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Very preterm birth (VPT; <32 weeks' gestation) leads to a situation where crucial steps of brain development occur in an abnormal ex utero environment, translating to vulnerable cortical and subcortical development. Associated with this atypical brain development, children and adolescents born VPT are at a high risk of socio-emotional difficulties. In the current study, we unravel developmental changes in cortical gray matter (GM) concentration in VPT and term-born controls aged 6-14 years, together with their associations with socio-emotional abilities. T1-weighted images were used to estimate signal intensities of brain tissue types in a single voxel (GM, white matter, and cortico-spinal fluid) and extract GM concentration disentangled from the presence of partial volume effects (PVEs). General linear model analysis was used to compare groups. Socio-emotional abilities were assessed and associations with GM concentration were explored using univariate and multivariate analyses. The effects of prematurity were far-reaching, with intricated patterns of increases and decreases of GM concentration mainly in frontal, temporal, parietal, and cingular regions. Better socio-emotional abilities were associated with increased GM concentration in regions known to be involved in such process for both groups. Our findings suggest that the trajectory of brain development following VPT birth may be fundamentally distinctive and impact socio-emotional abilities., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Very preterm (VPT) children and adolescents show executive, behavioural and socio-emotional difficulties that persist into adulthood. Despite the promising role of mindfulness-based intervention (MBI) in improving theses competences in children and adolescents, the effectiveness of an MBI has not been assessed in a VPT population so far., Aims: To describe the protocol and to evaluate the feasibility and acceptability of a clinical trial on an 8-week MBI program to enhance executive and socio-emotional competences in a cohort of VPT young adolescents., Study Design: A randomised controlled trial (RCT) and a pre-post intervention designs., Participants: 164 VPT young adolescents from 10 to 14 years old, born before 32 gestational weeks, without major intellectual, sensory or physical impairments, and attending mainstream school, were invited to participate in an 8-week MBI program., Outcome Measures: Completion rate of the study was recorded. Acceptability, satisfaction and attendance measures of the MBI were collected using self-reported questionnaires and registration of attendance., Results: Of the 63 participants who were enrolled in the study (38.2% of families invited to participate), 52 (82.5%) completed all assessments. Acceptability was high as shown by the high attendance rate in the sessions and the feedback evaluation questionnaire., Conclusions: Our findings suggest that an MBI is feasible to implement and show a high acceptability among participants. The use of an RCT design in our study constitutes the gold standard for testing the efficacy of such intervention in VPT young adolescents. If effective, the MBI program could potentially be a valuable tool for improving executive and socio-emotional competences in the vulnerable VPT population., Trial Registration: ClinicalTrials, NCT04638101. Registered 19 November 2020 - retrospectively registered, https://clinicaltrials.gov/show/NCT04638101., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Arthrogryposis describes the presence of multiple joint-contractures. Clinical severity of this phenotype is variable, and more than 400 causative genes have been proposed. Among these, ERGIC1 is a recently reported candidate encoding a putative transmembrane protein of the ER-Golgi interface. Two homozygous missense variants have been reported in patients with relatively mild non-syndromic arthrogryposis. In a consanguineous family with two affected siblings presenting congenital arthrogryposis and some facial dysmorphism we performed prenatal array-CGH, postnatal targeted exome and genome sequencing. Genome sequencing identified a homozygous 22.6 Kb deletion encompassing the promoter and first exon of ERGIC1. mRNA quantification showed the complete absence of ERGIC1 expression in the two affected siblings and a decrease in heterozygous parents. Our observations validate the pathogenic role of ERGIC1 in congenital arthrogryposis and demonstrate that complete loss of function causes a relatively mild phenotype. These findings will contribute to improve genetic counseling of ERGIC1 mutations., (© 2021 The Authors. Clinical Genetics published by John Wiley & Sons Ltd.)

Maternal voice is a highly relevant stimulus for newborns. Adult voice processing occurs in specific brain regions. Voice-specific brain areas in newborns and the relevance of an early vocal exposure on these networks have not been defined. This study investigates voice perception in newborns and the impact of prematurity on the cerebral processes. Functional magnetic resonance imaging (fMRI) and high-density electroencephalography (EEG) were used to explore the brain responses to maternal and stranger female voices in full-term newborns and preterm infants at term-equivalent age (TEA). fMRI results and the EEG oddball paradigm showed enhanced processing for voices in preterms at TEA than in full-term infants. Preterm infants showed additional cortical regions involved in voice processing in fMRI and a late mismatch response for maternal voice, considered as a first trace of a recognition process based on memory representation. Full-term newborns showed increased cerebral activity to the stranger voice. Results from fMRI, oddball, and standard auditory EEG paradigms highlighted important change detection responses to novelty after birth. These findings suggest that the main components of the adult voice-processing networks emerge early in development. Moreover, an early postnatal exposure to voices in premature infants might enhance their capacity to process voices., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Importance: Premature infants are at risk of developing encephalopathy of prematurity, which is associated with long-term neurodevelopmental delay. Erythropoietin was shown to be neuroprotective in experimental and retrospective clinical studies., Objective: To determine if there is an association between early high-dose recombinant human erythropoietin treatment in preterm infants and biomarkers of encephalopathy of prematurity on magnetic resonance imaging (MRI) at term-equivalent age., Design, Setting, and Participants: A total of 495 infants were included in a randomized, double-blind, placebo-controlled study conducted in Switzerland between 2005 and 2012. In a nonrandomized subset of 165 infants (n=77 erythropoietin; n=88 placebo), brain abnormalities were evaluated on MRI acquired at term-equivalent age., Interventions: Participants were randomly assigned to receive recombinant human erythropoietin (3000 IU/kg; n=256) or placebo (n=239) intravenously before 3 hours, at 12 to 18 hours, and at 36 to 42 hours after birth., Main Outcomes and Measures: The primary outcome of the trial, neurodevelopment at 24 months, has not yet been assessed. The secondary outcome, white matter disease of the preterm infant, was semiquantitatively assessed from MRI at term-equivalent age based on an established scoring method. The resulting white matter injury and gray matter injury scores were categorized as normal or abnormal according to thresholds established in the literature by correlation with neurodevelopmental outcome., Results: At term-equivalent age, compared with untreated controls, fewer infants treated with recombinant human erythropoietin had abnormal scores for white matter injury (22% [17/77] vs 36% [32/88]; adjusted risk ratio [RR], 0.58; 95% CI, 0.35-0.96), white matter signal intensity (3% [2/77] vs 11% [10/88]; adjusted RR, 0.20; 95% CI, 0.05-0.90), periventricular white matter loss (18% [14/77] vs 33% [29/88]; adjusted RR, 0.53; 95% CI, 0.30-0.92), and gray matter injury (7% [5/77] vs 19% [17/88]; adjusted RR, 0.34; 95% CI, 0.13-0.89)., Conclusions and Relevance: In an analysis of secondary outcomes of a randomized clinical trial of preterm infants, high-dose erythropoietin treatment within 42 hours after birth was associated with a reduced risk of brain injury on MRI. These findings require assessment in a randomized trial designed primarily to assess this outcome as well as investigation of the association with neurodevelopmental outcomes., Trial Registration: clinicaltrials.gov Identifier: NCT00413946.

Background: Amplitude-integrated electroencephalogram (aEEG) is a reliable monitoring tool for electrocortical activity with good predictive value in preterm infants. Magnetic resonance imaging (MRI) is a good neuroimaging tool to detect brain lesions and to evaluate brain maturation. We hypothesized that early aEEG measures, recorded over the first 3 d of life in very preterm infants, correlate with brain maturation and injury score assessed by conventional MRI at term-equivalent age., Methods: Thirty-nine infants born at a mean (range) gestational age (GA) of 29.5 (27.0-31.9) wk and birth weight 1,230 (680-2,020) g had continuous aEEG during the first postnatal 72-84 h. aEEG maturity scores and average maximum and minimum amplitudes were evaluated. Conventional brain MRI was performed at 41.2 (37.1-44.1) wk postmenstrual age (PMA) on a 3T GE system and scored qualitatively for injury and maturation., Results: The average aEEG total maturity score and its cycling subscore were positively and significantly associated with the total MRI maturation score after adjustment for GA, morphine sedation, and PMA at MRI examination. No association was found between the aEEG measures and the MRI injury scores., Conclusion: Early aEEG maturity seems to relate to structural MRI brain maturation at term-equivalent age in preterm infants.

Congenital hypothyroidism (CH) can lead to intellectual deficits despite early high-dose treatment. Our study aimed to determine whether motor impairments can occur despite early high-dose treatment. Sixty-three children with CH and early (median age of onset of treatment 9 d), high-dose treatment (median starting dose of levothyroxine 14.7 μg/kg/d) were tested with the Zurich Neuromotor Assessment (ZNA) at a median age of 13.8 y (range 7.0-14.2 y). Median z-scores in the children with CH were -0.95 in the pure and -0.56 in the adaptive fine motor component, significantly lower than in the ZNA test norms (p < 0.001 and p = 0.01, respectively). The 26 children with athyreosis were more affected than the 33 children with dysgenesis, particularly in the pure motor (-1.55 versus -0.76, p = 0.03), adaptive fine motor (-1.31 versus 0.13, p < 0.01), and static balance task (-0.47 versus 0.67, p = 0.01). Boys performed worse than girls. Older age at onset of treatment was related to poorer adaptive fine motor performance. Movement quality (assessed by associated movements) was not affected. We conclude that severe CH can cause neuromotor deficits persisting into adolescence. These deficits cannot completely be reversed by postnatal treatment, but earlier age at treatment may reduce the degree of impairment.

During the last trimester of human pregnancy, the cerebral cortex of foetuses becomes greatly and quickly gyrified, and post-mortem studies have demonstrated that hemispheres are already asymmetric at the level of Heschl gyrus, planum temporale and superior temporal sulcus (STS). Recently, magnetic resonance imaging (MRI) and dedicated post-processing tools enabled the quantitative study of brain development non-invasively in the preterm newborn. However, previous investigations were conducted either over the whole brain or in specific sulci. These approaches may consequently fail to highlight most cerebral sites, where anatomical landmarks are hard to delineate among individuals. In this cross-sectional study, we aimed to blindly and automatically map early asymmetries over the immature cortex. Voxel-based analyses of cortical and white matter masks were performed over a group of 25 newborns from 26 to 36 weeks of gestational age. Inter-individual variations associated with increasing age were first detected in large cerebral regions, with a prevalence of the right hemisphere in comparison with the left. Asymmetries were further highlighted in three specific cortical regions. Confirming previous studies, we observed deeper STS on the right side and larger posterior region of the sylvian fissure on the left side, close to planum temporale. For the first time, we also detected larger anterior region of the sylvian fissure on the left side, close to Broca's region. This study demonstrated that perisylvian regions are the only regions to be asymmetric from early on, suggesting their anatomical specificity for the emergence of functional lateralization in language processing prior to language exposure., (Copyright 2010 Elsevier Inc. All rights reserved.)