodevelopmental assessment at one year of age.

To determine (a) whether diffuse white matter injury of prematurity is associated with an increased choline (Cho)-to-creatine (Cr) ratio and a reduced N-acetylaspartate (NAA)-to-Cho ratio and whether these measures can be used as biomarkers of outcome and (b) if changes in peak area metabolite ratios at magnetic resonance (MR) spectroscopy are associated with changes in T2 and fractional anisotropy (FA) at MR imaging.The local ethics committee approved this study, and informed parental consent was obtained for each infant. At term-equivalent age, 43 infants born at less than 32 weeks gestation underwent conventional and quantitative diffusion-tensor and T2-weighted MR imaging. Single-voxel point-resolved proton (hydrogen 1) MR spectroscopy was performed from a 2-cm(3) voxel centered in the posterior periventricular white matter. Outcome was evaluated by using Bayley scales at a corrected age of 1 year. Associations were investigated with Pearson product moment or Spearman rank order correlation. Differences in ratios in infants with and infants without impairment were tested by using t tests.NAA/Cho and Cho/Cr ratios correlated with the scaled gross motor score and the composite motor score, independent of gestational age (P.05). FA at diffusion-tensor MR imaging and T2 at MR imaging correlated with the NAA/Cho ratio (P.05 for both) but not with the Cho/Cr ratio. Infants with motor scores of less than 85 (impaired) had an increased Cho/Cr ratio (P.03) and a reduced NAA/Cho ratio (P.01) compared to those without impairment. A combination of increased Cho/Cr ratio and decreased NAA/Cho ratio predicted impaired motor outcome at a corrected age of 1 year with a sensitivity of 0.80 (95% confidence interval [CI]: 0.57, 0.94) and a specificity of 0.80 (95% CI: 0.66, 0.88).The combination of Cho/Cr and NAA/Cho ratios measured in the posterior periventricular white matter at term-equivalent age is predictive of motor outcome at 1 year in infants born at less than 32 weeks gestation.

ObjectiveBrain proton (1H) magnetic resonance spectroscopy (MRS) lactate/N-acetylaspartate (Lac/NAA) peak area ratio is used for prognostication in neonatal encephalopathy (NE). At 3 Tesla in NE babies, the objectives were to assess: (1) sensitivity and specificity of basal ganglia and thalamus (BGT) 1H MRS Lac/NAA for the prediction of Bayley III outcomes at 2 years using optimised metabolite fitting (Tarquin) with threonine and total NAA; (2) prediction of motor outcome with diffusion-weighted MRI; (3) BGT Lac/NAA correlation with the National Institute of Child Health and Human Development (NICHD) MRI score.Subjects and methods55 (16 inborn, 39 outborn) infants at 39w+5 d (35w+5d–42w+0d) with NE admitted between February 2012 and August 2014 to University College London Hospitals for therapeutic hypothermia underwent MRI and 1H MRS at 3T on day 2–14 (median day 5). MRIs were scored. Bayley III was assessed at 24 (22–26) months.Results16 babies died (1 inborn, 15 outborn); 20, 19 and 21 babies had poor motor, cognitive and language outcomes. Using a threshold of 0.39, sensitivity and specificity of BGT Lac/NAA for 2-year motor outcome was 100% and 97%, cognition 90% and 97% and language 81% and 97%, respectively. Sensitivity and specificity for motor outcome of mean diffusivity (threshold 0.001 mm2/s) up to day 9 was 72% and 100% and fractional anisotropy (threshold 0.198) was 39% and 94%, respectively. Lac/NAA correlated with BGT injury on NICHD scores (2A, 2B, 3).ConclusionBGT Lac/NAA on 1H MRS at 3T within 14 days accurately predicts 2-year motor, cognitive and language outcome and may be a marker directing decisions for therapies after cooling.

Introduction Despite cooling, adverse outcomes are seen in up to half of the surviving infants after neonatal encephalopathy. A number of novel adjunct drug therapies with cooling have been shown to be highly neuroprotective in animal studies, and are currently awaiting clinical translation. Rigorous evaluation of these therapies in phase II trials using surrogate MR biomarkers may speed up their bench to bedside translation. A recent systematic review of single-centre studies has suggested that MR spectroscopy biomarkers offer the best promise; however, the prognostic accuracy of these biomarkers in cooled encephalopathic babies in a multicentre setting using different MR scan makers is not known. Methods and analysis The MR scanners (3 T; Philips, Siemens, GE) in all the participating sites will be harmonised using phantom experiments and healthy adult volunteers before the start of the study. We will then recruit 180 encephalopathic infants treated with whole body cooling from the participating centres. MRI and spectroscopy will be performed within 2 weeks of birth. Neurodevelopmental outcomes will be assessed at 18–24 months of age. Agreement between MR cerebral biomarkers and neurodevelopmental outcome will be reported. The sample size is calculated using the ‘rule of 10’, generally used to calculate the sample size requirements for developing prognostic models. Considering 9 parameters, we require 9×10 adverse events, which suggest that a total sample size of 180 is required. Ethics and dissemination Human Research Ethics Committee approvals have been received from Brent Research Ethics Committee (London), and from Imperial College London (Sponsor). We will submit the results of the study to relevant journals and offer national and international presentations. Trial registration number Clinical Trials.gov Number: NCT01309711.