Genomic testing in neonates.

Recent technological advances have led to the expansion of testing options for newborns with suspected rare genetic conditions, particularly in high-income healthcare settings. This article summarises the key genomic testing approaches, their indications and potential limitations.

Biometric assessments of the posterior fossa by fetal MRI: A systematic review.

BACKGROUND: Posterior fossa abnormalities (PFAs) are commonly identified within routine screening and are a frequent indication for fetal magnetic resonance imaging (MRI). Although biometric measurements of the posterior fossa (PF) are established on fetal ultrasound and MRI, qualitative visual assessments are predominantly used to differentiate PFAs. OBJECTIVES: This systematic review aimed to assess 2-dimensional (2D) biometric measurements currently in use for assessing the PF on fetal MRI to delineate different PFAs. METHODS: The protocol was registered (PROSPERO ID CRD42019142162). Eligible studies included T2-weighted MRI PF measurements in fetuses with and without PFAs, including measurements of the PF, or other brain areas relevant to PFAs. RESULTS: 59 studies were included - 6859 fetuses had 62 2D PF and related measurements. These included linear, area and angular measurements, representing measures of PF size, cerebellum/vermis, brainstem, and supratentorial measurements. 11 measurements were used in 10 or more studies and at least 1200 fetuses. These dimensions were used to characterise normal for gestational age, diagnose a range of pathologies, and predict outcome. CONCLUSION: A selection of validated 2D biometric measurements of the PF on fetal MRI may be useful for identification of PFA in different clinical settings. Consistent use of these measures, both clinically and for research, is recommended.

Improved fetal blood oxygenation and placental estimated measurements of diffusion-weighted MRI using data-driven Bayesian modeling.

PURPOSE: Motion correction in placental DW-MRI is challenging due to maternal breathing motion, maternal movements, and rapid intensity changes. Parameter estimates are usually obtained using least-squares methods for voxel-wise fitting; however, they typically give noisy estimates due to low signal-to-noise ratio. We introduce a model-driven registration (MDR) technique which incorporates a placenta-specific signal model into the registration process, and we present a Bayesian approach for Diffusion-rElaxation Combined Imaging for Detailed placental Evaluation model to obtain individual and population trends in estimated parameters. METHODS: MDR exploits the fact that a placenta signal model is available and thus we incorporate it into the registration to generate a series of target images. The proposed registration method is compared to a pre-existing method used for DCE-MRI data making use of principal components analysis. The Bayesian shrinkage prior (BSP) method has no user-defined parameters and therefore measures of parameter variation in a region of interest are determined by the data alone. The MDR method and the Bayesian approach were evaluated on 10 control 4D DW-MRI singleton placental data. RESULTS: MDR method improves the alignment of placenta data compared to the pre-existing method. It also shows a further reduction of the residual error between the data and the fit. BSP approach showed higher precision leading to more clearly apparent spatial features in the parameter maps. Placental fetal oxygen saturation (FO2 ) showed a negative linear correlation with gestational age. CONCLUSIONS: The proposed pipeline provides a robust framework for registering DW-MRI data and analyzing longitudinal changes of placental function.

Separating fetal and maternal placenta circulations using multiparametric MRI.

PURPOSE: The placenta is a vital organ for the exchange of oxygen, nutrients, and waste products between fetus and mother. The placenta may suffer from several pathologies, which affect this fetal-maternal exchange, thus the flow properties of the placenta are of interest in determining the course of pregnancy. In this work, we propose a new multiparametric model for placental tissue signal in MRI. METHODS: We describe a method that separates fetal and maternal flow characteristics of the placenta using a 3-compartment model comprising fast and slowly circulating fluid pools, and a tissue pool is fitted to overlapping multiecho T2 relaxometry and diffusion MRI with low b-values. We implemented the combined model and acquisition on a standard 1.5 Tesla clinical system with acquisition taking less than 20 minutes. RESULTS: We apply this combined acquisition in 6 control singleton placentas. Mean myometrial T2 relaxation time was 123.63 (±6.71) ms. Mean T2 relaxation time of maternal blood was 202.17 (±92.98) ms. In the placenta, mean T2 relaxation time of the fetal blood component was 144.89 (±54.42) ms. Mean ratio of maternal to fetal blood volume was 1.16 (±0.6), and mean fetal blood saturation was 72.93 (±20.11)% across all 6 cases. CONCLUSION: The novel acquisition in this work allows the measurement of histologically relevant physical parameters, such as the relative proportions of vascular spaces. In the placenta, this may help us to better understand the physiological properties of the tissue in disease.

Longitudinal development in the preterm thalamus and posterior white matter: MRI correlations between diffusion weighted imaging and T2 relaxometry.

Infants born prematurely are at increased risk of adverse neurodevelopmental outcome. The measurement of white matter tissue composition and structure can help predict functional performance. Specifically, measurements of myelination and indicators of myelination status in the preterm brain could be predictive of later neurological outcome. Quantitative imaging of myelin could thus serve to develop biomarkers for prognosis or therapeutic intervention; however, accurate estimation of myelin content is difficult. This work combines diffusion MRI and multi-component T2 relaxation measurements in a group of 37 infants born very preterm and scanned between 27 and 58 weeks equivalent gestational age. Seven infants have longitudinal data at two time points that we analyze in detail. Our aim is to show that measurement of the myelin water fraction is achievable using widely available pulse sequences and state-of-the-art algorithmic modeling of the MR imaging procedure and that a multi-component fitting routine to multi-shell diffusion weighted data can show differences in neurite density and local spatial arrangement in grey and white matter. Inference on the myelin water fraction allows us to demonstrate that the change in diffusion properties of the preterm thalamus is not solely due to myelination (that increase in myelin content accounts for about a third of the observed changes) whilst the decrease in the posterior white matter T2 has no significant component that is due to myelin water content. This work applies multi-modal advanced quantitative neuroimaging to investigate changing tissue properties in the longitudinal setting. Hum Brain Mapp 37:2479-2492, 2016. © 2016 Wiley Periodicals, Inc.

In Vivo Measurement of Cerebral Mitochondrial Metabolism Using Broadband Near Infrared Spectroscopy Following Neonatal Stroke.

Neonatal stroke presents with features of encephalopathy and can result in significant morbidity and mortality. We investigated the cerebral metabolic and haemodynamic changes following neonatal stroke in a term infant at 24 h of life. Changes in oxidation state of cytochrome-c-oxidase (oxCCO) concentration were monitored along with changes in oxy- and deoxy- haemoglobin using a new broadband near-infrared spectroscopy (NIRS) system. Repeated transient changes in cerebral haemodynamics and metabolism were noted over a 3-h study period with decrease in oxyhaemoglobin (HbO2), deoxy haemoglobin (HHb) and oxCCO in both cerebral hemispheres without significant changes in systemic observations. A clear asymmetry was noted in the degree of change between the two cerebral hemispheres. Changes in cerebral oxygenation (measured as HbDiff=HbO2-HHb) and cerebral metabolism (measured as oxCCO) were highly coupled on the injured side of the brain.

Longitudinal measurement of the developing grey matter in preterm subjects using multi-modal MRI.

Preterm birth is a major public health concern, with the severity and occurrence of adverse outcome increasing with earlier delivery. Being born preterm disrupts a time of rapid brain development: in addition to volumetric growth, the cortex folds, myelination is occurring and there are changes on the cellular level. These neurological events have been imaged non-invasively using diffusion-weighted (DW) MRI. In this population, there has been a focus on examining diffusion in the white matter, but the grey matter is also critically important for neurological health. We acquired multi-shell high-resolution diffusion data on 12 infants born at ≤ 28 weeks of gestational age at two time-points: once when stable after birth, and again at term-equivalent age. We used the Neurite Orientation Dispersion and Density Imaging model (NODDI) (Zhang et al., 2012) to analyse the changes in the cerebral cortex and the thalamus, both grey matter regions. We showed region-dependent changes in NODDI parameters over the preterm period, highlighting underlying changes specific to the microstructure. This work is the first time that NODDI parameters have been evaluated in both the cortical and the thalamic grey matter as a function of age in preterm infants, offering a unique insight into neuro-development in this at-risk population.

Preterm birth affects the developmental synergy between cortical folding and cortical connectivity observed on multimodal MRI.

The survival rates of infants born prematurely have improved as a result of advances in neonatal care, although there remains an increased risk of subsequent disability. Accurate measurement of the shape and appearance of the very preterm brain at term-equivalent age may guide the development of predictive biomarkers of neurological outcome. We demonstrate in 92 preterm infants (born at an average gestational age of 27.0±2.7weeks) scanned at term equivalent age (scanned at 40.4±1.74weeks) that the cortical sulcation ratio varies spatially over the cortical surface at term equivalent age and correlates significantly with gestational age at birth (r=0.49,p<0.0001). In the underlying white matter, fractional anisotropy of local white matter regions correlated significantly with gestational age at birth at term equivalent age (for the genu of the corpus callosum r=0.26,p=0.02 and for the splenium r=0.52,p<0.001) and in addition the fractional anisotropy in these local regions varies according to location. Finally, we demonstrate that connectivity measurements from tractography correlate significantly and specifically with the sulcation ratio of the overlying cortical surface at term equivalent age in a subgroup of 20 infants (r={0.67,0.61,0.86}, p={0.004,0.01,0.00002}) for tract systems emanating from the left and right corticospinal tracts and the corpus callosum respectively). Combined, these results suggest a close relationship between the cortical surface phenotype and underlying white matter structure assessed by diffusion weighted MRI. The spatial surface pattern may allow inference on the connectivity and developmental trajectory of the underlying white matter complementary to diffusion imaging and this result may guide the development of biomarkers of functional outcome.

White matter NAA/Cho and Cho/Cr ratios at MR spectroscopy are predictive of motor outcome in preterm infants.

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSION: 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.

AdaPT: An adaptive preterm segmentation algorithm for neonatal brain MRI.

Advances in neonatal care have improved the survival of infants born prematurely although these infants remain at increased risk of adverse neurodevelopmental outcome. The measurement of white matter structure and features of the cortical surface can help define biomarkers that predict this risk. The measurement of these structures relies upon accurate automated segmentation routines, but these are often confounded by neonatal-specific imaging difficulties including poor contrast, low resolution, partial volume effects and the presence of significant natural and pathological anatomical variability. In this work we develop and evaluate an adaptive preterm multi-modal maximum a posteriori expectation-maximisation segmentation algorithm (AdaPT) incorporating an iterative relaxation strategy that adapts the tissue proportion priors toward the subject data. Also incorporated are intensity non-uniformity correction, a spatial homogeneity term in the form of a Markov random field and furthermore, the proposed method explicitly models the partial volume effect specifically mitigating the neonatal specific grey and white matter contrast inversion. Spatial priors are iteratively relaxed, enabling the segmentation of images with high anatomical disparity from a normal population. Experiments performed on a clinical cohort of 92 infants are validated against manual segmentation of normal and pathological cortical grey matter, cerebellum and ventricular volumes. Dice overlap scores increase significantly when compared to a widely-used maximum likelihood expectation maximisation algorithm for pathological cortical grey matter, cerebellum and ventricular volumes. Adaptive maximum a posteriori expectation maximisation is shown to be a useful tool for accurate and robust neonatal brain segmentation.

Regional neonatal brain absolute thermometry by 1H MRS.

Therapeutic hypothermia is standard care for infants with moderate to severe encephalopathy. (1) H MRS thermometry (MRSt) measures regional brain absolute temperature using the temperature-dependent water chemical shift. This study evaluates the clinical feasibility of MRSt in human neonates, and correlates white matter (WM) and thalamus (Thal) MRSt with conventional rectal temperature (Trectal ) measurement. Fifty-six infants born at term underwent perinatal MRSt for suspected hypoxic-ischaemic brain injury and 33 infants born preterm had MRSt at a term-equivalent age; 56 of the 89 had Trectal measured after MRSt of either a Thal or posterior WM voxel, or both. MRSt used point-resolved spectroscopy (no water suppression; TR = 1370 ms; TE = 288 ms; 1.5 × 1.5 × 1.5 cm(3) Thal and 1.1 × 1.3 × 1.4 cm(3) WM voxels). Time domain data were phase and frequency corrected before summation and motion-corrupted data were excluded from further analysis using simple criteria [preprocessing + quality assurance (QA)]. Two published water temperature-dependence calibrations [both using cerebral creatine (Cr), choline (Cho) and N-acetylaspartate (Naa) as independent reference peaks] were compared. The temperature measurements derived from Cr, Cho and Naa were combined to give a single amplitude-weighted combination temperature (TAWC ). WM and Thal TAWC correlated linearly with Trectal (Thal slope, 0.82 ± 0.04, R(2) = 0.85, p < 0.05; WM slope, 0.95 ± 0.04, R(2) = 0.78, p < 0.05). Preprocessing + QA improved the correlation between WM TAWC and Trectal (R(2) increased from 0.27 to 0.78, p < 0.001). Both calibration datasets showed specific inconsistencies between the temperatures calculated using Cr, Cho and Naa reference peaks when applied to this neonatal dataset. Neonatal MRSt is clinically feasible. Preprocessing + QA improved MRSt reliability in WM. The consideration of MRSt calibration internal biases is necessary before combining MRSt temperatures from multiple reference peaks to obtain TAWC.

Post-mortem apparent resolution of fetal ventriculomegaly: evidence from magnetic resonance imaging.

OBJECTIVE: This study aims to determine the accuracy of post-mortem magnetic resonance imaging (MRI) and autopsy for confirmation of sonographically detected fetal ventriculomegaly. METHODS: This study uses retrospective review of fetuses with sonographically diagnosed ventriculomegaly, where the pregnancy was terminated and post-mortem examination was performed during a period in which post-mortem MRI was being offered. RESULTS: Sixteen cases were identified. In nine (56%), autopsy and/or post-mortem MRI confirmed the prenatal findings. In the other seven, both autopsy and post-mortem MRI demonstrated no ventriculomegaly, but antenatal MRI confirmed the ultrasound findings in 6/7 cases where it had been performed. Post-mortem investigations confirmed antenatal findings in 8/9 cases with severe ventriculomegaly (posterior horn measurement >15 mm), whereas only 2/7 in which ventriculomegaly was not confirmed had severe ventriculomegaly. CONCLUSIONS: Post-mortem examination, both by traditional neuropathological examination, and post-mortem MRI may fail to confirm prenatal ventriculomegaly in around half of cases. The post-mortem MRI findings indicate that this is due to resolution of ventriculomegaly rather than autopsy artefact, and is presumably a consequence of post-mortem fluid redistribution. Parents should be advised before termination of pregnancy that post-mortem confirmation of ventriculomegaly, especially in mild cases, may not be possible. Antenatal MRI may be a better approach for confirming prenatal ultrasound findings.

Clinical value of cortical bursting in preterm infants with intraventricular haemorrhage.

BACKGROUND: In healthy preterm infants, cortical burst rate and temporal dynamics predict important measures such as brain growth. We hypothesised that in preterm infants with germinal matrix-intraventricular haemorrhage (GM-IVH), cortical bursting could provide prognostic information. AIMS: We determined how cortical bursting was influenced by the injury, and whether this was related to developmental outcome. STUDY DESIGN: Single-centre retrospective cohort study at University College London Hospitals, UK. SUBJECTS: 33 infants with GM-IVH ≥ grade II (median gestational age: 25 weeks). OUTCOME MEASURES: We identified 47 EEGs acquired between 24 and 40 weeks corrected gestational age as part of routine clinical care. In a subset of 33 EEGs from 25 infants with asymmetric injury, we used the least-affected hemisphere as an internal comparison. We tested whether cortical burst rate predicted survival without severe impairment (median 2 years follow-up). RESULTS: In asymmetric injury, cortical burst rate was lower over the worst- than least-affected hemisphere, and bursts over the worst-affected hemisphere were less likely to immediately follow bursts over the least-affected hemisphere than vice versa. Overall, burst rate was lower in cases of GM-IVH with parenchymal involvement, relative to milder structural injury grades. Higher burst rate modestly predicted survival without severe language (AUC 0.673) or motor impairment (AUC 0.667), which was partly mediated by structural injury grade. CONCLUSIONS: Cortical bursting can index the functional injury after GM-IVH: perturbed burst initiation (rate) and propagation (inter-hemispheric dynamics) likely reflect associated grey matter and white matter damage. Higher cortical burst rate is reassuring for a positive outcome.

Use of super resolution reconstruction MRI for surgical planning in Placenta accreta spectrum disorder: Case series.

INTRODUCTION: Comprehensive imaging using ultrasound and MRI of placenta accreta spectrum (PAS) aims to prevent catastrophic haemorrhage and maternal death. Standard MRI of the placenta is limited by between-slice motion which can be mitigated by super-resolution reconstruction (SRR) MRI. We applied SRR in suspected PAS cases to determine its ability to enhance anatomical placental assessment and predict adverse maternal outcome. METHODS: Suspected PAS patients (n = 22) underwent MRI at a gestational age (weeks + days) of (32+3±3+2, range (27+1-38+6)). SRR of the placental-myometrial-bladder interface involving rigid motion correction of acquired MRI slices combined with robust outlier detection to reconstruct an isotropic high-resolution volume, was achieved in twelve. 2D MRI or SRR images alone, and paired data were assessed by four radiologists in three review rounds. All radiologists were blinded to results of the ultrasound, original MR image reports, case outcomes, and PAS diagnosis. A Random Forest Classification model was used to highlight the most predictive pathological MRI markers for major obstetric haemorrhage (MOH), bladder adherence (BA), and placental attachment depth (PAD). RESULTS: At delivery, four patients had placenta praevia with no abnormal attachment, two were clinically diagnosed with PAS, and six had histopathological PAS confirmation. Pathological MRI markers (T2-dark intraplacental bands, and loss of retroplacental T2-hypointense line) predicting MOH were more visible using SRR imaging (accuracy 0.73), in comparison to 2D MRI or paired imaging. Bladder wall interruption, predicting BA, was only easily detected by paired imaging (accuracy 0.72). Better detection of certain pathological markers predicting PAD was found using 2D MRI (placental bulge and myometrial thinning (accuracy 0.81)), and SRR (loss of retroplacental T2-hypointense line (accuracy 0.82)). DISCUSSION: The addition of SRR to 2D MRI potentially improved anatomical assessment of certain pathological MRI markers of abnormal placentation that predict maternal morbidity which may benefit surgical planning.

Comparison of diagnoses of early-onset sepsis associated with use of Sepsis Risk Calculator versus NICE CG149: a prospective, population-wide cohort study in London, UK, 2020-2021.

OBJECTIVE: We sought to compare the incidence of early-onset sepsis (EOS) in infants ≥34 weeks' gestation identified >24 hours after birth, in hospitals using the Kaiser Permanente Sepsis Risk Calculator (SRC) with hospitals using the National Institute for Health and Care Excellence (NICE) guidance. DESIGN AND SETTING: Prospective observational population-wide cohort study involving all 26 hospitals with neonatal units colocated with maternity services across London (10 using SRC, 16 using NICE). PARTICIPANTS: All live births ≥34 weeks' gestation between September 2020 and August 2021. OUTCOME MEASURES: EOS was defined as isolation of a bacterial pathogen in the blood or cerebrospinal fluid (CSF) culture from birth to 7 days of age. We evaluated the incidence of EOS identified by culture obtained >24 hours to 7 days after birth. We also evaluated the rate empiric antibiotics were commenced >24 hours to 7 days after birth, for a duration of ≥5 days, with negative blood or CSF cultures. RESULTS: Of 99 683 live births, 42 952 (43%) were born in SRC hospitals and 56 731 (57%) in NICE hospitals. The overall incidence of EOS (<72 hours) was 0.64/1000 live births. The incidence of EOS identified >24 hours was 2.3/100 000 (n=1) for SRC vs 7.1/100 000 (n=4) for NICE (OR 0.5, 95% CI (0.1 to 2.7)). This corresponded to (1/20) 5% (SRC) vs (4/45) 8.9% (NICE) of EOS cases (χ=0.3, p=0.59). Empiric antibiotics were commenced >24 hours to 7 days after birth in 4.4/1000 (n=187) for SRC vs 2.9/1000 (n=158) for NICE (OR 1.5, 95% CI (1.2 to 1.9)). 3111 (7%) infants received antibiotics in the first 24 hours in SRC hospitals vs 8428 (15%) in NICE hospitals. CONCLUSION: There was no significant difference in the incidence of EOS identified >24 hours after birth between SRC and NICE hospitals. SRC use was associated with 50% fewer infants receiving antibiotics in the first 24 hours of life.

TNF gene cluster deletion abolishes lipopolysaccharide-mediated sensitization of the neonatal brain to hypoxic ischemic insult.

In the current study, we explored the role of TNF cluster cytokines on the lipopolysaccharide (LPS)-mediated, synergistic increase in brain injury after hypoxic ischemic insult in postnatal day 7 mice. Pretreatment with moderate doses of LPS (0.3 µg/g) resulted in particularly pronounced synergistic injury within 12 h. Systemic application of LPS alone resulted in a strong upregulation of inflammation-associated cytokines TNFα, LTß, interleukin (IL) 1ß, IL6, chemokines, such as CXCL1, and adhesion molecules E-Selectin, P-Selectin and intercellular adhesion molecule-1 (ICAM1), as well as a trend toward increased LTα levels in day 7 mouse forebrain. In addition, it was also associated with strong activation of brain blood vessel endothelia and local microglial cells. Here, deletion of the entire TNF gene cluster, removing TNFα, LTß and LTα completely abolished endotoxin-mediated increase in the volume of cerebral infarct. Interestingly, the same deletion also prevented endothelial and microglial activation following application of LPS alone, suggesting the involvement of these cell types in bringing about the LPS-mediated sensitization to neonatal brain injury.

Distribution of pH changes in mouse neonatal hypoxic-ischaemic insult.

We assessed the distribution in brain pH after neonatal hypoxic-ischaemic insult and its correlation with local injury. Postnatal day 7 mice were injected with neutral red and underwent left carotid occlusion and exposure to 8% oxygen. Images captured from the cut surface of snap-frozen brain were used to calculate the pH from the blue-green absorbance ratios. Carotid occlusion alone had no effect, but combined with hypoxia caused rapid, biphasic pH decline, with the first plateau at 15-30 min, and the second at 60-90 min. The ipsilateral dorsal cortex, hippocampus, striatum and thalamus were most affected. Contralateral pH initially showed only 30% of the ipsilateral decline, becoming more acidotic with increasing duration. Systemic blood analysis revealed, compared with hypoxia alone, that combined insult caused a 63% decrease in blood glucose (1.3 ± 0.2 mM), a 2-fold increase in circulating lactate (17.7 ± 2.9 mM), a reduction in CO(2) to 1.9 ± 0.1 kPa and a drop in pH (7.26 ± 0.06). Re-oxygenation resulted in the normalisation of systemic changes, as well as a global alkaline rebound in brain pH at 4-6 h. A topographic comparison of brain injury showed only a partial correlation with pH changes, with the severest injury occurring in the ipsilateral hippocampus and sparing acidic parts of the contralateral cortex.

Prognostic value of neonatal EEG following therapeutic hypothermia in survivors of hypoxic-ischemic encephalopathy.

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.