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MRI of the brain is a critical tool in the diagnosis, evaluation, and management of neonatal encephalopathy (NE). More than simply a diagnostic and prognostic tool, MRI informs the biology, nature, and timing of the disease process resulting in NE, of which the largest single etiology is hypoxic-ischemic encephalopathy (HIE). Historically, 2 major patterns of injury were seen in HIE: a basal ganglia/thalamus predominant pattern and a watershed pattern of injury. The advent of therapeutic hypothermia for NE/HIE, alongside improvements in the application of imaging technology in newborn infants, has resulted in progressively more advanced MRI scoring systems., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Brain injury patterns of preterm infants with perinatal asphyxia (PA) are underreported. We aimed to explore brain magnetic resonance imaging (MRI) findings and associated neurodevelopmental outcomes in these newborns., Methods: Retrospective multicenter study included infants with gestational age (GA) 24.0-36.0 weeks and PA, defined as ≥2 of the following: (1) umbilical cord pH ≤7.0, (2) 5-min Apgar score ≤5, and (3) fetal distress or systemic effects of PA. Findings were compared between GA <28.0 (group 1), 28.0-31.9 (group 2), and 32.0-36.0 weeks (group 3). Early MRI (<36 weeks postmenstrual age or <10 postnatal days) was categorized according to predominant injury pattern, and MRI around term-equivalent age (TEA, 36.0-44.0 weeks and ≥10 postnatal days) using the Kidokoro score. Adverse outcomes included death, cerebral palsy, epilepsy, severe hearing/visual impairment, or neurodevelopment <-1 SD at 18-24 months corrected age., Results: One hundred nineteen infants with early MRI (n = 94) and/or MRI around TEA (n = 66) were included. Early MRI showed predominantly hemorrhagic injury in groups 1 (56%) and 2 (45%), and white matter (WM)/watershed injury in group 3 (43%). Around TEA, WM scores were highest in groups 2 and 3. Deep gray matter (DGM) (aOR 15.0, 95% CI: 3.8-58.9) and hemorrhagic injury on early MRI (aOR 2.5, 95% CI: 1.3-4.6) and Kidokoro WM (aOR 1.3, 95% CI: 1.0-1.6) and DGM sub-scores (aOR 4.8, 95% CI: 1.1-21.7) around TEA were associated with adverse neurodevelopmental outcomes., Conclusion: The brain injury patterns following PA in preterm infants differ across GA. Particularly DGM abnormalities are associated with adverse neurodevelopmental outcomes., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Background and Purpose: To apply and evaluate an intensity-based interpolation technique, enabling segmentation of motion-affected neonatal brain MRI., Methods: Moderate-late preterm infants were enrolled in a prospective cohort study (Brain Imaging in Moderate-late Preterm infants "BIMP-study") between August 2017 and November 2019. T2-weighted MRI was performed around term equivalent age on a 3T MRI. Scans without motion (n = 27 [24%], control group) and with moderate-severe motion (n = 33 [29%]) were included. Motion-affected slices were re-estimated using intensity-based shape-preserving cubic spline interpolation, and automatically segmented in eight structures. Quality of interpolation and segmentation was visually assessed for errors after interpolation. Reliability was tested using interpolated control group scans (18/54 axial slices). Structural similarity index (SSIM) was used to compare T2-weighted scans, and Sørensen-Dice was used to compare segmentation before and after interpolation. Finally, volumes of brain structures of the control group were used assessing sensitivity (absolute mean fraction difference) and bias (confidence interval of mean difference)., Results: Visually, segmentation of 25 scans (22%) with motion artifacts improved with interpolation, while segmentation of eight scans (7%) with adjacent motion-affected slices did not improve. Average SSIM was .895 and Sørensen-Dice coefficients ranged between .87 and .97. Absolute mean fraction difference was ≤0.17 for less than or equal to five interpolated slices. Confidence intervals revealed a small bias for cortical gray matter (0.14-3.07 cm 3 ), cerebrospinal fluid (0.39-1.65 cm 3 ), deep gray matter (0.74-1.01 cm 3 ), and brainstem volumes (0.07-0.28 cm 3 ) and a negative bias in white matter volumes (-4.47 to -1.65 cm 3 )., Conclusion: According to qualitative and quantitative assessment, intensity-based interpolation reduced the percentage of discarded scans from 29% to 7%., (© 2022 The Authors. Journal of Neuroimaging published by Wiley Periodicals LLC on behalf of American Society of Neuroimaging.)

Purpose: It is unknown whether frequently occurring mild brain lesions affect brain volumes in moderate (MP 2 ; 32 +0 -33 +6 weeks' gestation) and late (LP 3 ; 34 +0 -35 +6 weeks' gestation) preterm infants. Therefore, we aimed to investigate the effect of mild brain lesions on brain volumes in moderate-late preterm (MLPT 4 ) infants and to compare brain volumes between MP and LP infants., Methods: From August 2017 to November 2019, eligible MLPT infants born at Isala Women and Children's Hospital were enrolled in a prospective cohort study (Brain Imaging in Moderate-late Preterm infants 'BIMP-study'). MRI was performed around term equivalent age (TEA 5 ). MRI scans were assessed for (mild) brain lesions. T2-weighted images were used for automatic segmentation of eight brain structures. Linear regression analysis was performed to compare absolute and relative brain volumes between infants with and without mild brain lesions and between MP and LP infants., Results: 36 MP and 68 LP infants were included. In infants with mild brain lesions, intracranial volume (B = 27.4 cm 3 , p = 0.02), cerebrospinal fluid (B = 8.78 cm 3 , p = 0.01) and cerebellar volumes (B = 1.70 cm 3 , p = 0.03) were significantly larger compared to infants without mild brain lesions. After correction for weight and postmenstrual age at MRI, these volumes were no longer significantly different. LP infants had larger brain volumes than MP infants, but differences were not significant. Relative brain volumes showed no significant differences in both analyses., Conclusion: Neither having mild brain lesions, nor being born moderate prematurely affected brain volumes at TEA in MLPT infants., Competing Interests: Declarations of interest None., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Magnetic resonance imaging (MRI) scores have been well validated in moderate/severe hypoxic-ischemic encephalopathy (HIE). Infants with mild HIE can have different patterns of injury, yet different scores have not been compared in this group of infants. Our objective was to compare the ability of three = MRI scores to detect abnormalities in infants with mild HIE, and infants with moderate/severe HIE were included for comparison., Methods: This is a single-center prospective cohort study of infants ≥36 weeks' gestation with HIE born at a level III neonatal intensive care unit from 2017 to 2019. All infants with HIE underwent an MRI, but only infants with moderate/severe HIE underwent therapeutic hypothermia. At least two experienced MRI readers who were unaware of all clinical variables independently assigned three scores (Barkovich, NICHD NRN, and Weeke)., Results: A total of 42 newborns with varying HIE severity underwent MRI on day five of life. In the overall cohort, abnormalities were reported in three (7%) infants using the Barkovich, in 10 (24%) using the NICHD NRN, and in 24 (57%) using the Weeke score. Agreement was excellent for each score: Barkovich score (k = 1.0), NICHD NRN (k = 0.92), and Weeke score (k = 0.9)., Conclusions: Subtle injury due to mild HIE was detected with the highest frequency using the Weeke score, while inter-rater reliability was excellent for all three scores. These findings suggest that infants with mild HIE and subtle MRI abnormalities may benefit from detailed scoring systems, which is important for studies investigating the benefit of hypothermia in mild HIE., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Neonatal brain imaging undoubtedly can provide the most accurate information from which to determine whether cerebral palsy is likely to affect an individual infant born preterm. The sensitivity and specificity of that information is different between cranial ultrasound and MRI, depending on what approaches and sequences are used and the timing of the examinations. In this chapter we highlight the changing incidence of different patterns of brain injury in the preterm newborn and present a comparison of cranial ultrasound and MRI for predicting cerebral palsy in preterm infants affected by the commoner intracranial pathologies., (© 2020 Elsevier Ltd. All rights reserved.)

Background: Neonates with unilateral perinatal brain injury (UPBI) are at risk for developing unilateral spastic cerebral palsy (USCP). This study compares several predictors for USCP later in life., Methods: Twenty-one preterm and 24 term born infants with UPBI were included, with an MRI scan including diffusion tensor imaging (DTI) performed at term equivalent age or around 3 months after birth, respectively. T2-weighted images and DTI-based tractography were used to measure the surface area, diameter, and fractional anisotropy (FA) of both corticospinal tracts (CSTs). The hand assessment for infants (HAI) was performed before 5, between 5 and 8 and between 8 and 12 months of (corrected) age. Asymmetry indices were derived from all techniques and related to USCP at ≥2 years of age., Results: MRI measures and HAI scores were significantly lower for the affected compared to the unaffected side. Before 5 months of age, FA asymmetry on DTI yielded the highest area under the curve compared to conventional MRI and HAI., Conclusions: Prediction of USCP after UPBI is reliable using asymmetry of the CST on MRI, as well as clinical hand assessment. Before 5 months of age, DTI tractography provides strongest predictive information, while HAI specifically aids to prognosis of USCP at later age points.

Background: Post-haemorrhagic ventricular dilatation can be measured accurately by MRI. However, two-dimensional (2-D) cranial US can be used at the bedside on a daily basis., Objective: To assess whether the ventricular volume can be determined accurately using US., Materials and Methods: We included 31 preterm infants with germinal matrix intraventricular haemorrhage. Two-dimensional cranial US images were acquired and the ventricular index, anterior horn width and thalamo-occipital distance were measured. In addition, cranial MRI was performed. The ventricular volume on MRI was determined using a previously validated automatic segmentation algorithm. We obtained the correlation and created a linear model between MRI-derived ventricular volume and 2-D cranial US measurements., Results: The ventricular index, anterior horn width and thalamo-occipital distance as measured on 2-D cranial US were significantly associated with the volume of the ventricles as determined with MRI. A general linear model fitted the data best: ∛ventricular volume (ml) = 1.096 + 0.094 × anterior horn width (mm) + 0.020 × thalamo-occipital distance (mm) with R 2  = 0.831., Conclusion: The volume of the lateral ventricles of infants with germinal matrix intraventricular haemorrhage can be estimated using 2-D cranial US images by application of a model.

Objectives: To determine prevalence and risk factors for brain injury in infants with critical congenital heart disease (CHD) from 2 sites with different practice approaches who were scanned clinically., Study Design: Prospective, longitudinal cohort study (2016-2017) performed at Hospital for Sick Children Toronto (HSC) and Wilhelmina Children's Hospital Utrecht (WKZ), including 124 infants with cardiac surgery ≤60 days (HSC = 77; WKZ = 47). Magnetic resonance imaging was performed per clinical protocol, preoperatively (n = 100) and postoperatively (n = 120). Images were reviewed for multifocal (watershed, white matter injury) and focal ischemic injury (stroke, single white matter lesion)., Results: The prevalence of ischemic injury was 69% at HSC and 60% at WKZ (P = .20). Preoperative multifocal injury was associated with low cardiac output syndrome (OR, 4.6), which was equally present at HSC and WKZ (20% vs 28%; P = .38). Compared with WKZ, HSC had a higher prevalence of balloon-atrioseptostomy in transposition of the great arteries (83% vs 53%; P = .01) and more frequent preoperative focal injury (27% vs 6%; P = .06). Postoperatively, 30% of new multifocal injury could be attributed to postoperative low cardiac output syndrome, which was equally present at HSC and WKZ (38% vs 28%; P = .33). Postoperative focal injury was associated with intraoperative selective cerebral perfusion in CHD with arch obstruction at both sites (OR, 2.7). Compared with HSC, WKZ had more arch obstructions (62% vs 35%; P < .01) and a higher prevalence of new focal injury (36% vs 16%; P = .01)., Conclusions: Brain injury is common in clinical cohorts of infants with critical CHD and related to practice approaches. This study confirms that the high prevalence of brain injury in critical CHD is a clinical concern and does not simply reflect the inclusion criteria of published research studies., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Hypoxic-ischemic encephalopathy (HIE) in term-born infants can lead to memory problems. The hippocampus is important for long-term episodic memory. The primary aim was to investigate the effect of HIE on hippocampal volumes in 9- to 10-year-old children. The secondary aim was to investigate the association between hippocampal volumes and previously found impaired memory and cognitive functions in the current cohort., Methods: In total 26 children with mild HIE, 26 with moderate HIE, and 37 controls were included. The intelligence quotient (IQ) and memory were tested. A 3D-volumetric MRI was obtained. Brain segmentation was performed for hippocampal volumes and intracranial volume. The differences in hippocampal volumes, memory, and IQ between the groups were determined. Multivariable linear regression analyses were performed, including hippocampal volume as a percentage of intracranial volume as a dependent variable., Results: Smaller hippocampal volumes were found in moderate HIE (p < 0.001), with a trend toward smaller volumes in mild HIE, compared to controls. In multivariable linear regression analysis, hippocampal volume as a percentage of intracranial volume was significantly associated with long-term visuospatial memory., Conclusion: Children with moderate HIE had smaller hippocampal volumes than controls, with a trend toward smaller volumes following mild HIE. Reduced hippocampal volumes were associated with poorer long-term visuospatial memory.

Objective: The aim of this study was to evaluate whether a new MRI scoring system for preterm non-haemorrhagic white matter injury (WMI), derived from the analysis of the natural evolution of WMI throughout the neonatal period until term-equivalent age, can be used for outcome prediction., Methods: Eighty-two infants <36 weeks gestation with WMI diagnosed from sequential cranial ultrasound and confirmed on neonatal MRI were retrospectively included. WMI was classified in four grades of severity. Neurodevelopmental data at a median age of 24 months were analysed., Results: In 74 surviving children WMI severity was strongly associated with the presence and severity of cerebral palsy (CP) and other neurodevelopmental impairments (Spearman's rank correlation 0.88, p < 0.001). Only 3 children with grade I WMI (9%) developed CP (all ambulant) and their developmental scores were not different to those from the controls, although they started walking significantly later (p = 0.036). Of the 6 children with grade II, 83% developed CP (mild in most), whereas 91% of the 34 children with grade III had CP (moderate-severe in 76%) and all had some degree of neurodevelopmental impairment. Three children with grade III WMI did not develop CP; their imaging showed, in contrast to children who developed CP, that the cysts did not affect the corticospinal tracts; also, myelin in the posterior limb of the internal capsule appeared normal in 2 children and suboptimal in 1., Conclusions: This MRI scoring system for preterm WMI can be used to predict neurodevelopmental outcomes. Individualized assessment of the site of lesions and the progression of myelination improves prognostic accuracy., (© 2019 S. Karger AG, Basel.)

Objective: To study perioperative amplitude-integrated electroencephalography (aEEG) as an early marker for new brain injury in neonates requiring cardiac surgery for critical congenital heart disease (CHD)., Study Design: This retrospective observational cohort study investigated 76 neonates with critical CHD who underwent neonatal surgery. Perioperative aEEG recordings were evaluated for background pattern (BGP), sleep-wake cycling (SWC), and ictal discharges. Spontaneous activity transient (SAT) rate, inter-SAT interval (ISI), and percentage of time with an amplitude <5 µV were calculated. Routinely obtained preoperative and postoperative magnetic resonance imaging of the brain were reviewed for brain injury (moderate-severe white matter injury, stroke, intraparenchymal hemorrhage, or cerebral sinovenous thrombosis)., Results: Preoperatively, none of the neonates showed an abnormal BGP (burst suppression or worse) or ictal discharges. Postoperatively, abnormal BGP was seen in 18 neonates (24%; 95% CI, 14%-33%) and ictal discharges was seen in 13 neonates (17%; 95% CI, 8%-26%). Abnormal BGP and ictal discharges were more frequent in neonates with new postoperative brain injury (P = .08 and .01, respectively). Abnormal brain activity (ie, abnormal BGP or ictal discharges) was the single risk factor associated with new postoperative brain injury in multivariable logistic regression analysis (OR, 4.0; 95% CI, 1.3-12.3; P = .02). Postoperative SAT rate, ISI, or time <5 µV were not associated with new brain injury., Conclusion: Abnormal brain activity is an early, bedside marker of new brain injury in neonates undergoing cardiac surgery. Not only ictal discharges, but also abnormal BGP, should be considered a clear sign of underlying brain pathology., (Copyright © 2018 Elsevier Inc. All rights reserved.)

This study investigates the predictive ability of automatic quantitative brain MRI descriptors for the identification of infants with low cognitive and/or motor outcome at 2-3 years chronological age. MR brain images of 173 patients were acquired at 30 weeks postmenstrual age (PMA) (n = 86) and 40 weeks PMA (n = 153) between 2008 and 2013. Eight tissue volumes and measures of cortical morphology were automatically computed. A support vector machine classifier was employed to identify infants who exhibit low cognitive and/or motor outcome (<85) at 2-3 years chronological age as assessed by the Bayley scales. Based on the images acquired at 30 weeks PMA, the automatic identification resulted in an area under the receiver operation characteristic curve (AUC) of 0.78 for low cognitive outcome, and an AUC of 0.80 for low motor outcome. Identification based on the change of the descriptors between 30 and 40 weeks PMA (n = 66) resulted in an AUC of 0.80 for low cognitive outcome and an AUC of 0.85 for low motor outcome. This study provides evidence of the feasibility of identification of preterm infants at risk of cognitive and motor impairments based on descriptors automatically computed from images acquired at 30 and 40 weeks PMA.

Objective: To identify clinical risk factors for punctate white matter lesions (PWML) on early magnetic resonance imaging (MRI) in 2 cohorts of newborns born extremely preterm in different neonatal centers., Study Design: A total of 250 newborns born preterm at less than 28 weeks of gestation (mean 26.4 ± 1.1 weeks) with an early MRI were identified from 2 neonatal centers, in Vancouver, Canada (cohort A, n = 100) and Utrecht, the Netherlands (cohort B, n = 150). Cohort A was imaged as part of a prospective research study and cohort B was imaged as part of routine clinical care. PWML were defined as cluster type foci of hyperintensity on T1-weighted imaging and were identified at a mean postmenstrual age of 31.1 (±1.9) weeks. Multivariable analysis was used to identify clinical factors predictive of PWML., Results: Cluster type PWML were found in 47 newborns born extremely preterm (18.8%) and were more common in cohort A (32%) than in cohort B (10%). Newborns in cohort A generally were sicker than those in cohort B. Multivariable analyses revealed that greater birth weight (B = 0.002; P < .02), grade II-III intraventricular hemorrhage (B = 0.83; P < .02), and cohort A (B = 1.34; P < .0001) were independent predictors of PWML., Conclusion: Several risk factors for PWML on early MRI were identified. The interaction among birth weight, intraventricular hemorrhage, and other aspects of postnatal illness as risk factors for PWML warrants further investigation in newborns born extremely preterm and may help to identify modifiable risk factors for PWML., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Cortical folding mainly takes place in the third trimester of pregnancy and may therefore be influenced by preterm birth. The aim of this study was to evaluate the development of specific cortical structures between early age (around 30weeks postmenstrual age) and term-equivalent age (TEA, around 40weeks postmenstrual age) in 71 extremely preterm infants, and to associate this to clinical characteristics and neurodevelopmental outcome at two years of age. First, analysis showed that the central sulcus (CS), lateral fissure (LF) and insula (INS) were present at early MRI in all infants, whereas the other sulci (post-central sulcus [PCS], superior temporal sulcus [STS], superior [SFS] and inferior [IFS] frontal sulcus) were only seen in part of the infants. Relative growth from early to TEA examination was largest in the SFS. A rightward asymmetry of the surface area was seen in development between both examinations except for the LF, which showed a leftward asymmetry at both time points. Second, lower birth weight z-score, multiple pregnancy and prolonged mechanical ventilation showed negative effects on cortical folding of the CS, LF, INS, STS and PCS, mainly on the first examination, suggesting that sulci developing the earliest were the most affected by clinical factors. Finally, in this cohort, a clear association between cortical folding and neurodevelopmental outcome at two years corrected age was found, particularly for receptive language., (Copyright © 2016. Published by Elsevier Inc.)

Aim: To report on the neurological presentation and neuroimaging findings in newborn infants with incontinentia pigmenti., Method: The clinical and neurological course including neuroimaging and follow-up data of eight newborn infants with the neurological phenotype of incontinentia pigmenti were retrospectively reviewed., Results: While the clinical picture was polymorphic, the neurological manifestations were defined as encephalopathic and comprised lethargy and seizures in all but one of the infants. Magnetic resonance imaging (MRI) abnormalities were predominantly in the white matter. Diffusion-weighted imaging (DWI) was obtained during the acute phase in seven of the eight infants, showing restricted diffusion in the deep and subcortical white matter but also in the corpus callosum, basal ganglia, thalami, cerebellum, and cerebral peduncles. Susceptibility-weighted imaging (SWI), performed in five infants, showed a variable amount of signal loss, mainly in the white matter, within areas of restricted diffusion. Extensive MRI abnormalities in newborn infants were followed by abnormal neurodevelopment, with significant motor, cognitive, and/or visual problems., Interpretation: To assess the extent of central nervous system involvement, MRI is recommended in the clinical evaluation of infants with incontinentia pigmenti. They have a characteristic pattern of brain lesions seen on MRI, best recognized using DWI and SWI in the acute neonatal phase, which allow the identification of and distinction between ischaemic and haemorrhagic lesions., (© 2016 Mac Keith Press.)

Background: The evolution of non-hemorrhagic white matter injury (WMI) based on sequential magnetic resonance imaging (MRI) has not been well studied. Our aim was to describe sequential MRI findings in preterm infants with non-hemorrhagic WMI and to develop an MRI classification system for preterm WMI based on these findings., Methods: Eighty-two preterm infants (gestation ≤35 weeks) were retrospectively included. WMI was diagnosed and classified based on sequential cranial ultrasound (cUS) and confirmed on MRI., Results: 138 MRIs were obtained at three time-points: early (<2 weeks; n = 32), mid (2-6 weeks; n = 30) and term equivalent age (TEA; n = 76). 63 infants (77%) had 2 MRIs during the neonatal period. WMI was non-cystic in 35 and cystic in 47 infants. In infants with cystic-WMI early MRI showed extensive restricted diffusion abnormalities, cysts were already present in 3 infants; mid MRI showed focal or extensive cysts, without acute diffusion changes. A significant reduction in the size and/or extent of the cysts was observed in 32% of the infants between early/mid and TEA MRI. In 4/9 infants previously seen focal cysts were no longer identified at TEA. All infants with cystic WMI showed ≥2 additional findings at TEA: significant reduction in WM volume, mild-moderate irregular ventriculomegaly, several areas of increased signal intensity on T1-weighted-images, abnormal myelination of the PLIC, small thalami., Conclusion: In infants with extensive WM cysts at 2-6 weeks, cysts may be reduced in number or may even no longer be seen at TEA. A single MRI at TEA, without taking sequential cUS data and pre-TEA MRI findings into account, may underestimate the extent of WMI; based on these results we propose a new MRI classification for preterm non-hemorrhagic WMI.

Automatic segmentation in MR brain images is important for quantitative analysis in large-scale studies with images acquired at all ages. This paper presents a method for the automatic segmentation of MR brain images into a number of tissue classes using a convolutional neural network. To ensure that the method obtains accurate segmentation details as well as spatial consistency, the network uses multiple patch sizes and multiple convolution kernel sizes to acquire multi-scale information about each voxel. The method is not dependent on explicit features, but learns to recognise the information that is important for the classification based on training data. The method requires a single anatomical MR image only. The segmentation method is applied to five different data sets: coronal T 2 -weighted images of preterm infants acquired at 30 weeks postmenstrual age (PMA) and 40 weeks PMA, axial T 2 -weighted images of preterm infants acquired at 40 weeks PMA, axial T 1 -weighted images of ageing adults acquired at an average age of 70 years, and T 1 -weighted images of young adults acquired at an average age of 23 years. The method obtained the following average Dice coefficients over all segmented tissue classes for each data set, respectively: 0.87, 0.82, 0.84, 0.86, and 0.91. The results demonstrate that the method obtains accurate segmentations in all five sets, and hence demonstrates its robustness to differences in age and acquisition protocol.

Purpose: Visual field (VF) defects are common sequelae of perinatal arterial ischemic stroke (PAIS). The aim of this study was to investigate the predictive value of magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) for VF defects following PAIS., Methods: Nineteen infants with unilateral PAIS, who underwent conventional MRI (T1/T2) and DTI at three months of age and a VF examination later in life (median age 3.2 yrs) were included. Conventional T1-weighted MRI was used to assess asymmetry of the optic radiation (OR). DTI-based tractography of the bilateral OR was performed, and the average fractional anisotropy (FA), axial (λ1), radial (λ23) and mean diffusivity (MD) were extracted. Asymmetry of the OR on MRI and DTI was used as a predictor of VF defects using receiver operating characteristic (ROC) analysis., Results: Of the 19 infants, nine had a normal VF, eight had a VF defect (six hemianopia and two quadrantanopia), and two had an inconclusive VF test. The presence or absence of a VF defect could be correctly predicted using conventional MRI assessment in the majority of the infants, with an area under the curve (AUC) of 0.90 (95% CI 0.66-0.99). Prediction based on DTI parameter asymmetry indices showed an AUC of 0.96 (95% CI 0.74-1.00), 0.78 (95% CI 0.52-0.94), 0.93 (95% CI 0.70-1.00) and 0.90 (95% CI 0.66-0.99) for FA, λ1, λ23 and MD, respectively., Conclusions: VF defects following PAIS can be reliably predicted by assessment of asymmetry of the OR at three months on conventional MRI and DTI-based tractography with comparable predictive values. Conventional T1-weighted MRI can be used in clinical practice., (Copyright © 2015 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.)

There have been tremendous changes in the methods used to evaluate brain injury in the preterm infant in the past 30 years. In particular, major improvements have been made in how we use neuroimaging techniques and now magnetic resonance imaging (MRI) is used more often and considered complimentary to routine and sequential cranial ultrasound. The focus has shifted from severe lesions such as large intraventricular and parenchymal hemorrhages and cystic periventricular leukomalacia to assessing and understanding the etiology of more subtle noncystic white matter injury, punctate hemorrhage, and cerebellar lesions. The more severe lesions that dominated the early period of preterm neonatal brain imaging occur less frequently but are still associated with major disabilities, such as, cerebral palsy, while subtle white matter injury and cerebellar lesions are more often associated with cognitive and behavioral problems, which have become the most prevalent issues among the survivors of extremely preterm birth., (Georg Thieme Verlag KG Stuttgart · New York.)

Introduction: The cerebral cortex develops rapidly in the last trimester of pregnancy. In preterm infants, brain development is very vulnerable because of their often complicated extra-uterine conditions. The aim of this study was to quantitatively describe cortical development in a cohort of 85 preterm infants with and without brain injury imaged at 30 and 40 weeks postmenstrual age (PMA)., Methods: In the acquired T2-weighted MR images, unmyelinated white matter (UWM), cortical grey matter (CoGM), and cerebrospinal fluid in the extracerebral space (CSF) were automatically segmented. Based on these segmentations, cortical descriptors evaluating volume, surface area, thickness, gyrification index, and global mean curvature were computed at both time points, for the whole brain, as well as for the frontal, temporal, parietal, and occipital lobes separately. Additionally, visual scoring of brain abnormality was performed using a conventional scoring system at 40 weeks PMA., Results: The evaluated descriptors showed larger change in the occipital lobes than in the other lobes. Moreover, the cortical descriptors showed an association with the abnormality scores: gyrification index and global mean curvature decreased, whereas, interestingly, median cortical thickness increased with increasing abnormality score. This was more pronounced at 40 weeks PMA than at 30 weeks PMA, suggesting that the period between 30 and 40 weeks PMA might provide a window of opportunity for intervention to prevent delay in cortical development.

Aim: The aim of this study was to delineate aetiologies and explore the diagnostic value of cerebral magnetic resonance imaging (MRI) in addition to cranial ultrasonography (cUS) in infants presenting with neonatal seizures., Method: This retrospective cohort study comprised infants (gestational age 35.0-42.6wks) with seizures, confirmed by either continuous amplitude-integrated electroencephalography (aEEG) or standard EEG and admitted during a 14-year period to a level three neonatal intensive care unit (n=378; 216 males, 162 females; mean [SD] birthweight 3334g [594]). All infants underwent cUS and MRI (MRI on median of 5 days after birth, range 0-58d) within the first admission period., Results: An underlying aetiology was identified in 354 infants (93.7%). The most common aetiologies identified were hypoxic-ischaemic encephalopathy (46%), intracranial haemorrhage (12.2%), and perinatal arterial ischaemic stroke (10.6%). When comparing MRI with cUS in these 354 infants MRI showed new findings which did not become apparent on cUS, contributing to a diagnosis in 42 (11.9%) infants and providing additional information to cUS, contributing to a diagnosis in 141 (39.8%). cUS alone would have allowed a diagnosis in only 37.9% of infants (134/354)., Interpretation: Cerebral MRI contributed to making a diagnosis in the majority of infants. In 11.9% of infants the diagnosis would have been missed if only cUS were used and cerebral MRI added significantly to the information obtained in 39.8% of infants. These data suggest that cerebral MRI should be performed in all newborn infants presenting with EEG- or aEEG-confirmed seizures., (© 2014 Mac Keith Press.)

A number of algorithms for brain segmentation in preterm born infants have been published, but a reliable comparison of their performance is lacking. The NeoBrainS12 study (http://neobrains12.isi.uu.nl), providing three different image sets of preterm born infants, was set up to provide such a comparison. These sets are (i) axial scans acquired at 40 weeks corrected age, (ii) coronal scans acquired at 30 weeks corrected age and (iii) coronal scans acquired at 40 weeks corrected age. Each of these three sets consists of three T1- and T2-weighted MR images of the brain acquired with a 3T MRI scanner. The task was to segment cortical grey matter, non-myelinated and myelinated white matter, brainstem, basal ganglia and thalami, cerebellum, and cerebrospinal fluid in the ventricles and in the extracerebral space separately. Any team could upload the results and all segmentations were evaluated in the same way. This paper presents the results of eight participating teams. The results demonstrate that the participating methods were able to segment all tissue classes well, except myelinated white matter., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Aim: The aim of the study was to compare clinical and neuroimaging characteristics and neurodevelopmental outcome in preterm infants with a periventricular haemorrhagic infarction (PVHI) located in the temporal or frontal periventricular white matter., Method: The study was a retrospective hospital-based study of preterm infants with a frontal PVHI (n=21; 11 males, 10 females; mean birthweight 1527g; mean gestational age 30.3wks) or temporal PVHI (n=13; five males, eight females; mean birthweight 1205g; mean gestational age 30.2wks) admitted to the neonatal intensive care unit between 1990 and 2012. The clinical course, results of neuroimaging studies, and neurodevelopmental outcomes of preterm infants with a gestational age less than 34 weeks with a confirmed PVHI on early cranial ultrasonography and/or magnetic resonance imaging were reviewed. For assessment of neurodevelopmental outcome we used the Griffiths Mental Development Scales, the Movement Assessment Battery for Children, the Gross Motor Function Classification System, the Wechsler Preschool and Primary Scale of Intelligence, the Child Behavior Checklist, and ophthalmological assessment. An unfavourable neurodevelopmental outcome was defined as moderately or severely atypical neurological examination during the last visit: presence of cerebral palsy, epilepsy, a hearing or visual impairment, and/or atypical cognitive development (Griffiths Mental Development Scales developmental quotient or Wechsler Preschool and Primary Scale of Intelligence <85)., Results: Unfavourable outcome was observed in 12 out of 13 children with a temporal PVHI compared with six out of 21 children with a frontal PVHI (p=0.002). Only one of the included infants with a PVHI in the temporal white matter developed cerebral palsy, which was due to a parietal PVHI in the contralateral hemisphere. Cognitive impairment was noted in seven infants with a frontal PVHI and five with a temporal PVHI. There were more infants with a temporal PVHI who developed visual impairment (n=5) or behavioural problems (n=7) compared with those with a frontal PVHI (visual impairment (n=2), behavioural problems (n=3)., Interpretation: PVHI located in the temporal or frontal lobe is almost invariably related to a typical motor outcome, but carries a risk of cognitive, behavioural, and visual problems, especially in infants with a PVHI located in the temporal lobe., (© 2014 Mac Keith Press.)

Purpose: Volumetric measurements of neonatal brain tissues may be used as a biomarker for later neurodevelopmental outcome. We propose an automatic method for probabilistic brain segmentation in neonatal MRIs., Materials and Methods: In an IRB-approved study axial T1- and T2-weighted MR images were acquired at term-equivalent age for a preterm cohort of 108 neonates. A method for automatic probabilistic segmentation of the images into eight cerebral tissue classes was developed: cortical and central grey matter, unmyelinated and myelinated white matter, cerebrospinal fluid in the ventricles and in the extra cerebral space, brainstem and cerebellum. Segmentation is based on supervised pixel classification using intensity values and spatial positions of the image voxels. The method was trained and evaluated using leave-one-out experiments on seven images, for which an expert had set a reference standard manually. Subsequently, the method was applied to the remaining 101 scans, and the resulting segmentations were evaluated visually by three experts. Finally, volumes of the eight segmented tissue classes were determined for each patient., Results: The Dice similarity coefficients of the segmented tissue classes, except myelinated white matter, ranged from 0.75 to 0.92. Myelinated white matter was difficult to segment and the achieved Dice coefficient was 0.47. Visual analysis of the results demonstrated accurate segmentations of the eight tissue classes. The probabilistic segmentation method produced volumes that compared favorably with the reference standard., Conclusion: The proposed method provides accurate segmentation of neonatal brain MR images into all given tissue classes, except myelinated white matter. This is the one of the first methods that distinguishes cerebrospinal fluid in the ventricles from cerebrospinal fluid in the extracerebral space. This method might be helpful in predicting neurodevelopmental outcome and useful for evaluating neuroprotective clinical trials in neonates.

Objective: To investigate the relationship between placental pathology and pattern of brain injury in full-term infants with neonatal encephalopathy after a presumed hypoxic-ischemic insult., Study Design: The study group comprised full-term infants with neonatal encephalopathy subsequent to presumed hypoxia-ischemia with available placenta for analysis who underwent cerebral magnetic resonance imaging (MRI) within the first 15 days after birth. Macroscopic and microscopic characteristics of the placenta were assessed. The infants were classified according to the predominant pattern of brain injury detected on MRI: no injury, predominant white matter/watershed injury, predominant basal ganglia and thalami (BGT) injury, or white matter/watershed injury with BGT involvement. Maternal and perinatal clinical factors were recorded., Results: Placental tissue was available for analysis in 95 of 171 infants evaluated (56%). Among these 95 infants, 34 had no cerebral abnormalities on MRI, 27 had white matter/watershed injury, 18 had BGT injury, and 16 had white matter/watershed injury with BGT involvement. Chorioamnionitis was a common placental finding in both the infants without injury (59%) and those with white matter/BGT injury (56%). On multinomial logistic regression analysis, white matter/watershed injury with and without BGT involvement was associated with decreased placental maturation. Hypoglycemia was associated with an increased risk of the white matter/BGT injury pattern (OR,5.4; 95% CI, 1.4-21.4). The BGT injury pattern was associated with chronic villitis (OR, 12.7; 95% CI, 2.4-68.7). A placental weight <10th percentile appeared to be protective against brain injury, especially for the BGT pattern (OR, 0.1; 95% CI, 0.01-0.7)., Conclusion: Placental weight <10th percentile was mainly associated with normal cerebral MRI findings. Decreased placental maturation and hypoglycemia <2.0 mmol/L were associated with increased risk of white matter/watershed injury with or without BGT involvement. Chronic villitis was associated with BGT injury irrespective of white matter injury., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Background: Arterial spin labeling (ASL) magnetic resonance imaging (MRI) can evaluate brain perfusion in neonates noninvasively. The aim of this study was to investigate whether ASL MRI can demonstrate perfusion abnormalities in neonates diagnosed with perinatal arterial ischemic stroke (PAIS)., Methods: Pulsed ASL perfusion MR images were acquired in the subacute stage (5-6 d after birth) and at follow-up (13 d to 16 wk after birth) in four PAIS patients. Images were visually evaluated for hypo- and hyperperfusion. In addition, cerebral oxygenation was monitored using near infrared spectroscopy (NIRS)., Results: In three PAIS patients, ASL images showed hypoperfusion in the stroke area. In one of these, hyperperfusion was visualized in the periphery of the stroke area. In one PAIS patient, hyperperfusion was seen in the stroke area. In all infants, cerebral oxygenation was higher in the infarcted hemisphere as compared with the contralateral hemisphere. Follow-up ASL images showed partial recovery of perfusion in the stroke area., Conclusion: ASL perfusion MRI is able to reliably detect hypo- and hyperperfusion in PAIS patients and can be used to monitor the evolution of perfusion after an ischemic event.

Neuroimaging of preterm infants has become part of routine clinical care, but the question is often raised on how often cranial ultrasound should be done and whether every high risk preterm infant should at least have one MRI during the neonatal period. An increasing number of centres perform an MRI either at discharge or around term equivalent age, and a few centres have access to a magnet in or adjacent to the neonatal intensive care unit and are doing sequential MRIs. In this review, we try to discuss when best to perform these two neuroimaging techniques and the additional information each technique may provide.

Introduction: Punctate white matter lesions (PWML) are recognized with magnetic resonance imaging (MRI) as hypersignal on T1-weighted imaging and hyposignal on T2-weighted imaging. Our aim was to assess how often a hemorrhagic component was present in PWML using susceptibility-weighted imaging (SWI)., Methods: Seventeen preterm (gestational age, 25-34 weeks) and seven full-term infants (age at MRI, 37-42 weeks) with PWML were included. Seven preterm infants had sequential MRIs. PWML were diagnosed with conventional MRI and compared with SWI, where signal loss is suggestive of hemorrhage. The pattern of associated brain lesions was taken into account, and the percentage of lesions with signal loss on SWI was calculated for each infant., Results: A significantly higher percentage of signal loss on SWI (median, 93.9%) was found among infants with germinal matrix and intraventricular hemorrhage as the primary diagnosis (n = 8) compared to those with a primary diagnosis of white matter injury (n = 14; median, 14.2%; p < 0.01). In the infants with serial MRIs, a reduction in the number of PWML and/or signal loss on SWI was noted at term equivalent age. In the patient who died, cystic lesions, associated with hemorrhage and gliosis, were demonstrated on histology., Conclusions: SWI can distinguish hemorrhagic and non-hemorrhagic PWML. Signal loss on SWI was more common when PWML were associated with an intraventricular hemorrhage. Longitudinal imaging showed a decrease in the number of PWML over time, with some PWML no longer showing signal loss on SWI, suggesting early gliosis.

Objective: To assess the relation between patterns of brain injury on neonatal and childhood magnetic resonance imaging (MRI) and long-term neurodevelopmental outcome., Study Design: Neonatal (n = 34) and childhood MRIs (n = 77) were analyzed for 80 children with neonatal encephalopathy and for 51 control subjects during childhood. MRIs were graded as normal, mildly abnormal (white matter lesions), or moderately/severely abnormal (watershed injury, lesions in basal ganglia/thalamus or focal infarction). Severity of brain injury was related to different aspects of neurologic outcome: Total impairment score of the Movement Assessment Battery for Children, intelligence quotient score, cerebral palsy, postneonatal epilepsy, and need for special education. Seven children with neonatal encephalopathy required extracorporeal membrane oxygenation treatment., Results: Neonatal and childhood MRI were comparable in 25/33 children (75.8%, P < .001). Children with moderate/severe lesions on neonatal or childhood MRI more often had a total impairment score

Introduction: In recent years, intracranial hemorrhage (ICH) with parenchymal involvement has been diagnosed more often in full-term neonates due to improved neuroimaging techniques. The aim of this study is to describe clinical and neuroimaging data in the neonatal period and relate imaging findings to outcome in a hospital-based population admitted to a level 3 neonatal intensive care unit (NICU)., Methods: From our neuroimaging database, we retrospectively retrieved records and images of 53 term infants (1991-2008) in whom an imaging diagnosis of ICH with parenchymal involvement was made. Clinical data, including mode of delivery, clinical manifestations, neurological symptoms, extent and site of hemorrhage, neurosurgical intervention, and neurodevelopmental outcomes, were recorded., Results: Seventeen of the 53 term infants had infratentorial ICH, 20 had supratentorial ICH, and 16 had a combination of the two. Seizures were the most common presenting symptom (71.7%), another ten infants (18.9%) presented with apneic seizures, and five infants had no clinical signs but were admitted to our NICU because of perinatal asphyxia (n=2), respiratory distress (n=2), and development of posthemorrhagic ventricular dilatation (n=1). Continuous amplitude-integrated electroencephalography recordings were performed in all infants. Clinical or subclinical seizures were seen in 48/53 (90.6%) infants; all received anti-epileptic drugs. Thirteen of all 53 (24.5%) infants died. The lowest mortality rate was seen in infants with supratentorial ICH (10%). Three infants with a midline shift required craniotomy, six infants needed a subcutaneous reservoir due to outflow obstruction, and three subsequently required a ventriculoperitoneal shunt. The group with poor outcome (death or developmental quotient (DQ) <85) had a significantly lower 5-min Apgar score (p=.006). Follow-up data were available for 37/40 survivors aged at least 15 months. Patients were assessed with the Griffiths Mental Developmental Scales, and the mean DQ of all survivors was 97 (SD=12). Six infants (17%) had a DQ below 85 [two of them had cerebral palsy (CP)]. Three infants developed CP (8.6%); one had cerebellar ataxia, and two had hemiplegia., Conclusion: ICH with parenchymal involvement carries a risk of adverse neurological sequelae with a mortality of 24.5% and development of CP in 8.6%. The high mortality rate could partly be explained by associated perinatal asphyxia. Infants with supratentorial ICH had a lower, although not significant, mortality rate compared with infants with infratentorial ICH and infants with a combination of supratentorial ICH and infratentorial ICH. In spite of often large intraparenchymal lesions, 30 of the 34 survivors without CP (88.2%) had normal neurodevelopmental outcome at 15 months.

Enormous progress has been made in assessing the neonatal brain, using magnetic resonance imaging (MRI). In this review, we will describe the use of MRI and proton magnetic resonance spectroscopy in detecting different patterns of brain injury in (full-term) human neonates following hypoxic-ischaemic brain injury and indicate the relevance of these findings in predicting neurodevelopmental outcome.

Imaging data concerning infection of the central nervous system (CNS) in neonates are usually confined to small groups of infants. We have reviewed the imaging findings in 96 preterm and full-term infants admitted to our neonatal intensive care unit over a 15 year period. Neuro-imaging, especially cranial ultrasound (CUS) and magnetic resonance imaging (MRI) provided useful information; CUS allows the early and later detection of calcification, germinolytic and parenchymal cysts, ventricular dilatation and strands and ependymal abnormality; diffusion weighted imaging (DWI) is especially useful in the acute stage of bacterial and viral infections, while conventional MRI helps in the detection of neocortical dysplasia in CMV infection and defining cerebellar abnormality.

The internal capsule is highly visible on conventional magnetic resonance imaging (MRI). It is myelinating rapidly at term, and the time course of its maturation is well known. It carries the major motor and sensory pathways to and from the cortex and the spinal cord. Additionally, fibres from the thalamus pass through it connecting to most regions of the cortex. It is therefore of vital importance, and damage to it has severe consequences. Its abnormal appearance on conventional MRI is a good predictor of an abnormal motor outcome in different clinical situations encountered in perinatal medicine. Its normal appearance on conventional MR images at term age is usually associated with a relatively normal motor outcome. More recently, diffusion-weighted and diffusion tensor imaging have allowed a much more sophisticated assessment of its maturation and connectivity; this has already led to a better understanding of how its development is affected by preterm birth and by hypoxic-ischaemic brain injury. Future studies will assess the relevance of these findings not only for motor outcome but also for cognitive, visual and sensory abilities.

Aim: To assess the predictive value of early MRI and proton MR spectroscopy ((1)H-MRS), 11 full-term neonates with severe perinatal asphyxia were studied within 48 h after birth., Methods: T(1)- and T(2)-weighted MRI, diffusion-weighted MRI (DW-MRI), apparent diffusion coefficient of water (ADC) of the basal ganglia and parietal white matter, as well as (1)H-MRS of the basal ganglia were performed in a 1.5-Tesla magnetic field. Neurodevelopment was assessed in the survivors for at least 24 months., Results: Nine of the 11 neonates had a poor outcome (7 died, 2 developed cerebral palsy). All examinations were normal in the 2 neonates with a good outcome. T(1)- and T(2)-weighted MRI were abnormal in 7, DWI was abnormal in 7, ADC was abnormal in 5, and elevated lactate/N-acetylaspartate ratios using (1)H-MRS were seen in 7 of the 9 neonates with a poor outcome. None of these 9 had completely normal MRI or (1)H-MRS findings., Conclusions: Using a combination of T(1)- and T(2)-weighted MRI, DW-MRI, ADC measurements and (1)H-MRS within 48 h after severe perinatal asphyxia, no abnormalities were seen with any of these techniques in both neonates with a good outcome.

Background: 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., Methods: 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)., Findings: 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., Interpretation: 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.

Neuroimaging is widely used to aid in the diagnosis and clinical management of neonates with neonatal encephalopathy (NE). Yet, despite widespread use clinically, there are few published guidelines on neuroimaging for neonates with NE. This review outlines the primary patterns of brain injury associated with hypoxic-ischemic injury in neonates with NE and their frequency, associated neuropathological features, and risk factors. In addition, it provides an overview of neuroimaging methods, including the most widely used scoring systems used to characterize brain injury in these neonates and their utility as predictive biomarkers. Last, recommendations for neuroimaging in neonates with NE are presented.

ImportanceUnderstanding the role of chorioamnionitis, a major factor leading to preterm birth, in the pathogenesis of neonatal brain injury and adverse neurodevelopmental outcomes may help in identifying potentially modifiable perinatal variables affecting brain health and outcomes among children born preterm.ObjectiveTo evaluate whether histologic chorioamnionitis among neonates born very preterm is associated with intraventricular hemorrhage (IVH) and punctate white matter injury (WMI) or with adverse neurodevelopmental outcomes during early childhood.Design, setting, and participantsProspective cohort study conducted across 3 academic centers (from April 2006 to September 2013 in Canada, from March 2007 to March 2013 in the Netherlands, and from January 2004 to August 2011 in the United States). Children who were born preterm (24-32 weeks' gestation) and who had undergone a placental pathologic evaluation, magnetic resonance imaging as soon as clinically stable, and Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) assessments between 18 and 24 months' corrected age (CA) were included. Magnetic resonance imaging scans were assessed for grade of IVH and volume of punctate WMI. Data analysis occurred between December 2016 and January 2018. Final multivariable analyses examining the association of chorioamnionitis with motor and cognitive outcomes accounted for academic center and perinatal and postnatal factors.Main outcomes and measuresPunctate WMI volume and IVH detected on neonatal magnetic resonance imaging scans; motor and cognitive outcomes defined using Bayley-III assessments conducted among these children between 18 and 24 months' CA.ResultsOf 350 neonates (182 male) in the final cohort, 145 (41.4%) had histologic chorioamnionitis. Gestational age was significantly lower among those with chorioamnionitis (median, 26.4 weeks; interquartile range [IQR], 25.6-27.7 weeks) than among those without chorioamnionitis (median, 28.0 weeks; IQR, 27.0-29.7 weeks). Chorioamnionitis was not associated with IVH or WMI, nor was it associated with worse motor outcomes in univariable or multivariable analyses (adjusted Bayley-III motor score, -2.2; 95% CI, -5.6 to 1.3). Cognitive scores were marginally yet statistically significantly lower among children with chorioamnionitis (median, 105; IQR, 95-110) than among those without chorioamnionitis (median, 105; IQR, 100-115) in the univariable model. This difference was attenuated in the multivariable model (adjusted Bayley-III cognitive score, -3.0; 95% CI, -6.4 to 0.4).Conclusions and relevanceHistologic chorioamnionitis was not associated with IVH or WMI near birth or with worse cognitive or motor outcomes from 18 to 24 months' CA after accounting for perinatal factors. Postnatal factors attenuated the association between chorioamnionitis and neurodevelopmental outcomes, highlighting the importance of preventing postnatal illness, such as infection, to promote optimal outcomes among children born preterm.

Background: Magnetic resonance imaging (MRI) including diffusion-weighted imaging within seven days after birth is widely used to obtain prognostic information in neonatal encephalopathy (NE) following perinatal asphyxia. Later MRI could be useful for infants without a neonatal MRI or in the case of clinical concerns during follow-up. Therefore, this review evaluates the association between cranial MRI beyond the neonatal period and neurodevelopmental outcomes following NE. Methods: A systematic literature search was performed using PubMed and Embase on cranial MRI between 2 and 24 months after birth and neurodevelopmental outcomes following NE due to perinatal asphyxia. Two independent researchers performed the study selection and risk of bias analysis. Results were separately described for MRI before and after 18 months. Results: Twelve studies were included (high-quality n = 2, moderate-quality n = 6, low-quality n = 4). All reported on MRI at 2–18 months: seven studies demonstrated a significant association between the pattern and/or severity of injury and overall neurodevelopmental outcomes and three showed a significant association with motor outcome. There were insufficient data on non-motor outcomes and the association between MRI at 18–24 months and neurodevelopmental outcomes. Conclusions: Cranial MRI performed between 2 and 18 months after birth is associated with neurodevelopmental outcomes in NE following perinatal asphyxia. However, more data on the association with non-motor outcomes are needed. [ABSTRACT FROM AUTHOR]

The distinct placental angioarchitecture in monochorionic (MC) pregnancies increases the risk of complications such as twin–twin transfusion syndrome (TTTS), twin anemia polycythemia sequence (TAPS), and selective fetal growth restriction (sFGR). The aim of this systematic review was to evaluate the incidence, type, and severity of cerebral injury and structural brain development on fetal and/or neonatal cerebral magnetic resonance imaging (MRI) in MC twins with or without complications. Twenty-three studies were included, covering a wide range of complications observed during MC pregnancies, with studies involving sIUFD (n = 12), TTTS (n = 7), mixed complications (n = 2), TAPS (n = 1), and uncomplicated MC pregnancy (n = 1). TAPS and sFGR were largely underrepresented in the current literature. The included studies reported that MC pregnancies with single intrauterine fetal demise (sIUFD) are most at risk for cerebral injury during the fetal period. The overall median incidence of cerebral injury after sIUFD was 28.3% (0–55%). Severe antenatal cerebral injury after sIUFD was detected antenatally in 6.5% (0–36%) of the cases. Three of the included studies described the incidence, type, and severity of cerebral injury on neonatal MRI in MC twins. Structural brain development based on cerebral biometry was only assessed in two studies, revealing significantly smaller biometric measurements of the cerebrum in cases of single sIUFD or smaller twins compared to singleton pregnancies. To enhance our understanding of the potential risks and pathophysiological mechanisms associated with cerebral injury and structural brain development in MC twins, there is a need for future studies and standardized protocols using serial fetal and neonatal MRI imaging in addition to routine ultrasound imaging. [ABSTRACT FROM AUTHOR]

Seizures are common in neonates, but there is substantial management variability. The Neonatal Task Force of the International League Against Epilepsy (ILAE) developed evidence‐based recommendations about antiseizure medication (ASM) management in neonates in accordance with ILAE standards. Six priority questions were formulated, a systematic literature review and meta‐analysis were performed, and results were reported following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta‐Analyses) 2020 standards. Bias was evaluated using the Cochrane tool and risk of Bias in non‐randomised studies ‐ of interventions (ROBINS‐I), and quality of evidence was evaluated using grading of recommendations, assessment, development and evaluation (GRADE). If insufficient evidence was available, then expert opinion was sought using Delphi consensus methodology. The strength of recommendations was defined according to the ILAE Clinical Practice Guidelines development tool. There were six main recommendations. First, phenobarbital should be the first‐line ASM (evidence‐based recommendation) regardless of etiology (expert agreement), unless channelopathy is likely the cause for seizures (e.g., due to family history), in which case phenytoin or carbamazepine should be used. Second, among neonates with seizures not responding to first‐line ASM, phenytoin, levetiracetam, midazolam, or lidocaine may be used as a second‐line ASM (expert agreement). In neonates with cardiac disorders, levetiracetam may be the preferred second‐line ASM (expert agreement). Third, following cessation of acute provoked seizures without evidence for neonatal‐onset epilepsy, ASMs should be discontinued before discharge home, regardless of magnetic resonance imaging or electroencephalographic findings (expert agreement). Fourth, therapeutic hypothermia may reduce seizure burden in neonates with hypoxic–ischemic encephalopathy (evidence‐based recommendation). Fifth, treating neonatal seizures (including electrographic‐only seizures) to achieve a lower seizure burden may be associated with improved outcome (expert agreement). Sixth, a trial of pyridoxine may be attempted in neonates presenting with clinical features of vitamin B6‐dependent epilepsy and seizures unresponsive to second‐line ASM (expert agreement). Additional considerations include a standardized pathway for the management of neonatal seizures in each neonatal unit and informing parents/guardians about the diagnosis of seizures and initial treatment options. [ABSTRACT FROM AUTHOR]

Aim: To evaluate mammillary body abnormalities in school‐age children without cerebral palsy treated with therapeutic hypothermia for neonatal hypoxic–ischaemic encephalopathy (cases) and matched controls, and associations with cognitive outcome, hippocampal volume, and diffusivity in the mammillothalamic tract (MTT) and fornix. Method: Mammillary body abnormalities were scored from T1‐weighted magnetic resonance imaging (MRI) in 32 cases and 35 controls (median age [interquartile range] 7 years [6 years 7 months–7 years 7 months] and 7 years 4 months [6 years 7 months–7 years 7 months] respectively). Cognition was assessed using the Wechsler Intelligence Scale for Children, Fourth Edition. Hippocampal volume (normalized by total brain volume) was measured from T1‐weighted MRI. Radial diffusivity and fractional anisotropy were measured in the MTT and fornix, from diffusion‐weighted MRI using deterministic tractography. Results: More cases than controls had mammillary body abnormalities (34% vs 0%; p < 0.001). Cases with abnormal mammillary bodies had lower processing speed (p = 0.016) and full‐scale IQ (p = 0.028) than cases without abnormal mammillary bodies, and lower scores than controls in all cognitive domains (p < 0.05). Cases with abnormal mammillary bodies had smaller hippocampi (left p = 0.016; right p = 0.004) and increased radial diffusivity in the right MTT (p = 0.004) compared with cases without mammillary body abnormalities. Interpretation: Cooled children with mammillary body abnormalities at school‐age have reduced cognitive scores, smaller hippocampi, and altered MTT microstructure compared with those without mammillary body abnormalities, and matched controls. What this paper adds: Cooled children are at higher risk of mammillary body abnormalities than controls.Abnormal mammillary bodies are associated with reduced cognitive scores and smaller hippocampi.Abnormal mammillary bodies are associated with altered mammillothalamic tract diffusivity. [ABSTRACT FROM AUTHOR]

The primary aim of this study is to examine whether bursting interhemispheric synchrony (bIHS) in the first week of life of infants born extremely preterm, is associated with microstructural development of the corpus callosum (CC) on term equivalent age magnetic resonance imaging scans. The secondary aim is to address the effects of analgesics such as morphine, on bIHS in extremely preterm infants. A total of 25 extremely preterm infants (gestational age [GA] < 28 weeks) were monitored with the continuous two‐channel EEG during the first 72 h and after 1 week from birth. bIHS was analyzed using the activation synchrony index (ASI) algorithm. Microstructural development of the CC was assessed at ~ 30 and ~ 40 weeks of postmenstrual age (PMA) using fractional anisotropy (FA) measurements. Multivariable regression analyses were used to assess the primary and secondary aim. Analyses were adjusted for important clinical confounders: morphine, birth weight z‐score, and white matter injury score. Due to the reduced sample size, only the most relevant variables, according to literature, were included. ASI was not significantly associated with FA of the CC at 30 weeks PMA and at 40 weeks PMA (p >.5). ASI was positively associated with the administration of morphine (p <.05). Early cortical synchrony may be affected by morphine and is not associated with the microstructural development of the CC. More studies are needed to evaluate the long‐term effects of neonatal morphine treatment to optimize sedation in this high‐risk population. [ABSTRACT FROM AUTHOR]

Introduction: The brain magnetic resonance imaging (MRI) result is a major predictor for the outcome of term infants with perinatal asphyxia who underwent therapeutic hypothermia. In daily practice, no uniform method is used to assess these images. Purpose: The aim of this study was to determine which MRI-score best predicts adverse outcome at 24 months of age and has the highest inter-rater reliability. Methods: Four MRI scoring systems for term infants with perinatal asphyxia were selected: Rutherford score, Trivedi score, Weeke score, and NICHD NRN score. Experienced blinded raters retrospectively evaluated the brain MR Images of 161 infants using all four scoring systems. Long-term outcome (the composite outcome death or adverse outcome, and its separate components) were routinely assessed by standardized testing at the age of 24 months. The predictive accuracy was assessed by logistic regression analyses and expressed as area under the ROC curve (AUC). The inter-rater reliability of the scores was calculated by the weighted Kappa or intraclass correlation. A sensitivity analysis using only high-quality MRI scans was performed. Results: All four MRI scoring systems demonstrated an AUC of >0.66 for the prediction of adverse outcome and ≥0.80 for the prediction of death. The inter-rater reliability analyses demonstrated the highest reliability for the Weeke and Trivedi scores. When only assessing the high-quality scans, the AUC increased further. Conclusion: All four MRI brain scores proved reliable predictors for an adverse outcome at 24 months of age. The Weeke and Trivedi score demonstrated the highest inter-rater reliability. The use of high-quality MRI further improved prediction. [ABSTRACT FROM AUTHOR]

Hypoxic-ischemic encephalopathy (HIE) is a major cause of neurological sequelae in (near-)term newborns. Despite the use of therapeutic hypothermia, a significant number of newborns still experience impaired neurodevelopment. Neuroimaging is the standard of care in infants with HIE to determine the timing and nature of the injury, guide further treatment decisions, and predict neurodevelopmental outcomes. Cranial ultrasonography is a helpful noninvasive tool to assess the brain before initiation of hypothermia to look for abnormalities suggestive of HIE mimics or antenatal onset of injury. Magnetic resonance imaging (MRI) which includes diffusion-weighted imaging has, however, become the gold standard to assess brain injury in infants with HIE, and has an excellent prognostic utility. Magnetic resonance spectroscopy provides complementary metabolic information and has also been shown to be a reliable prognostic biomarker. Advanced imaging modalities, including diffusion tensor imaging and arterial spin labeling, are increasingly being used to gain further information about the etiology and prognosis of brain injury. Over the past decades, tremendous progress has been made in the field of neonatal neuroimaging. In this review, the main brain injury patterns of infants with HIE, the application of conventional and advanced MRI techniques in these newborns, and HIE mimics, will be described. [ABSTRACT FROM AUTHOR]