Publications by authors named "Jeroen Dudink"

78 Publications

The relationship between preterm birth and sleep in children at school age: A systematic review.

Sleep Med Rev 2021 Jan 26;57:101447. Epub 2021 Jan 26.

Department of Neonatology, University Medical Center Utrecht, Utrecht, the Netherlands; Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands. Electronic address:

Premature birth (before 37 weeks of gestation) has been linked to a variety of adverse neurological outcomes. Sleep problems are associated with decreased neurocognitive functioning, which is especially common in children born preterm. The exact relationship between prematurity and sleep at school age is unknown. A systematic review is performed with the aim to assess the relationship between prematurity and sleep at school age (5th to 18th year of life), in comparison to sleep of their peers born full-term. Of 347 possibly eligible studies, nine were included. The overall conclusion is that prematurity is associated with earlier bedtimes and a lower sleep quality, in particular more nocturnal awakenings and more non-rapid eye movement stage 2 sleep. Interpretations and limitations of the review are discussed. Moreover, suggestions for future research are brought forward, including the need for a systematic approach with consistent outcome measures in this field of research. A better understanding of the mechanisms that influence sleep in the vulnerable group of children born preterm could help optimize these children's behavioral and intellectual development.
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http://dx.doi.org/10.1016/j.smrv.2021.101447DOI Listing
January 2021

Pathophysiology of Cerebral Hyperperfusion in Term Neonates With Hypoxic-Ischemic Encephalopathy: A Systematic Review for Future Research.

Front Pediatr 2021 2;9:631258. Epub 2021 Feb 2.

Department of Neonatology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.

Worldwide neonatal hypoxic-ischemic encephalopathy (HIE) is a common cause of mortality and neurologic disability, despite the implementation of therapeutic hypothermia treatment. Advances toward new neuroprotective interventions have been limited by incomplete knowledge about secondary injurious processes such as cerebral hyperperfusion commonly observed during the first 1-5 days after asphyxia. Cerebral hyperperfusion is correlated with adverse neurodevelopmental outcome and it is a process that remains poorly understood. In order to provide an overview of the existing knowledge on the pathophysiology and highlight the gaps in current understanding of cerebral hyperperfusion in term animals and neonates with HIE, we performed a systematic research. We included papers scoping for study design, population, number of participants, study technique and relevant findings. Methodological quality was assessed using the checklist for cohort studies from The Joanna Briggs Institute. Out of 2,690 results, 34 studies were included in the final review-all prospective cohort studies. There were 14 studies of high, 17 moderate and 3 of low methodological quality. Data from the literature were analyzed in two main subjects: (1) Hemodynamic Changes subdivided into macro- and microscopic hemodynamic changes, and (2) Endogenous Pathways which was subdivided into N-methyl-D-aspartate/Mitogen activated protein kinase (NDMA/MAPK), Nitric Oxide (NO), prostanoids and other endogenous studies. Cerebral hyperperfusion in term neonates with HIE was found to be present 10-30 min after the hypoxic-ischemic event and was still present around day 10 and up to 1 month after birth. Cerebral hyperperfusion was also characterized by angiogenesis and cerebral vasodilation. Additionally, cerebral vasodilation was mediated by endogenous pathways such as MAPK through urokinase Plasminogen Activator (uPA), by neuronal NO synthase following NMDA and by prostanoid synthesis. Future research should elucidate the precise role of NMDA, MAPK and prostanoids in cerebral hyperperfusion. Moreover, research should focus on possible interventions and the effect of hypothermia on hyperperfusion. These findings should be taken into account simultaneously with brain imagining techniques, becoming a valuable asset in assessing the impact in neurodevelopmental outcome.
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http://dx.doi.org/10.3389/fped.2021.631258DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884860PMC
February 2021

Cerebellar volumes and language functions in school-aged children born very preterm.

Pediatr Res 2021 Jan 19. Epub 2021 Jan 19.

Division of Neonatology, Department of Pediatrics at UMCU-Wilhelmina Children's Hospital, Utrecht, Netherlands.

Background: Volumes of cerebellar posterior lobes have been associated with cognitive skills, such as language functioning. Children born very preterm (VPT) often have language problems. However, only total cerebellar volume has been associated with language functioning, with contradicting results. The objective of this study was to ascertain whether total cerebellar structures or specific posterior lobular structures are associated with language ability of school-aged VPT children.

Methods: This is a prospective cohort study of 42 school-aged VPT children without major handicaps. Structural MRI was performed and the cerebellum segmentation pipeline was used for segmentation of separate lobules. Narrative retelling assessment was performed and language content and language structure scores were extracted. Linear regression analyses were used to associate language scores with whole gray matter (GM) cerebellar volume and right Crus I+II GM volume.

Results: Whole cerebellar GM volume was not significantly associated with language content nor with language structure; however, right Crus I+II GM volume was significantly associated with language content (β = 0.192 (CI = 0.033, 0.351), p = 0.020).

Conclusions: GM volume of Crus I+II appears to be associated with language functions in school-aged VPT children without major handicaps, while whole cerebellar volume is not. This study showed the importance of studying cerebellar lobules separately, rather than whole cerebellar volume only, in relation to VPT children's language functions.

Impact: GM volume of Crus I+II is associated with semantic language functions in school-aged very preterm children without overt brain injury, whereas whole cerebellar volume is not. This study showed the importance of studying cerebellar lobules separately, rather than whole cerebellar volume only, in relation to very preterm children's language functions. This study might impact future research in very preterm children. Lobular structures rather than whole cerebellar structures should be the region of interest in relation to language functions.
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http://dx.doi.org/10.1038/s41390-020-01327-zDOI Listing
January 2021

Performing newborn life support in advance of neonatal advanced life support course-back to basics?

Eur J Pediatr 2021 Jan 13. Epub 2021 Jan 13.

Division of Neonatology, Department of Paediatrics, Amalia Children's Hospital, Radboud Institute for Health Sciences, Radboud University Medical Centre, Geert Grooteplein Zuid 10, 6525 GA, Nijmegen, The Netherlands.

In this retrospective analysis, the Newborn Life Support (NLS) test scenario performance of participants of the Dutch Neonatal Advanced Life Support (NALS) course was assessed. Characteristics of participants and total amount of failures were collected. Failures were subdivided in (1) errors of omission; (2) errors of commission; and (3) unspecified if data was missing. Pearson's chi-squared test was used to assess differences between participant groups. In total, 23 out of 86 participants (27%) failed their NLS test scenario. Life support course instructors in general (20/21) passed their test scenario more often compared to other participants (43/65) (p = 0.008). In total 110 fail items were recorded; the most common errors being not assessing heart rate (error of omission) (n = 47) and inadequate performance of airway management (error of commission) (n = 24).Conclusion: A substantial part of NALS participants failed their NLS test scenario. Errors of omission could be reduced by the availability of a checklist/NLS algorithm. Life support course instructors possibly make less errors of commission due to retention of skills by teaching these skills at least twice a year. Therefore, our study suggests that neonatal basic life support skills should be retained by local assurance of training programmes. What is Known: • Retention of skills after life support courses decreases after three months. • Adherence to newborn life support guidelines is suboptimal. What is New: • NLS performance is suboptimal in participants for advanced neonatal life support. • Most common failures are not assessing heart rate and inadequate airway management.
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http://dx.doi.org/10.1007/s00431-020-03917-9DOI Listing
January 2021

Synthetic MRI demonstrates prolonged regional relaxation times in the brain of preterm born neonates with severe postnatal morbidity.

Neuroimage Clin 2021 24;29:102544. Epub 2020 Dec 24.

Department of Radiology, Vrije Universiteit Brussel, Universitair Ziekenhuis Brussel, Brussels, Belgium.

Background: To identify preterm infants at risk for neurodevelopment impairment that might benefit from early neurorehabilitation, early prognostic biomarkers of future outcomes are needed.

Objective: To determine whether synthetic MRI is sensitive to age-related changes in regional tissue relaxation times in the brain of preterm born neonates when scanned at term equivalent age (TEA, 37-42 weeks), and to investigate whether severe postnatal morbidity results in prolonged regional tissue relaxation times.

Materials And Methods: This retrospective study included 70 very preterm born infants scanned with conventional and synthetic MRI between January 2017 and June 2019 at TEA. Infants with severe postnatal morbidity were allocated to a high-risk group (n = 22). All other neonates were allocated to a low-risk group (n = 48). Linear regression analysis was performed to determine the relationship between relaxation times and postmenstrual age (PMA) at scan. Analysis of covariance was used to evaluate the impact of severe postnatal morbidity in the high-risk group on T1 and T2 relaxation times. Receiver operating characteristic (ROC) curves were plotted and analysed with area under the ROC curve (AUC) to evaluate the accuracy of classifying high-risk patients based on regional relaxation times.

Results: A linear age-related decrease of T1 and T2 relaxation times correlating with PMA at scan (between 37 and 42 weeks) was found in the deep gray matter, the cerebellum, the cortex, and the posterior limb of the internal capsule (PLIC) (p < .005 each), but not in the global, frontal, parietal, or central white matter. Analysis of covariance for both risk groups, adjusted for PMA, revealed significantly prolonged regional tissue relaxation times in neonates with severe postnatal morbidity, which was best illustrated in the central white matter of the centrum semiovale (T1 Δ = 11.5%, T2 Δ = 13.4%, p < .001) and in the PLIC (T1 Δ = 9.2%, T2 Δ = 6.9%, p < .001). The relaxation times in the PLIC and the central white matter predicted high-risk status with excellent accuracy (AUC range 0.82-0.86).

Conclusion: Synthetic MRI-based relaxometry in the brain of preterm born neonates is sensitive to age-related maturational changes close to TEA. Severe postnatal morbidity correlated with a significant delay in tissue relaxation. Synthetic MRI may provide early prognostic biomarkers for neurodevelopment impairment.
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http://dx.doi.org/10.1016/j.nicl.2020.102544DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7786121PMC
December 2020

Systemic multipotent adult progenitor cells protect the cerebellum after asphyxia in fetal sheep.

Stem Cells Transl Med 2021 Jan 28;10(1):57-67. Epub 2020 Sep 28.

Department of Pediatrics, Maastricht University Medical Centre, Maastricht, The Netherlands.

Involvement of the cerebellum in the pathophysiology of hypoxic-ischemic encephalopathy (HIE) in preterm infants is increasingly recognized. We aimed to assess the neuroprotective potential of intravenously administered multipotent adult progenitor cells (MAPCs) in the preterm cerebellum. Instrumented preterm ovine fetuses were subjected to transient global hypoxia-ischemia (HI) by 25 minutes of umbilical cord occlusion at 0.7 of gestation. After reperfusion, two doses of MAPCs were administered intravenously. MAPCs are a plastic adherent bone-marrow-derived population of adult progenitor cells with neuroprotective potency in experimental and clinical studies. Global HI caused marked cortical injury in the cerebellum, histologically indicated by disruption of cortical strata, impeded Purkinje cell development, and decreased dendritic arborization. Furthermore, global HI induced histopathological microgliosis, hypomyelination, and disruption of white matter organization. MAPC treatment significantly prevented cortical injury and region-specifically attenuated white matter injury in the cerebellum following global HI. Diffusion tensor imaging (DTI) detected HI-induced injury and MAPC neuroprotection in the preterm cerebellum. This study has demonstrated in a preclinical large animal model that early systemic MAPC therapy improved structural injury of the preterm cerebellum following global HI. Microstructural improvement was detectable with DTI. These findings support the potential of MAPC therapy for the treatment of HIE and the added clinical value of DTI for the detection of cerebellar injury and the evaluation of cell-based therapy.
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http://dx.doi.org/10.1002/sctm.19-0157DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780812PMC
January 2021

Cerebellar injury in term neonates with hypoxic-ischemic encephalopathy is underestimated.

Pediatr Res 2020 Sep 23. Epub 2020 Sep 23.

Department of Neonatology, Wilhelmina Children's Hospital, University Medical Center Utrecht Brain Center, University Utrecht, Utrecht, The Netherlands.

Background: Postmortem examinations frequently show cerebellar injury in infants with severe hypoxic-ischemic encephalopathy (HIE), while it is less well visible on MRI. The primary aim was to investigate the correlation between cerebellar apparent diffusion coefficient (ADC) values and histopathology in infants with HIE. The secondary aim was to compare ADC values in the cerebellum of infants with HIE and infants without brain injury.

Methods: ADC values in the cerebellar vermis, hemispheres and dentate nucleus (DN) of (near-)term infants with HIE (n = 33) within the first week after birth were compared with neonates with congenital non-cardiac anomalies, normal postoperative MRIs and normal outcome (n = 22). Microglia/macrophage activation was assessed using CD68 and/or HLA-DR staining and Purkinje cell (PC) injury using H&E-stained slices. The correlation between ADC values and the histopathological measures was analyzed.

Results: ADC values in the vermis (p = 0.021) and DN (p < 0.001) were significantly lower in infants with HIE compared to controls. ADC values in the cerebellar hemispheres were comparable. ADC values in the vermis were correlated with the number and percentage of normal PCs; otherwise ADC values and histology were not correlated.

Conclusion: Histopathological injury in the cerebellum is common in infants with HIE. ADC values underestimate histopathological injury.

Impact: ADC values might underestimate cerebellar injury in neonates with HIE. ADC values in the vermis and dentate nucleus of infants with HIE are lower compared to controls, but not in the cerebellar hemispheres. Abnormal ADC values are only found when cytotoxic edema is very severe. ADC values in the vermis are correlated with Purkinje cell injury in the vermis; furthermore, there were no correlations between ADC values and histopathological measures.
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http://dx.doi.org/10.1038/s41390-020-01173-zDOI Listing
September 2020

24-hour activity for children with cerebral palsy: a clinical practice guide.

Dev Med Child Neurol 2021 Jan 27;63(1):54-59. Epub 2020 Aug 27.

CanChild Centre for Childhood Disability Research, Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada.

The association between physical activity and health has been clearly established, and the promotion of physical activity should be viewed as a cost-effective approach that is universally prescribed as a first-line treatment for nearly every chronic disease. Health care providers involved in the care for individuals with cerebral palsy (CP) are encouraged to take an active role in promoting their health and well-being. Balancing activity behaviours across the whole day, with improved physical activity, reduced sedentary time, and healthy sleep behaviours, can set up infants, preschool-, and school-aged children with CP for a healthy trajectory across their lifetime. However, most clinicians do not apply a systematic surveillance, assessment, and management approach to detect problems with physical activity or sleep in children with CP. Consequently, many children with CP miss out on an important first line of treatment. This article presents an evidence-informed clinical practice guide with practical pointers to help practitioners in detecting 24-hour activity problems as a critical step towards adoption of healthy lifestyle behaviours for children with CP that provide long-term health benefits.
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http://dx.doi.org/10.1111/dmcn.14654DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7754464PMC
January 2021

The developing brain by trimester.

Handb Clin Neurol 2020 ;171:245-289

Department of Neonatology, University Medical Center, Utrecht, The Netherlands.

Transient anatomical entities play a role in the maturation of brain regions and early functional fetal networks. At the postmenstrual age of 7 weeks, major subdivisions of the brain are visible. At the end of the embryonic period, the cortical plate covers the neopallium. The choroid plexus develops in concert with it, and the dorsal thalamus covers about half the diencephalic third ventricle surface. In addition to the fourth ventricle neuroepithelium the rhombic lips are an active neuroepithelial production site. Early reciprocal connections between the thalamus and cortex are present. The corticospinal tract has reached the pyramidal decussation, and the arteries forming the mature circle of Willis are seen. Moreover, the superior sagittal sinus has formed, and at the rostral neuropore the massa commissuralis is growing. At the viable preterm age of around 24 weeks PMA, white matter tracts are in full development. Asymmetric progenitor division permits production of neurons, subventricular zone precursors, and glial cells. Myelin is present in the ventral spinal quadrant, cuneate fascicle, and spinal motor fibers. The neopallial mantle has been separated into transient layers (stratified transitional fields) between the neuroepithelium and the cortical plate. The subplate plays an important role in organizing the structuring of the cortical plate. Commissural tracts have shaped the corpus callosum, early primary gyri are present, and opercularization has started caudally, forming the lateral fissure. Thalamic and striatal nuclei have formed, although GABAergic neurons continue to migrate into the thalamus from the corpus gangliothalamicum. Near-term PMA cerebral sublobulation is active. Between 24 and 32 weeks, primary sulci develop. Myelin is present in the superior cerebellar peduncle, rubrospinal tract, and inferior olive. Germinal matrix disappears from the telencephalon, except for the GABAergic frontal cortical subventricular neuroepithelium.
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http://dx.doi.org/10.1016/B978-0-444-64239-4.00014-XDOI Listing
January 2020

Current ideas about the roles of rapid eye movement and non-rapid eye movement sleep in brain development.

Acta Paediatr 2021 01 8;110(1):36-44. Epub 2020 Aug 8.

Department of Neonatology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands.

Understanding the links between sleep and brain development is important, as rapid eye movement (REM) sleep and non-REM (NREM) sleep seem to contribute to different aspects of brain maturation. If children have sleep problems, REM sleep and NREM sleep are likely to have different consequences for their developing brain, depending on their age. We highlight important discoveries from human and animal research on the role sleep plays in brain development. A hypothetical model is presented to explain the dynamic relationship of REM sleep and NREM sleep with different processes of brain maturation, with implications for current neonatal care and future research.
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http://dx.doi.org/10.1111/apa.15485DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7818400PMC
January 2021

Non-right-handedness in children born extremely preterm: Relation to early neuroimaging and long-term neurodevelopment.

PLoS One 2020 6;15(7):e0235311. Epub 2020 Jul 6.

Department of Neonatology, Wilhelmina Children's Hospital, University Medical Centre Utrecht, Utrecht University, Utrecht, The Netherlands.

Objective: This study aimed to define the prevalence and predictors of non-right-handedness and its link to long-term neurodevelopmental outcome and early neuroimaging in a cohort of children born extremely preterm (<28 weeks gestation).

Methods: 179 children born extremely preterm admitted to the Neonatal Intensive Care Unit of our tertiary centre from 2006-2013 were included in a prospective longitudinal cohort study. Collected data included perinatal data, demographic characteristics, neurodevelopmental outcome measured by the Bayley Scales of Infant and Toddler Development at 2 years and the Movement Assessment Battery for Children at 5 years, and handedness measured at school age (4-8 years). Magnetic resonance imaging performed at term-equivalent age was used to study overt brain injury. Diffusion tensor imaging scans were analysed using tract-based spatial statistics to assess white matter microstructure in relation to handedness and neurodevelopmental outcome.

Results: The prevalence of non-right-handedness in our cohort was 22.9%, compared to 12% in the general population. Weaker fine motor skills at 2 years and paternal non-right-handedness were significantly associated with non-right-handedness. Both overt brain injury and fractional anisotropy of white matter structures on diffusion tensor images were not related to handedness. Fractional anisotropy measurements showed significant associations with neurodevelopmental outcome.

Conclusions: Our data show that non-right-handedness in children born extremely preterm occurs almost twice as frequently as in the general population. In the studied population, non-right-handedness is associated with weaker fine motor skills and paternal non-right-handedness, but not with overt brain injury or microstructural brain development on early magnetic resonance imaging.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0235311PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7337339PMC
September 2020

Brain Damage and Visuospatial Impairments: Exploring Early Structure-Function Associations in Children Born Very Preterm.

Pediatr Neurol 2020 08 28;109:63-71. Epub 2020 Jan 28.

Vestibular and Oculomotor Research Group, Department of Neuroscience, Erasmus Medical Center, Rotterdam, the Netherlands. Electronic address:

Background: To provide insight into early neurosensory development in children born very preterm, we assessed the association between early structural brain damage and functional visuospatial attention and motion processing from one to two years corrected age.

Methods: In 112 children born at less than 32 weeks gestational age, we assessed brain damage and growth with a standardized scoring system on magnetic resonance imaging (MRI; 1.5 Tesla) scans performed at 29 to 35 weeks gestational age. Of the children with an MRI scan, 82 participated in an eye tracking-based assessment of visuospatial attention and motion processing (Tobii T60XL) at one year corrected age and 59 at two years corrected age.

Results: MRI scoring showed good intra- and inter-rater reproducibility. At one year, 10% children had delayed attentional reaction times and 23% had delayed motion reaction times. Moderate to severe brain damage significantly correlated with slower visuospatial reaction times. At two years, despite attention and motion reaction times becoming significantly faster, 20% had delayed attentional reaction times and 35% had delayed motion reaction times, but no correlations with MRI scores were found. The presence of structural brain damage was associated with abnormal functional performance over age.

Conclusions: The present study indicates an association between moderate to severe brain damage and visuospatial attention and motion processing dysfunction at one year corrected age. This provides a new perspective on comprehensive MRI scoring and quantitative functional visuospatial assessments and their applicability in children born very preterm in their first years of life.
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http://dx.doi.org/10.1016/j.pediatrneurol.2019.12.010DOI Listing
August 2020

Predictors of Outcomes in Hypoxic-Ischemic Encephalopathy following Hypothermia: A Meta-Analysis.

Neonatology 2020 1;117(4):411-427. Epub 2020 Apr 1.

Department of Neonatology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands.

Introduction: Prediction of neurodevelopmental outcome in infants with hypoxic-ischemic encephalopathy remains an important challenge. Various studies have shown that the predictive ability of different modalities changed after the introduction of therapeutic hypothermia. This paper reviews the diagnostic test accuracy of the different modalities that are being used to predict neurodevelopmental outcomes following therapeutic hypothermia.

Methods: A systematic literature search was performed using Embase and PubMed. Two reviewers independently included eligible studies and extracted data. The quality of the studies was assessed using the Quality in Prognosis Studies Tool. Meta-analyses were performed where possible.

Results: Forty-seven articles and 3 conference abstracts were included, reporting on 3,072infants of whom 39% died or had an adverse neurodevelopmental outcome. A meta-analysis could be performed using 37 articles on (amplitude-integrated) electroencephalography (EEG), conventional magnetic resonance imaging (MRI), diffusion-weighted imaging (DWI), and proton magnetic resonance spectroscopy (1H-MRS). Amplitude-integrated EEG (aEEG) at 24 and 72 h showed similar high diagnostic OR, while aEEG at 6 h and EEG performed less, both due to a low specificity. For MRI, most studies reported scoring systems in which early (<8 days) MRI performed better than late (≥8 days) MRI. Injury to the posterior limb of the internal capsule on MRI or to the thalami on DWI were strong individual predictors, as was an increased lactate/N-acetylaspartate peak on 1H-MRS.

Conclusions: In the era of therapeutic hypothermia, the different modalities remain good predictors of neurodevelopmental outcome. However, timing should be taken into account. aEEG may initially be false positive and gets more reliable after 24 h. In contrast, MRI should be used during the first week, as its predictive value decreases afterwards.
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http://dx.doi.org/10.1159/000505519DOI Listing
April 2020

State-of-the-art neonatal cerebral ultrasound: technique and reporting.

Pediatr Res 2020 03;87(Suppl 1):3-12

Department of Neonatology, Helios Klinikum Berlin Buch, Berlin, Germany.

In the past three decades, cerebral ultrasound (CUS) has become a trusted technique to study the neonatal brain. It is a relatively cheap, non-invasive, bedside neuroimaging method available in nearly every hospital. Traditionally, CUS was used to detect major abnormalities, such as intraventricular hemorrhage (IVH), periventricular hemorrhagic infarction, post-hemorrhagic ventricular dilatation, and (cystic) periventricular leukomalacia (cPVL). The use of different acoustic windows, such as the mastoid and posterior fontanel, and ongoing technological developments, allows for recognizing other lesion patterns (e.g., cerebellar hemorrhage, perforator stroke, developmental venous anomaly). The CUS technique is still being improved with the use of higher transducer frequencies (7.5-18 MHz), 3D applications, advances in vascular imaging (e.g. ultrafast plane wave imaging), and improved B-mode image processing. Nevertheless, the helpfulness of CUS still highly depends on observer skills, knowledge, and experience. In this special article, we discuss how to perform a dedicated state-of-the-art neonatal CUS, and we provide suggestions for structured reporting and quality assessment.
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http://dx.doi.org/10.1038/s41390-020-0776-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7098885PMC
March 2020

The development and validation of a cerebral ultrasound scoring system for infants with hypoxic-ischaemic encephalopathy.

Pediatr Res 2020 03;87(Suppl 1):59-66

Department of Neonatology, Wilhelmina Children's Hospital, University Medical Centre Utrecht, Utrecht University, Utrecht, the Netherlands.

Background: Hypoxic-ischaemic encephalopathy (HIE) is an important cause of morbidity and mortality in neonates. When the gold standard MRI is not feasible, cerebral ultrasound (CUS) might offer an alternative. In this study, the association between a novel CUS scoring system and neurodevelopmental outcome in neonates with HIE was assessed.

Methods: (Near-)term infants with HIE and therapeutic hypothermia, a CUS on day 1 and day 3-7 after birth and available outcome data were retrospectively included in cohort I. CUS findings on day 1 and day 3-7 were related to adverse outcome in univariate and the CUS of day 3-7 also in multivariable logistic regression analyses. The resistance index, the sum of deep grey matter and of white matter involvement were included in multivariable logistic regression analyses. A comparable cohort from another hospital was used for validation (cohort II).

Results: Eighty-three infants were included in cohort I and 35 in cohort II. The final CUS scoring system contained the sum of white matter (OR = 2.6, 95% CI 1.5-4.7) and deep grey matter involvement (OR = 2.7, 95% CI 1.7-4.4). The CUS scoring system performed well in cohort I (AUC = 0.90) and II (AUC = 0.89).

Conclusion: This validated CUS scoring system is associated with neurodevelopmental outcome in neonates with HIE.
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http://dx.doi.org/10.1038/s41390-020-0782-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7098882PMC
March 2020

Diagnostic and predictive value of Doppler ultrasound for evaluation of the brain circulation in preterm infants: a systematic review.

Pediatr Res 2020 03;87(Suppl 1):50-58

Department of Neonatology, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium.

Introduction: Very and extremely preterm infants frequently have brain injury-related long-term neurodevelopmental problems. Altered perfusion, for example, seen in the context of a hemodynamically significant patent ductus arteriosus (PDA), has been linked to injury of the immature brain. However, a direct relation with outcome has not been reviewed systematically.

Methods: A systematic review was conducted to provide an overview of the value of different cerebral arterial blood flow parameters assessed by Doppler ultrasound, in relation to brain injury, to predict long-term neurodevelopmental outcome in preterm infants.

Results: In total, 23 studies were included. Because of heterogeneity of studies, a meta-analysis of results was not possible. All included studies on resistance index (RI) showed significantly higher values in subjects with a hemodynamically significant PDA. However, absolute differences in RI values were small. Studies using Doppler parameters to predict brain injury and long-term neurodevelopmental outcome were inconsistent.

Discussion: There is no clear evidence to support the routine determination of RI or other Doppler parameters in the cerebral arteries to predict brain injury and long-term neurodevelopmental outcome in the preterm infant. However, there is evidence that elevated RI can point to the presence of a hemodynamically significant PDA.
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http://dx.doi.org/10.1038/s41390-020-0777-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7098887PMC
March 2020

Preterm infants with isolated cerebellar hemorrhage show bilateral cortical alterations at term equivalent age.

Sci Rep 2020 03 24;10(1):5283. Epub 2020 Mar 24.

Department of Neonatology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.

The cerebellum is connected to numerous regions of the contralateral side of the cerebrum. Motor and cognitive deficits following neonatal cerebellar hemorrhages (CbH) in extremely preterm neonates may be related to remote cortical alterations, following disrupted cerebello-cerebral connectivity as was previously shown within six CbH infants. In this retrospective case series study, we used MRI and advanced surface-based analyses to reconstruct gray matter (GM) changes in cortical thickness and cortical surface area in extremely preterm neonates (median age = 26; range: 24.9-26.7 gestational weeks) with large isolated unilateral CbH (N = 5 patients). Each CbH infant was matched with their own preterm infant cohort (range: 20-36 infants) based on sex and gestational age at birth. On a macro level, our data revealed that the contralateral cerebral hemisphere of CbH neonates did not show less cortical thickness or cortical surface area than their ipsilateral cerebral hemisphere at term. None of the cases differed from their matched cohort groups in average cortical thickness or average cortical surface area in the ipsilateral or contralateral cerebral hemisphere. On a micro (i.e. vertex) level, we established high variability in significant local cortical GM alteration patterns across case-cohort groups, in which the cases showed thicker or bigger volume in some regions, among which the caudal middle frontal gyrus, insula and parahippocampal gyrus, and thinner or less volume in other regions, among which the cuneus, precuneus and supratentorial gyrus. This study highlights that cerebellar injury during postnatal stages may have  widespread bilateral influence on the early maturation of cerebral cortical regions, which implicate complex cerebello-cerebral interactions to be present at term birth.
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http://dx.doi.org/10.1038/s41598-020-62078-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7093404PMC
March 2020

Language functions deserve more attention in follow-up of children born very preterm.

Eur J Paediatr Neurol 2020 May 14;26:75-81. Epub 2020 Feb 14.

Department of Otorhinolaryngology at Erasmus Medical University Centre-Sophia Children's Hospital, Rotterdam, Netherlands.

Background: Language is a complex neurodevelopmental phenomenon. Approximately 45% of children born very preterm (VP) show mild-to-severe language problems throughout childhood. Nevertheless, in most hospitals in Europe language functions are not routinely assessed at follow-up.

Objective: To give clear indications for extensive language assessment in school-aged children born VP, based on routinely assessed intelligence and behavioral problems.

Method: Language functions of 63 10-year-old children born VP (<32 weeks' gestation) without major handicaps were compared to their intellectual and executive functions and behavioral problems. Using multiple linear regression analyses, the predictive value of perinatal factors and the association with neurodevelopmental factors of low language were measured.

Results: The mean language score was significantly lower than the verbal intelligent quotient (VIQ; mean difference = 6.4, p < .001, d=.48) and the mean vocabulary knowledge (mean difference = 9.3, p < .001, d=.70). Besides, VIQ (β = .649, p = .001) and performance IQ (PIQ; β = .260, p = .035) were significantly associated with language scores. Significant predictors of language scores were number of days of assisted ventilation (β = -.592, p = .015) and mother's vocabulary knowledge (β =.473, p = .014), rather than mother's educational level (β =.139, p = .956).

Conclusions: Children born VP had language problems that were not expected from their significantly higher VIQ and vocabulary knowledge. Clinicians assessing these children should be aware of possible language problems, which cannot be detected with a simple vocabulary task. Our findings provide evidence of the need for adequate language assessments by a speech-language pathologist in children born VP, especially in those with VIQ scores in the low average range.
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http://dx.doi.org/10.1016/j.ejpn.2020.02.004DOI Listing
May 2020

Does a narrative retelling task improve the assessment of language proficiency in school-aged children born very preterm?

Clin Linguist Phon 2020 Dec 3;34(12):1112-1129. Epub 2020 Feb 3.

Department of Otorhinolaryngology, Erasmus Medical University Centre-Sophia Children's Hospital , Rotterdam, Netherlands.

Almost half of the children born very preterm (VP) experience language difficulties at school-age, specifically with more complex language tasks. Narrative retelling is such a task. Therefore, we explored the value of narrative retelling assessment in school-aged children born VP, compared to item-based language assessment. In 63 children born VP and 30 age-matched full-term (FT) controls Renfrew's Bus Story Test and Clinical Evaluation of Language Fundamentals were assessed. The retelling of the Bus Story was transcribed and language complexity and content measures were analyzed with Computerised Language Analysis software. Narrative outcomes of the VP group were worse than that of the FT group. Group differences were significant for the language complexity measures, but not for the language content measures. However, the mean narrative composite score of the VP group was significantly than their mean item-based language score, while in the FT group the narrative score was than the item-based score. Significant positive correlations between narrative and item-based language scores were found only in the VP group. In conclusion, in VP children narrative retelling appears to be less sensitive to detecting academic language problems than item-based language assessment. This might be related to the mediating role of attention in item-based tasks, that appears not to affect more spontaneous language tasks such as retelling. Therefore, in school-aged children born VP we recommend using narrative assessment, in addition to item-based assessments, because it is more related to spontaneous language and less sensitive to attention problems.
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http://dx.doi.org/10.1080/02699206.2020.1720824DOI Listing
December 2020

Brain temperature of infants with neonatal encephalopathy following perinatal asphyxia calculated using magnetic resonance spectroscopy.

Pediatr Res 2020 08 2;88(2):279-284. Epub 2020 Jan 2.

Department of Radiology, University Medical Center Utrecht, University Utrecht, Utrecht, The Netherlands.

Background: Little is known about brain temperature of neonates during MRI. Brain temperature can be estimated non-invasively with proton Magnetic Resonance Spectroscopy (H-MRS), but the most accurate H-MRS method has not yet been determined. The primary aim was to estimate brain temperature using H-MRS in infants with neonatal encephalopathy (NE) following perinatal asphyxia. The secondary aim was to compare brain temperature during MRI with rectal temperatures before and after MRI.

Methods: In this retrospective study, brain temperature in 36 (near-)term infants with NE was estimated using short (36 ms) and long (288 ms) echo time (TE) H-MRS. Brain temperature was calculated using two different formulas: formula of Wu et al. and a formula based on phantom calibration. The methods were compared. Rectal temperatures were collected <3 hours before and after MRI.

Results: Brain temperatures calculated with the formula of Wu et al. and the calibrated formula were similar as well as brain temperatures derived from short and long TE H-MRS. Rectal temperature did not differ before and after MRI.

Conclusions: Brain temperature can be measured using H-MRS in daily clinical practice using the formula of Wu et al. with both short and long TE H-MRS. Brain temperature remained within physiological range during MRI.
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http://dx.doi.org/10.1038/s41390-019-0739-3DOI Listing
August 2020

Two-dimensional ultrasound measurements vs. magnetic resonance imaging-derived ventricular volume of preterm infants with germinal matrix intraventricular haemorrhage.

Pediatr Radiol 2020 02 6;50(2):234-241. Epub 2019 Nov 6.

Department of Neonatology, Wilhelmina Children's Hospital/University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.

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 = 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.
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http://dx.doi.org/10.1007/s00247-019-04542-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6978291PMC
February 2020

Brain Activity and Cerebral Oxygenation After Perinatal Arterial Ischemic Stroke Are Associated With Neurodevelopment.

Stroke 2019 10 8;50(10):2668-2676. Epub 2019 Aug 8.

From the Department of Neonatology, University Medical Center Utrecht (N.W., D.J.M.v.d.B., P.M.A.L., N.E.v.d.A., J.D., F.v.B., F.G., L.S.d.V., M.J.N.L.B., T.A.), Utrecht University, the Netherlands.

Background and Purpose- In infants with perinatal arterial ischemic stroke (PAIS), early prognosis of neurodevelopmental outcome is important to adequately inform parents and caretakers. Early continuous neuromonitoring after PAIS may improve early prognosis. Our aim was to study early cerebral electrical activity and oxygenation measured by amplitude-integrated electroencephalography (aEEG) and near-infrared spectroscopy in term neonates with PAIS and relate these to the development of cerebral palsy and cognitive deficit. Methods- aEEG patterns and regional cerebral oxygen saturation (rScO) levels of both hemispheres were studied for 120 hours from the first clinical symptoms of PAIS (ie, seizures) onward. Multivariable analyses were used to investigate the association between aEEG, near-infrared spectroscopy, clinical variables, and neurodevelopmental outcome. Results- In 52 patients with PAIS (gestational age, 40.4±1.4 weeks; birth weight, 3282±479 g), median time to a continuous background pattern was longer in the ipsilesional compared with the contralesional hemisphere (13.5 versus 10.0 hours; <0.05). rScO decreased over time in both hemispheres but less in the ipsilesional one, resulting in a rScO asymmetry ratio of 4.5% (interquartile range, -4.3% to 5.9%; <0.05) between hemispheres from day 3 after symptoms onward. Both time to normal background pattern and asymmetry in rScO were negatively affected by gestational age, size of the PAIS, use of antiepileptic drugs, and mechanical ventilation. After correction for size of the PAIS on magnetic resonance imaging, a slower recovery of background pattern on ipsilesional aEEG and increased rScO asymmetry between hemispheres was related with an increased risk for cognitive deficit (<-1 SD) at a median of 24.0 (interquartile range, 18.4-24.4) months of age. Conclusions- Recovery of background pattern on aEEG and cerebral oxygenation are both affected by PAIS and related to neurocognitive development. Both measurements may provide valuable early prognostic information. Additionally, monitoring cerebral activity and oxygenation may be useful in identifying infants eligible for early neuroprotective interventions and to detect early effects of these interventions.
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http://dx.doi.org/10.1161/STROKEAHA.119.025346DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6756254PMC
October 2019

Assessment of Brain Injury and Brain Volumes after Posthemorrhagic Ventricular Dilatation: A Nested Substudy of the Randomized Controlled ELVIS Trial.

J Pediatr 2019 05 14;208:191-197.e2. Epub 2019 Mar 14.

Department of Neonatology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands; Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands. Electronic address:

Objective: To compare the effect of early and late intervention for posthemorrhagic ventricular dilatation on additional brain injury and ventricular volume using term-equivalent age-MRI.

Study Design: In the Early vs Late Ventricular Intervention Study (ELVIS) trial, 126 preterm infants ≤34 weeks of gestation with posthemorrhagic ventricular dilatation were randomized to low-threshold (ventricular index >p97 and anterior horn width >6 mm) or high-threshold (ventricular index >p97 + 4 mm and anterior horn width >10 mm) groups. In 88 of those (80%) with a term-equivalent age-MRI, the Kidokoro Global Brain Abnormality Score and the frontal and occipital horn ratio were measured. Automatic segmentation was used for volumetric analysis.

Results: The total Kidokoro score of the infants in the low-threshold group (n = 44) was lower than in the high-threshold group (n = 44; median, 8 [IQR, 5-12] vs median 12 [IQR, 9-17], respectively; P < .001). More infants in the low-threshold group had a normal or mildly increased score vs more infants in the high-threshold group with a moderately or severely increased score (46% vs 11% and 89% vs 54%, respectively; P = .002). The frontal and occipital horn ratio was lower in the low-threshold group (median, 0.42 [IQR, 0.34-0.63]) than the high-threshold group (median 0.48 [IQR, 0.37-0.68], respectively; P = .001). Ventricular cerebrospinal fluid volumes could be calculated in 47 infants and were smaller in the low-threshold group (P = .03).

Conclusions: More brain injury and larger ventricular volumes were demonstrated in the high vs the low-threshold group. These results support the positive effects of early intervention for posthemorrhagic ventricular dilatation.

Trial Registration: ISRCTN43171322.
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http://dx.doi.org/10.1016/j.jpeds.2018.12.062DOI Listing
May 2019

Pharmacokinetics of morphine in encephalopathic neonates treated with therapeutic hypothermia.

PLoS One 2019 14;14(2):e0211910. Epub 2019 Feb 14.

Department of Clinical Pharmacy, University Medical Center Utrecht, Utrecht, the Netherlands.

Objective: Morphine is a commonly used drug in encephalopathic neonates treated with therapeutic hypothermia after perinatal asphyxia. Pharmacokinetics and optimal dosing of morphine in this population are largely unknown. The objective of this study was to describe pharmacokinetics of morphine and its metabolites morphine-3-glucuronide and morphine-6-glucuronide in encephalopathic neonates treated with therapeutic hypothermia and to develop pharmacokinetics based dosing guidelines for this population.

Study Design: Term and near-term encephalopathic neonates treated with therapeutic hypothermia and receiving morphine were included in two multicenter cohort studies between 2008-2010 (SHIVER) and 2010-2014 (PharmaCool). Data were collected during hypothermia and rewarming, including blood samples for quantification of morphine and its metabolites. Parental informed consent was obtained for all participants.

Results: 244 patients (GA mean (sd) 39.8 (1.6) weeks, BW mean (sd) 3,428 (613) g, male 61.5%) were included. Morphine clearance was reduced under hypothermia (33.5°C) by 6.89%/°C (95% CI 5.37%/°C- 8.41%/°C, p<0.001) and metabolite clearance by 4.91%/°C (95% CI 3.53%/°C- 6.22%/°C, p<0.001) compared to normothermia (36.5°C). Simulations showed that a loading dose of 50 μg/kg followed by continuous infusion of 5 μg/kg/h resulted in morphine plasma concentrations in the desired range (between 10 and 40 μg/L) during hypothermia.

Conclusions: Clearance of morphine and its metabolites in neonates is affected by therapeutic hypothermia. The regimen suggested by the simulations will be sufficient in the majority of patients. However, due to the large interpatient variability a higher dose might be necessary in individual patients to achieve the desired effect.

Trial Registration: www.trialregister.nl NTR2529.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0211910PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6375702PMC
November 2019

Brain microstructural development in neonates with critical congenital heart disease: An atlas-based diffusion tensor imaging study.

Neuroimage Clin 2019 7;21:101672. Epub 2019 Jan 7.

Department of Neonatology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands. Electronic address:

Background: Brain microstructural maturation progresses rapidly in the third trimester of gestation and first weeks of life, but typical microstructural development may be influenced by the presence of critical congenital heart disease (CHD).

Objective: The aim of this study was to investigate the pattern of white matter (WM) microstructural development in neonates with different types of critical CHD. The secondary aim was to examine whether there is an association between WM microstructural maturity and neonatal ischemic brain injury.

Methods: For this prospective, longitudinal cohort study, 74 term born neonates underwent diffusion tensor imaging (DTI) before (N = 56) and after (N = 71) cardiac surgery performed <30 days of life for transposition of the great arteries (TGA), single ventricle physiology with aortic arch obstruction (SVP-AO), left- (LVOTO) or right ventricle outflow tract obstruction (RVOTO). Microstructural integrity was investigated by fractional anisotropy (FA) and by mean diffusivity (MD) in 16 white matter (WM) structures in three WM regions with correction for postmenstrual age. Ischemic brain injury was defined as moderate-severe white matter injury or stroke.

Results: Before cardiac surgery, the posterior parts of the corona radiata and internal capsule showed significantly higher FA and lower MD compared to the anterior parts. Centrally-located WM structures demonstrated higher FA compared to peripherally-located structures. Neonates with TGA had higher FA in projection-, association- and commissural WM before surgery, when compared to other CHD groups. Neonates with LVOTO showed lower preoperative MD in these regions, and neonates with SVP-AO higher MD. Differences in FA/MD between CHD groups were most clear in centrally located WM structures. Between CHD groups, no differences in postoperative FA/MD or in change from pre- to postoperative FA/MD were seen. Neonatal ischemic brain injury was not associated with pre- or postoperative FA/MD.

Conclusions: Collectively, these findings revealed brain microstructural WM development to follow the same organized pattern in critical CHD as reported in healthy and preterm neonates, from posterior-to-anterior and central-to-peripheral. Neonates with TGA and LVOTO showed the most mature WM microstructure before surgery and SVP-AO the least mature. Degree of WM microstructural immaturity was not associated with ischemic brain injury.
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http://dx.doi.org/10.1016/j.nicl.2019.101672DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6350221PMC
January 2020

Neurodevelopmental Consequences of Preterm Isolated Cerebellar Hemorrhage: A Systematic Review.

Pediatrics 2018 11 19;142(5). Epub 2018 Oct 19.

Department of Neonatology and

Context: The effect of neonatal cerebellar hemorrhage on neurodevelopmental outcome (NDO) in the absence of supratentorial injury is still largely unknown.

Objective: To evaluate the influence of isolated neonatal cerebellar hemorrhage on cognitive, motor, language, and behavioral NDOs and assess the effect of location and size on outcome.

Data Sources: Embase, Medline, and Scopus were searched from inception to September 30, 2017.

Study Selection: Studies in which a diagnosis of isolated cerebellar hemorrhage was reported in preterm infants (<32 weeks' gestation) with a standardized NDO at ≥12 months of age were included.

Data Extraction: Patient characteristics, location, and size of bleeding and NDO (defined as severe [yes or no] on the basis of given cutoff points) in 4 domains were extracted.

Results: Of the 1519 studies identified, 8 were included in final analyses. Of infants with isolated cerebellar hemorrhage, 128 were described (cumulative incidence: 2.3%). The incidence of severe delay in cognition, motor, language, and behavioral development was 38%, 39%, 41%, and 38%, respectively. The overall incidence of severe neurodevelopmental delay in ≥1 domain ranged from 43% to 75% and was most seen in infants with vermis involvement (87%-93%) and with large bleeds (46%-82%).

Limitations: Different neurodevelopmental scales lead to data heterogeneity, and reporting of data on a group level limited possibilities for an outcome description on an individual level.

Conclusions: Of infants with isolated cerebellar hemorrhage, 43% to 75% were severely delayed in cognition, motor, language, and/or behavioral development, with the highest incidence with vermis involvement and with large bleeds.
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http://dx.doi.org/10.1542/peds.2018-0609DOI Listing
November 2018

Electroencephalography and brain magnetic resonance imaging in asphyxia comparing cooled and non-cooled infants.

Eur J Paediatr Neurol 2019 Jan 12;23(1):181-190. Epub 2018 Sep 12.

Department of Pediatrics, Division of Neonatology, Erasmus MC-Sophia Children's Hospital, Wytemaweg 80, 3015 CN, Rotterdam, the Netherlands; Department of Pediatrics, Division of Neonatology, Wilhelmina Children's Hospital, University Medical Center, Heidelberglaan 100, 3584 CX, Utrecht, the Netherlands. Electronic address:

Objective: The aim was to establish any differences in the predictive value of EEG and MRI for outcome in infants treated and not-treated with therapeutic hypothermia (HT) for perinatal asphyxia. We hypothesize that they are equally predictive and that combining both has the highest predictive value.

Study Design: We retrospectively compared data of infants with hypoxic-ischemic encephalopathy (HIE) who received HT (n = 45) between September 2009 and December 2013 with those of infants with HIE born between January 2004 and August 2009, before HT was available (NT, n = 37). All received conventional and/or amplitude-integrated EEG during the first days and early MRI (day 4-5). Associations of EEG, MRI and severe neurodevelopmental outcome (death or Bayley's -2SD below mean), were tested with a multivariable logistic regression analysis, corrected for HT.

Results: Forty-eight hours' EEG background pattern had a PPV of 92% and a NPV of 81% in HT, versus 100% and 58% in NT. MRI had a PPV of 71% and a NPV of 93% in HT, versus 82% and 75% in NT. The adjusted OR for adverse outcome was 0.013 (95% CI 0.002-0.154, p < 0.001) for EEG background normalization within 48 h and 32.19 (95% CI 4.84-214.25, p < 0.001) for abnormal MRI.

Conclusion: The predictive value of EEG and MRI is equal in cooled and non-cooled infants with HIE. Our data show a higher predictive value (death and severe outcome) for EEG compared to MRI. In HIE, persistent abnormal EEG background pattern until 48 h, combined with abnormal early MRI is strongly predictive for poor neurodevelopment.
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http://dx.doi.org/10.1016/j.ejpn.2018.09.001DOI Listing
January 2019

Correction: Language outcome related to brain structures in school-aged preterm children: A systematic review.

PLoS One 2018 27;13(8):e0203298. Epub 2018 Aug 27.

[This corrects the article DOI: 10.1371/journal.pone.0196607.].
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0203298PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6110488PMC
August 2018

Language outcome related to brain structures in school-aged preterm children: A systematic review.

PLoS One 2018 4;13(6):e0196607. Epub 2018 Jun 4.

Division of Neonatology, Department of Pediatrics at Erasmus Medical University Centre-Sophia Children's Hospital, Rotterdam, Netherlands.

Preterm children often have language problems. This atypical language development is probably due to atypical brain development. We conducted a systematic review to provide an overview of the extensive and diverse scientific literature on the relations between language outcome and underlying brain structures in school-aged preterm-born children. Embase, Medline Ovid, Web of Science, Cochrane central and Google scholar were searched for relevant studies. Inclusion criteria were: cases are school-aged preterm children; structural MRI (T1- and T2-weighted sequences) or DTI used in combination with a neurocognitive language test; publication in an English-language peer-reviewed journal. Correlational measures between language scores and brain volume or fractional anisotropy of a brain structure were extracted. 23 studies were included. The relations between oral language, verbal fluency and/or written language and MRI/DTI measurements of white matter, gray matter, cerebellum, corpus callosum and/or the fasciculi are presented. Oral language skills and verbal fluency appear to be related to the corpus callosum. Oral language skills are also related to the uncinate fasciculus. There seems to be no clear relation between cerebellar development and verbal fluency skills. Not one single brain area is responsible for atypical language development, but several brain areas and their connections are essential. For future research it is recommended to relate brain areas to oral language skills on a microstructural level in preterm children. We also recommend to use language tests in which it is possible to distinguish between several language domains, such as perceptive and expressive language.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0196607PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5986152PMC
November 2018