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Objectives: We analyzed the impact of postoperative necrotizing enterocolitis (NEC) after cardiac surgery in neonatal age on neurodevelopmental (ND) outcome at 1 year of age. Methods: Using data from the Swiss Neurodevelopmental Outcome Registry for Children with Congenital Heart Disease (ORCHID), we analyzed perioperative variables including postoperative NEC (Bell's stage ≥2) and 1-year ND outcome (Bayley III). Results: The included patients (n = 101) had congenital heart disease (CHD), categorized as follows: 77 underwent biventricular repair for CHD with two functional chambers, 22 underwent staged palliation until the Fontan procedure for CHD with single ventricle physiology (n = 22), or 4 underwent single ventricle palliation or biventricular repair for borderline CHD (n = 4). Neonatal cardiopulmonary bypass (CBP) surgery was performed at a median age (IQR) of 8 (6) days. NEC occurred in 16 patients. Intensive care unit (ICU) length of stay (LOS) and the total duration of the hospitalization were longer in children with NEC than those in others (14 with vs. 8 days without NEC, p < 0.05; 49 with vs. 32 days without NEC, p < 0.05). The Bayley III scores of the analyzed patients determined at an age of 11.5 ± 1.5 months showed cognitive (CCS) (102.2 ± 15.0) and language scores (LCS) (93.8 ± 13.1) in the normal range and motor composite scores (MCS) (88.7 ± 15.9) in the low-normal range. After adjusting for socioeconomic status and CHD type, patients with NEC had lower CCS scores [ß = -11.2 (SE 5.6), p = 0.049]. Using a cumulative risk score including NEC, we found a higher risk score to be associated with both lower CCS [ß = -2.8 (SE 1.3), p = 0.030] and lower MCS [ßâ =â -3.20 (SE 1.3), p = 0.016]. Conclusions: Postoperative NEC is associated with longer ICU and hospital LOS and contributes together with other complications to impaired ND outcome at 1 year of age. In the future, national and international patient registries may provide the opportunity to analyze large cohorts and better identify the impact of modifiable perioperative risk factors on ND outcome. Clinical Trial Registration: ClinicalTrials.gov identifier: NCT05996211.
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AIM: Adolescents born very preterm (VPT; <32 weeks of gestation) face an elevated risk of executive, behavioral, and socioemotional difficulties. Evidence suggests beneficial effects of mindfulness-based intervention (MBI) on these abilities. This study seeks to investigate the association between the effects of MBI on executive, behavioral, and socioemotional functioning and reliable changes in large-scale brain networks dynamics during rest in VPT young adolescents who completed an 8-week MBI program. METHODS: Neurobehavioral assessments and resting-state functional magnetic resonance imaging were performed before and after MBI in 32 VPT young adolescents. Neurobehavioral abilities in VPT participants were compared with full-term controls. In the VPT group, dynamic functional connectivity was extracted by using the innovation-driven coactivation patterns framework. The reliable change index was used to quantify change after MBI. A multivariate data-driven approach was used to explore associations between MBI-related changes on neurobehavioral measures and temporal brain dynamics. RESULTS: Compared with term-born controls, VPT adolescents showed reduced executive and socioemotional functioning before MBI. After MBI, a significant improvement was observed for all measures that were previously reduced in the VPT group. The increase in executive functioning, only, was associated with reliable changes in the duration of activation of large-scale brain networks, including frontolimbic, amygdala-hippocampus, dorsolateral prefrontal, and visual networks. CONCLUSION: The improvement in executive functioning after an MBI was associated with reliable changes in large-scale brain network dynamics during rest. These changes encompassed frontolimbic, amygdala-hippocampus, dorsolateral prefrontal, and visual networks that are related to different executive processes including self-regulation, attentional control, and attentional awareness of relevant sensory stimuli.
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Função Executiva , Imageamento por Ressonância Magnética , Atenção Plena , Rede Nervosa , Humanos , Atenção Plena/métodos , Adolescente , Masculino , Feminino , Função Executiva/fisiologia , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiopatologia , Rede Nervosa/fisiologia , Lactente Extremamente Prematuro/fisiologia , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , ConectomaRESUMO
BACKGROUND: Socio-emotional difficulties often result from very preterm (VPT) birth. The amygdala's developmental trajectory, including its nuclei, has been recognized as a significant factor in observed difficulties. This study aims to assess the relationship between amygdala volume and socio-emotional competencies in VPT children and adolescents. METHODS: Socio-emotional competencies were assessed, and amygdala volumes, including subnuclei, were extracted automatically from structural scans in a cross-sectional cohort of VPT (n = 75) and full-term (FT, n = 41) aged 6-14 years. Group differences in amygdala volumes were assessed using ANCOVA, and associations with socio-emotional competencies were studied using partial least squares correlation (PLSC). In a VPT subgroup, additional longitudinal data with amygdala volumes at term-equivalent age (TEA) were manually extracted, growth rates calculated, and associations with school-age socio-emotional competencies investigated using PLSC. RESULTS: Using cross-sectional data at school-age, amygdala volumes displayed comparable developmental patterns between the VPT and the FT groups. Greater volumes were associated with more emotional regulation difficulties in VPT and lower affect recognition competencies in FT. In the longitudinal VPT subgroup, no significant associations were found between amygdala volume trajectory and socio-emotional competencies. CONCLUSION: Although our findings suggest typical amygdala development after VPT birth, further research is necessary to elucidate the developmental trajectory of amygdala and the role of resilience factors. IMPACT: In our cohort, amygdala volumes, including subnuclei, displayed comparable developmental trajectories between the very preterm and the full-term groups. Higher amygdala volumes at school-age were associated with higher emotional regulation difficulties in the very-preterm born group, and with lower affect recognition abilities in full-term born children and adolescents. In a subgroup of very-preterm children and adolescents followed from birth to school-age, no significant associations were found between amygdala volumes at term-equivalent age and socio-emotional competencies at school-age.
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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.
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Nascimento Prematuro , Substância Branca , Feminino , Humanos , Criança , Recém-Nascido , Adolescente , Encéfalo , Recém-Nascido Prematuro/psicologia , Emoções , Imageamento por Ressonância Magnética/métodosRESUMO
Previous studies suggest that structural alteration of the corpus callosum, i.e., the largest white matter commissural pathway, occurs after a preterm birth in the neonatal period and lasts across development. The present study aims to unravel corpus callosum structural characteristics across childhood and adolescence in very preterm (VPT) individuals, and their associations with general intellectual, executive and socio-emotional functioning. Neuropsychological assessments, T1-weighted and multi-shell diffusion MRI were collected in 79 VPT and 46 full term controls aged 6-14 years. Volumetric, diffusion tensor and neurite orientation dispersion and density imaging (NODDI) measures were extracted on 7 callosal portions using TractSeg. A multivariate data-driven approach (partial least squares correlation) and a cohort-based age normative modelling approach were used to explore associations between callosal characteristics and neuropsychological outcomes. The VPT and a full-term control groups showed similar trends of white-matter maturation over time, i.e., increase FA and reduced ODI, in all callosal segments, that was associated with increase in general intellectual functioning. However, using a cohort-based age-related normative modelling, findings show atypical pattern of callosal development in the VPT group, with reduced callosal maturation over time that was associated with poorer general intellectual and working memory functioning, as well as with lower gestational age.
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Cognição , Corpo Caloso , Lactente Extremamente Prematuro , Adolescente , Criança , Humanos , Recém-Nascido , Cognição/fisiologia , Corpo Caloso/anatomia & histologia , Corpo Caloso/diagnóstico por imagem , Corpo Caloso/crescimento & desenvolvimento , Idade Gestacional , Lactente Extremamente Prematuro/crescimento & desenvolvimento , Neuropsicologia , Imageamento por Ressonância MagnéticaRESUMO
Very preterm (VPT) young adolescents are at high risk of executive, behavioural and socio-emotional difficulties. Previous research has shown significant evidence of the benefits of mindfulness-based intervention (MBI) on these abilities. This study aims to assess the association between the effects of MBI on neurobehavioral functioning and changes in white-matter microstructure in VPT young adolescents who completed an 8-week MBI program. Neurobehavioural assessments (i.e., neuropsychological testing, parents- and self-reported questionnaires) and multi-shell diffusion MRI were performed before and after MBI in 32 VPT young adolescents. Combined diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) measures were extracted on well-defined white matter tracts (TractSeg). A multivariate data-driven approach (partial least squares correlation) was used to explore associations between MBI-related changes on neurobehavioural measures and microstructural changes. The results showed an enhancement of global executive functioning using parent-reported questionnaire after MBI that was associated with a general pattern of increase in fractional anisotropy (FA) and decrease in axonal dispersion (ODI) in white-matter tracts involved in executive processes. Young VPT adolescents with lower gestational age at birth showed the greatest gain in white-matter microstructural changes after MBI.
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Atenção Plena , Substância Branca , Recém-Nascido , Feminino , Humanos , Adolescente , Imagem de Tensor de Difusão/métodos , Encéfalo , Substância Branca/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética/métodos , NeuritosRESUMO
OBJECTIVE: Prematurity is associated with a high risk of long-term behavioral problems. This study aimed to assess the prognostic utility of volumetric brain data at term-equivalent-age (TEA), clinical perinatal factors, and parental social economic risk in the prediction of the behavioral outcome at 5 years in a cohort of very preterm infants (VPT, <32 gestational weeks). METHODS: T2-weighted magnetic resonance brain images of 80 VPT children were acquired at TEA and automatically segmented into cortical gray matter, deep subcortical gray matter, white matter (WM), cerebellum (CB), and cerebrospinal fluid. The gray matter structure of the amygdala was manually segmented. Children were examined at 5 years of age with a behavioral assessment, using the strengths and difficulties questionnaire (SDQ). The utility of brain volumes at TEA, perinatal factors, and social economic risk for the prediction of behavioral outcome was investigated using support vector machine classifiers and permutation feature importance. RESULTS: The predictive modeling of the volumetric data showed that WM, amygdala, and CB volumes were the best predictors of the SDQ emotional symptoms score. Among the perinatal factors, sex, sepsis, and bronchopulmonary dysplasia were the best predictors of the hyperactivity/inattention score. When combining the social economic risk with volumetric and perinatal factors, we were able to accurately predict the emotional symptoms score. Finally, social economic risk was positively correlated with the scores of conduct problems and peer problems. CONCLUSIONS: This study provides information on the relation between brain structure at TEA and clinical perinatal factors with behavioral outcome at age 5 years in VPT children. Nevertheless, the overall predictive power of our models is relatively modest, and further research is needed to identify factors associated with subsequent behavioral problems in this population.
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Encéfalo , Lactente Extremamente Prematuro , Lactente , Feminino , Humanos , Recém-Nascido , Criança , Pré-Escolar , Prognóstico , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Imageamento por Ressonância Magnética/métodos , Substância Cinzenta/diagnóstico por imagem , Idade GestacionalRESUMO
BACKGROUND: Children born very preterm (VPT; <32 weeks' gestation) are at high risk of neurodevelopmental and behavioural difficulties associated with atypical brain maturation, including socio-emotional difficulties. The analysis of large-scale brain network dynamics during rest allows us to investigate brain functional connectivity and its association with behavioural outcomes. METHODS: Dynamic functional connectivity was extracted by using the innovation-driven co-activation patterns framework in VPT and full-term children aged 6-9 to explore changes in spatial organisation, laterality and temporal dynamics of spontaneous large-scale brain activity (VPT, n = 28; full-term, n = 12). Multivariate analysis was used to explore potential biomarkers for socio-emotional difficulties in VPT children. RESULTS: The spatial organisation of the 13 retrieved functional networks was comparable across groups. Dynamic features and lateralisation of network brain activity were also comparable for all brain networks. Multivariate analysis unveiled group differences in associations between dynamical functional connectivity parameters with socio-emotional abilities. CONCLUSION: In this exploratory study, the group differences observed might reflect reduced degrees of maturation of functional architecture in the VPT group in regard to socio-emotional abilities. Dynamic features of functional connectivity could represent relevant neuroimaging markers and inform on potential mechanisms through which preterm birth leads to neurodevelopmental and behavioural disorders. IMPACT: Spatial organisation of the retrieved resting-state networks was comparable between school-aged very preterm and full-term children. Dynamic features and lateralisation of network brain activity were also comparable across groups. Multivariate pattern analysis revealed different patterns of association between dynamical functional connectivity parameters and socio-emotional abilities in the very preterm and full-term groups. Findings suggest a reduced degree of maturation of the functional architecture in the very preterm group in association with socio-emotional abilities.
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Lactente Extremamente Prematuro , Nascimento Prematuro , Feminino , Humanos , Recém-Nascido , Criança , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Emoções , Idade Gestacional , Imageamento por Ressonância MagnéticaRESUMO
Developmental care is defined by a personalized approach to the premature child. Observation of sensory-motor behavior is a key part of this approach and requires specific training and the use of observation tools. This study analyzes the use of an illustrated guide during the observation and evaluation of the sensory-motor behavior of the premature baby; this didactic contribution constitutes a real added value for the professionals, allowing the elaboration of a care project.
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Doenças do Prematuro , Nascimento Prematuro , Criança , Criança Hospitalizada , Família , Feminino , Humanos , Lactente , Recém-NascidoRESUMO
Very preterm (VPT) children and adolescents show executive, behavioural and socio-emotional difficulties that persists into adulthood. This study aims to assess the effectiveness of a mindfulness-based intervention (MBI) in improving these competencies in VPT young adolescents using a randomised controlled trial design. 56 young adolescents aged 10-14 years, born before 32 gestational weeks, were randomly assigned to an "intervention" or a "waiting" group and completed an 8-week MBI in a cross-over design. Executive, behavioural and socio-emotional competencies were assessed at three different time points via parent and self-reported questionnaires, neuropsychological testing and computerised tasks. The data were analysed using an intention-to-treat approach with linear regression modelling. Our findings show a beneficial effect of MBI on executive, behavioural and socio-emotional competencies in VPT young adolescents measured by parent questionnaires. Increased executive competencies were also observed on computerised task with enhanced speed of processing after MBI. Two subgroups of participants were created based on measures of prematurity, which revealed increased long-term benefits in the moderate-risk that were not observed in the high-risk subgroups of VPT young adolescents. MBI seems a valuable tool for reducing detrimental consequences of prematurity in young adolescents, especially regarding executive, behavioural and socio-emotional difficulties.Clinical Trial Registration ClinicalTrials, NCT04638101. Registered 20 November 2020-Retrospectively registered, https://clinicaltrials.gov/show/NCT04638101 .
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Emoções , Função Executiva , Lactente Extremamente Prematuro , Atenção Plena , Nascimento Prematuro/epidemiologia , Comportamento Social , Adolescente , Comportamento do Adolescente/psicologia , Desenvolvimento do Adolescente , Criança , Comportamento Infantil/psicologia , Desenvolvimento Infantil , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Atenção Plena/métodos , Nascimento Prematuro/psicologiaRESUMO
The main aim of the present study was to investigate the effects of the COVID-19 pandemic on the mothers' postnatal depression, stress, and attachment during their stay in the Neonatal Intensive Care Unit (NICU). Twenty mothers of very premature infants born before 32weeks of gestational age were recruited at the Geneva University Hospital between January 2018 and February 2020 before the COVID-19 pandemic started. Mothers were screened for postnatal depression after their preterm infant's birth (Edinburgh Postnatal Depression Scale, EPDS), then for stress (Parental Stressor Scale: Neonatal Intensive Care Unit, PSS:NICU), and attachment (Maternal Postnatal Attachment Scale, MPAS) at infant's term-equivalent age. Data were compared with 14 mothers recruited between November 2020 and June 2021 during the COVID-19 pandemic. No significant differences were found in the scores for depression, stress, and attachment between the two groups. However, a non-statistically significant trend showed a general increase of depression symptoms in mothers during the COVID-19 pandemic, which significantly correlated to the attachment and stress scores. Moreover, the PSS:NICU Sights and Sounds score was significantly positively correlated with EPDS scores and negatively with the MPAS score only in the During-COVID group. To conclude, we discussed a possible dampened effect of the several protective family-based actions that have been adopted in the Geneva University Hospital during the health crisis, and we discussed the most appropriate interventions to support parents in this traumatic period during the COVID-19 pandemic.
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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.
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Atenção Plena , Adolescente , Criança , Emoções , Estudos de Viabilidade , Humanos , Lactente Extremamente Prematuro , Recém-Nascido , Atenção Plena/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Inquéritos e QuestionáriosRESUMO
Preterm birth is one of the main causes for neurodevelopmental problems, and has been associated with a wide range of impairments in cognitive functions including executive functions and memory. One of the factors contributing to these adverse outcomes is the intrinsic vulnerability of the premature brain. Neuroimaging studies have highlighted structural and functional alterations in several brain regions in preterm individuals across lifetime. The orbitofrontal cortex (OFC) is crucial for a multitude of complex and adaptive behaviours, and its structure is particularly affected by premature birth. Nevertheless, studies on the functional impact of prematurity on the OFC are still missing. Orbitofrontal Reality filtering (ORFi) refers to the ability to distinguish if a thought is relevant to present reality or not. It can be tested using a continuous recognition task and is mediated by the OFC in adults and typically developing young adolescents. Therefore, the ORFi task was used to investigate whether OFC functioning is affected by prematurity. We compared the neural correlates of ORFi in 35 young adolescents born preterm (below 32 weeks of gestation) and aged 10 to 14 years with 25 full term-born controls. Our findings indicate that OFC activation was required only in the full-term group, whereas preterm young adolescents did not involve OFC in processing the ORFi task, despite being able to correctly perform it.
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Nascimento Prematuro , Adolescente , Adulto , Encéfalo , Função Executiva , Feminino , Humanos , Recém-Nascido , Córtex Pré-Frontal/diagnóstico por imagem , Gravidez , Reconhecimento PsicológicoRESUMO
Mindfulness based interventions (MBI) are widely available to adults. Programs are also offered to children and adolescents. Interventions in school and clinical settings are increasingly being published in scientific literature. In the school context, the effects are promising on psychological health, such as stress, anxiety, depression or externalized behaviours, and on executive functions, attention, and socio-emotional skills. In the clinical context, MBI has a particular effect on stress/anxiety and depression as well as on the key symptoms of Attention Deficit Hyperactivity Disorder. These results are very encouraging, but all meta-analyses and literature reviews nevertheless emphasize the need for studies with robust methodology before proposing MBI on a large scale for this population.
Les interventions basées sur la pleine conscience (MBI) sont de plus en plus proposées aux enfants et aux adolescents et font l'objet de nombreuses publications scientifiques. Dans le contexte scolaire, les effets sont prometteurs sur la santé psychologique, comme le stress, l'anxiété, la dépression ou les comportements externalisés et sur les fonctions exécutives, l'attention, et les compétences socioémotionnelles. Dans le contexte clinique, les MBI ont un effet en particulier sur le stress/l'anxiété et la dépression ainsi que sur les symptômes clés du trouble du déficit d'attention avec hyperactivité. Ces résultats sont très encourageants mais toutes les méta-analyses et les revues de la littérature soulignent néanmoins la nécessité de faire des études à la méthodologie robuste avant de proposer des MBI à large échelle.
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Ansiedade/terapia , Transtorno do Deficit de Atenção com Hiperatividade/terapia , Depressão/terapia , Saúde Mental , Atenção Plena , Adolescente , Criança , Emoções , HumanosRESUMO
INTRODUCTION: Children born very preterm (VPT) are at increased risk of emotional and behavioral problems later in life. We aimed to determine the prevalence and spectrum of behavioral abnormalities at five years of age in VPT children. METHODS: Multi-center cohort study on 339 early-school aged children born at a gestational age below 32 weeks, between 2008 and 2011 and followed through the SwissNeoNet. Behavior was assessed with the Strength and Difficulties Questionnaire and compared to published German norms. Analysis of perinatal, neonatal, socio-economic and neurodevelopmental risk factors was performed using multivariable logistic regression. RESULTS: 30.7% of 1105 VPT surviving children were assessed at mean age 67.3 months (SD 5.9). Compared to the reference population, VPT children had significantly higher scores for emotional symptoms (odds ratio 1.53, 95% confidence interval 1.11.-2.12), while the total difficulties score was similar (1.16, 0.85-1.58). Lower socioeconomic status was the only independent predictor of at-risk behavior (borderline and abnormal behavior). CONCLUSION: The spectrum of behavioral abnormalities in a current Swiss cohort of VPT children differs from the previously published data as hyperactivity was not a prominent symptom. Instead, emotional problems were reported to occur more frequently, with an increased prevalence for those coming from a lower socioeconomic background.
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Deficiências do Desenvolvimento/epidemiologia , Recém-Nascido Prematuro/crescimento & desenvolvimento , Comportamento Problema , Criança , Desenvolvimento Infantil , Deficiências do Desenvolvimento/psicologia , Emoções , Feminino , Humanos , Recém-Nascido , Recém-Nascido Prematuro/psicologia , Masculino , Fatores SocioeconômicosRESUMO
OBJECTIVE: To validate and test a German version of the revised Parent Report of Children's Abilities questionnaire (PARCA-R). METHODS: Multicentre cross-sectional study. Parents of infants born <32 gestational weeks, completed the PARCA-R within three weeks before the follow-up assessment of their child at age two years. Infants were assessed using the Mental Development Index (MDI) of the Bayley Scales of Infant Development 2nd edition (BSID-II). Pearson correlation between the Parent Report Composite (PRC) of the PARCA-R and MDI was tested. The optimal PRC cut-off for predicting moderate-to-severe mental delay, defined as MDI<70, was identified through the receiver operating characteristic (ROC) curve. RESULTS: PARCA-R and BSID-II data were collected from 154 consecutive infants [51% girls, mean (SD) gestational age 29.0 (2.0) weeks, birth weight 1174 (345) grams] at 23.2 (1.6) months of corrected age. The PRC score [70.5 (31.1)] correlated with the MDI [92.2 (17.3); R = 0.54; p < 0.0001]. The optimal PRC cut-off for identifying mental delay was 44 with 0.81 (0.54-0.96) sensitivity (95%-CI), 0.81 (0.74-0.87) specificity, area under the ROC curve of 0.840 (0.729-0.952). CONCLUSION: The German version of the PARCA-R had good validity with the BSID-II and PCR scores < 44 proved optimal discriminatory power for the identification of mental delay at two years of corrected age.
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Desenvolvimento Infantil , Recém-Nascido Prematuro , Transtornos do Neurodesenvolvimento/diagnóstico , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro/fisiologia , Masculino , Transtornos do Neurodesenvolvimento/epidemiologia , Inquéritos e Questionários , Suíça/epidemiologiaRESUMO
BACKGROUND AND OBJECTIVES: Escitalopram (SCIT) is frequently prescribed to breastfeeding women. Available information on SCIT excretion into breast milk is based on heterogeneous and incomplete data. A population pharmacokinetic model that aimed to better characterize maternal and infant exposure to SCIT and its metabolite was developed. METHODS: The study population was composed of women treated by SCIT or racemic citalopram and enrolled in the multicenter prospective cohort study SSRI-Breast Milk study (ClinicalTrial.gov NCT01796132). A joint structural model was first built for SCIT and S-desmethylcitalopram (SDCIT) in plasma using NONMEM and the milk-to-plasma ratio (MPR) was estimated by adding the drug breast milk concentrations. The effect of different influential covariates was tested and the average drug exposure with variability through breastfeeding was predicted under various conditions by simulation. RESULTS: The study enrolled 33 patients treated with SCIT or racemic citalopram who provided 80 blood and 104 milk samples. Mean MPR for both parent drug and metabolite was 1.9. Increased milk fat content was significantly associated with an increased drug transfer into breast milk (+28% for SCIT and +18% for SDCIT when fat amount doubles from 3.1 to 6.2 g/100 mL). Simulations suggested that an exclusively breastfed infant would ingest daily through breast milk 3.3% of the weight-adjusted maternal SCIT dose on average. CONCLUSION: The moderate between-subject variability in milk concentration of SCIT and the limited exposure to escitalopram through breast milk observed provide reassurance for treated mothers of breastfed healthy infants.
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Citalopram/farmacocinética , Leite Humano , Inibidores Seletivos de Recaptação de Serotonina/farmacocinética , Animais , Aleitamento Materno , Feminino , Humanos , Lactente , Leite Humano/metabolismo , Preparações Farmacêuticas , Gravidez , Estudos ProspectivosRESUMO
BACKGROUND: Very preterm (VPT) infants are at risk for neurodevelopmental impairments and early clinical findings such as transient tone anomalies (TTA) might represent potential predictive indicators. AIMS: The aims of this study were to assess 1) the prevalence of TTA at 6 months corrected age in a population of VPT infants, 2) the association with term-equivalent age (TEA) brain MRI and 3) the neurodevelopmental outcome at 18 months corrected age. STUDY DESIGN AND SUBJECTS: A prospective case-control cohort of 103 VPT infants (<29 weeks of gestation) was followed up at 6 months and classified into TTA+ or TTA-. TTA+ was defined by the presence of ≥2 criteria among anomalies of posture, anomalies of tone and hyperreflexia. OUTCOME MEASURES: Conventional and diffusion-weighted MRIs at TEA were analyzed according to a semi-quantitative MRI scoring system and apparent diffusion coefficients (ADC) and fractional anisotropy (FA) were measured in frontal, occipital white matter and posterior limb of the internal capsule (PLIC). Neurodevelopment was assessed at 18 months using Bayley-II scales (Psychomotor Developmental Index: PDI; Mental Developmental Index: MDI). RESULTS: TTA+ infants represented 29.1% of the total population. They had: 1) significantly higher ADC values in 3 regions of interest (p < 0.001), 2) significant lower FA in the PLIC (p < 0.001), and 3) significant lower PDI score (p < 0.05). No differences were observed regarding MDI scores. Interaction of TTA by cerebellum score was related to lower MDI scores. CONCLUSIONS: In VPT infants, TTA at 6 months and/or structural brain abnormality at TEA are associated with poorer neurodevelopmental outcome at 18 months.
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Encéfalo/diagnóstico por imagem , Distúrbios Distônicos/epidemiologia , Lactente Extremamente Prematuro/fisiologia , Doenças do Prematuro/epidemiologia , Transtornos do Neurodesenvolvimento/epidemiologia , Feminino , Humanos , Lactente , Lactente Extremamente Prematuro/crescimento & desenvolvimento , Recém-Nascido , Imageamento por Ressonância Magnética , MasculinoRESUMO
INTRODUCTION: Orbitofrontal reality filtering (ORFi) is a memory mechanism that distinguishes whether a thought is relevant to present reality or not. In adults, it is mediated by the orbitofrontal cortex (OFC). This region is still not fully developed in preteenagers, but ORFi is already active from age 7. Here, we probe the neural correlates of ORFi in early adolescents, hypothesizing that OFC mediates the sense of reality in this population. METHODS: Functional magnetic resonance images (fMRI) were acquired in 22 early adolescents during a task composed of two runs: run 1 measuring recognition capacity; run 2 measuring ORFi; each containing two types of images (conditions): distractors (D: images seen for the first time in the current run) and targets (T: images seen for the second time in the current run). Group region of interest (ROI) analysis was performed in a flexible factorial design with two factors (run and condition) using SPM12. RESULTS: We found significant main effects for the experimental run and condition. The bilateral OFC activation was higher during ORFi than during the first run. Additionally, the OFC was more active while processing distractors than targets. CONCLUSION: These results confirm, for the first time, the role of OFC in reality filtering in early adolescents.
Assuntos
Memória/fisiologia , Córtex Pré-Frontal/fisiologia , Reconhecimento Psicológico/fisiologia , Adolescente , Criança , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Estimulação Luminosa , Córtex Pré-Frontal/diagnóstico por imagemRESUMO
Prematurity disrupts brain maturation by exposing the developing brain to different noxious stimuli present in the neonatal intensive care unit (NICU) and depriving it from meaningful sensory inputs during a critical period of brain development, leading to later neurodevelopmental impairments. Musicotherapy in the NICU environment has been proposed to promote sensory stimulation, relevant for activity-dependent brain plasticity, but its impact on brain structural maturation is unknown. Neuroimaging studies have demonstrated that music listening triggers neural substrates implied in socio-emotional processing and, thus, it might influence networks formed early in development and known to be affected by prematurity. Using multi-modal MRI, we aimed to evaluate the impact of a specially composed music intervention during NICU stay on preterm infant's brain structure maturation. 30 preterm newborns (out of which 15 were exposed to music during NICU stay and 15 without music intervention) and 15 full-term newborns underwent an MRI examination at term-equivalent age, comprising diffusion tensor imaging (DTI), used to evaluate white matter maturation using both region-of-interest and seed-based tractography approaches, as well as a T2-weighted image, used to perform amygdala volumetric analysis. Overall, WM microstructural maturity measured through DTI metrics was reduced in preterm infants receiving the standard-of-care in comparison to full-term newborns, whereas preterm infants exposed to the music intervention demonstrated significantly improved white matter maturation in acoustic radiations, external capsule/claustrum/extreme capsule and uncinate fasciculus, as well as larger amygdala volumes, in comparison to preterm infants with standard-of-care. These results suggest a structural maturational effect of the proposed music intervention on premature infants' auditory and emotional processing neural pathways during a key period of brain development.