RESUMO
In France, the most pessimistic estimates put the prevalence of neurodevelopmental disorders (NDD) at 15 % of births. The two largest populations of newborns at highest risk of NDD are premature babies and babies born into siblings with one or more infants who already have an autism spectrum disorder or another NDD. The high prevalence of these disorders justifies a health promotion policy, centred on the child and his or her family. Prevention is based on the early identification of high-risk factors, by informing families and training pregnancy and early childhood professionals, and implementing perinatal prevention protocols for high-risk newborns (antenatal corticosteroid therapy and magnesium sulfate for women at risk of preterm delivery before 32 weeks, developmental care, therapeutic hypothermia for full-term infants with early neonatal encephalopathy presumed to be anoxic). Preventing the severity of NDD depends on their early identification, as early as possible in the highest plastic "1000 days" developmental window, a smooth flow of diagnosis and care for mothers and children, and the establishment of an ecosystem that includes multi-modal early intervention, at the best in multi-disciplinary teams such as the early medical and social action centres, support for families through guidance programs and inclusion in the community, first in day-care centers and then in nursery schools.
Assuntos
Transtornos do Neurodesenvolvimento , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Gravidez , França , Recém-Nascido Prematuro , Transtornos do Neurodesenvolvimento/prevenção & controle , Transtornos do Neurodesenvolvimento/epidemiologia , Neuroproteção , Fatores de RiscoRESUMO
PURPOSE: The purpose of this study was to identify in the EPIRMEX cohort the correlations between MRI brain metrics, including diffuse excessive high signal intensities (DEHSI) obtained with an automated quantitative method and neurodevelopmental outcomes at 2 years. MATERIALS AND METHODS: A total of 390 very preterm infants (gestational age at birth≤32 weeks) who underwent brain MRI at term equivalent age at 1.5T (n=338) or 3T (n=52) were prospectively included. Using a validated algorithm, automated metrics of the main brain surfaces (cortical and deep gray matter, white matter, cerebrospinal fluid) and DEHSI with three thresholds were obtained. Linear adjust regressions were performed to assess the correlation between brain metrics with the ages and stages questionnaire (ASQ) score at 2 years. RESULTS: Basal ganglia and thalami, cortex and white matter surfaces positively and significantly correlated with the global ASQ score. For all ASQ sub-domains, basal ganglia and thalami surfaces significantly correlated with the scores. DEHSI was present in 289 premature newborns (74%) without any correlation with the ASQ score. Metrics of DEHSI were greater at 3T than at 1.5T. CONCLUSION: Brain MRI metrics obtained in our multicentric cohort correlate with the neurodevelopmental outcome at 2 years of age. The quantitative detection of DEHSI is not predictive of adverse outcomes. Our automated algorithm might easily provide useful predictive information in daily practice.
Assuntos
Benchmarking , Doenças do Prematuro , Encéfalo/diagnóstico por imagem , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Imageamento por Ressonância MagnéticaRESUMO
INTRODUCTION: SMG9 deficiency is an extremely rare autosomal recessive condition originally described in three patients from two families harboring homozygous truncating SMG9 variants in a context of severe syndromic developmental disorder. To our knowledge, no additional patient has been described since this first report. METHODS: We performed exome sequencing in a patient exhibiting a syndromic developmental delay and in her unaffected parents and report the phenotypic features. RESULTS: Our patient presented with a syndromic association of severe global developmental delay and diverse malformations, including cleft lip and palate, facial dysmorphic features, brain abnormalities, heart defect, growth retardation, and severe infections. She carried a novel SMG9 homozygous variant NM_019108.3:c.1177C>T, p.(Gln393*), while her unaffected parents were both heterozygous. CONCLUSIONS: We confirm that bi-allelic truncating SMG9 variants cause a severe developmental syndrome including brain and heart malformations associated with facial dysmorphic features, severe growth and developmental delay with or without ophthalmological abnormalities, severe feeding difficulties, and life-threatening infections.
Assuntos
Deficiências do Desenvolvimento/diagnóstico , Deficiências do Desenvolvimento/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Peptídeos e Proteínas de Sinalização Intracelular/genética , Mutação , Alelos , Encéfalo/anormalidades , Encéfalo/diagnóstico por imagem , Pré-Escolar , Consanguinidade , Feminino , Estudos de Associação Genética/métodos , Homozigoto , Humanos , Linhagem , Fenótipo , SíndromeRESUMO
BACKGROUND: Intraventricular hemorrhage (IVH) is a frequent complication in extreme and very preterm births. Despite a high risk of death and impaired neurodevelopment, the precise prognosis of infants with IVH remains unclear. The objective of this study was to evaluate the rate and predictive factors of evolution to post hemorrhagic hydrocephalus (PHH) requiring a shunt, in newborns with IVH and to report their neurodevelopmental outcomes at 2 years of age. METHODS: Among all preterm newborns admitted to the department of neonatalogy at Rouen University Hospital, France between January 2000 and December 2013, 122 had an IVH and were included in the study. Newborns with grade 1 IVH according to the Papile classification were excluded. RESULTS: At 2-year, 18% (n = 22) of our IVH cohort required permanent cerebro spinal fluid (CSF) derivation. High IVH grade, low gestational age at birth and increased head circumference were risk factors for PHH. The rate of death of IVH was 36.9% (n = 45). The rate of cerebral palsy was 55.9% (n = 43) in the 77 surviving patients (49.4%). Risk factors for impaired neurodevelopment were high grade IVH and increased head circumference. CONCLUSION: High IVH grade was strongly correlated with death and neurodevelopmental outcome. The impact of an increased head circumference highlights the need for early management. CSF biomarkers and new medical treatments such as antenatal magnesium sulfate have emerged and could predict and improve the prognosis of these newborns with PHH.
Assuntos
Hemorragia Cerebral/complicações , Hidrocefalia/etiologia , Transtornos do Neurodesenvolvimento/etiologia , Paralisia Cerebral/epidemiologia , Derivações do Líquido Cefalorraquidiano/estatística & dados numéricos , Pré-Escolar , Epilepsia/etiologia , Feminino , Seguimentos , França , Idade Gestacional , Cabeça/anatomia & histologia , Transtornos da Audição/etiologia , Mortalidade Hospitalar , Humanos , Hidrocefalia/complicações , Hidrocefalia/terapia , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Unidades de Terapia Intensiva Neonatal , Transtornos do Desenvolvimento da Linguagem/etiologia , Masculino , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Transtornos da Visão/etiologiaRESUMO
Neurodevelopmental outcome in children with agenesis of the corpus callosum (ACC) is correlated with the presence or absence of associated brain abnormalities. Indeed, neurodevelopmental outcome shows severe disabilities when the ACC is not isolated whereas in isolated forms, the neurologic development is mainly normal. Contrary to data in several published studies, the prognosis remains uncertain even in isolated forms, which may lead in France to medical termination of pregnancy. OBJECTIVE: To evaluate long-term neurodevelopmental outcome in children with prenatally diagnosed isolated ACC. DESIGN, SETTING AND PARTICIPANTS: This is a follow-up study conducted in Normandy (France). It included a cohort of 25 children born between January 1991 and June 2016, with a prenatal diagnosis of isolated ACC and who were followed for at least two years. RESULTS: The average follow-up was 8±5years. ACC was complete in 17 patients (68%), partial in 5 (20%) and hypoplastic in 3 (12%). Whereas global motor development was normal in each case, normal neurodevelopmental outcome or mild disabilities occurred in 88% children and moderate/severe neuro-disabilities were present in 12% of children. Wechsler Intelligence Scale for Children-IV evaluations and Intellectual Total Quotients were within normal range, but we observed lower scores in verbal comprehension, social judgment, executive functions. A lower score in morphosyntax was observed among 52% of children with oral language disorders. CONCLUSIONS: Neurodevelopmental outcome was favorable in most of our patients with isolated ACC, but mild learning disabilities emerged in older children. Long-term follow-up until school age is essential to provide early diagnosis and appropriate care support.
Assuntos
Agenesia do Corpo Caloso/diagnóstico , Agenesia do Corpo Caloso/etiologia , Deficiências do Desenvolvimento/etiologia , Adolescente , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Masculino , Gravidez , Diagnóstico Pré-Natal , Psicometria/métodos , Distúrbios da Fala/etiologia , Escalas de WechslerRESUMO
OBJECTIVE: Our aim is to assess the neurodevelopmental outcome of children with a prenatal diagnosis of apparently isolated severe ventriculomegaly (SVM). METHOD: This is a retrospective cohort study from 1994 to 2011. We included fetuses with unilateral or bilateral ventriculomegaly equal to or greater than 15 mm at prenatal ultrasound and confirmed by magnetic resonance imaging, whose parents chose continuation of pregnancy past 22 weeks, and with no associated findings at diagnosis (i.e. no brain malformation or cerebral lesions, normal karyotype, no other congenital abnormalities by ultrasound, and negative toxoplasma, rubella, cytomegalovirus, and herpes test. Children were followed up for at least 2 years. Children were classified into three groups: normal, moderate, or severe abnormalities according to psychomotor developmental stages and/or a visual or hearing impairment and/or behavioral disorders. RESULTS: Twenty-one patients fulfilled the study criteria. SVM was diagnosed at an average gestational age of 30 weeks (range 22-37 weeks). Head circumference was >95th centile in 39% of them. The etiology of SVM was intraventricular hemorrhage in 6 (29%), stenosis of the aqueduct of Sylvius in 3 (14%), and undetermined in 12 (57%). Neurosurgery was performed in four infants, and ventriculoperitoneal shunts were inserted in three. At a mean age at last follow-up of 8.4 years, neurodevelopmental outcome was normal in 62% and moderate and severely impaired in 14% and 24% of children, respectively. There was no association between neurologic outcome and severity of ventricular dilation at prenatal imaging, gestational age at initial diagnosis of SVM, or etiology of the ventricular dilatation. CONCLUSION: The majority of children with apparently isolated SVM show normal neurodevelopmental outcome. No prenatal risk factor identify cases at higher risk for severely abnormal neurologic outcome. © 2017 John Wiley & Sons, Ltd.
Assuntos
Hidrocefalia/complicações , Transtornos do Neurodesenvolvimento/etiologia , Adulto , Criança , Desenvolvimento Infantil , Feminino , França/epidemiologia , Humanos , Hidrocefalia/diagnóstico por imagem , Hidrocefalia/epidemiologia , Recém-Nascido , Sistema Nervoso/crescimento & desenvolvimento , Transtornos do Neurodesenvolvimento/epidemiologia , Gravidez , Estudos Retrospectivos , Ultrassonografia Pré-NatalRESUMO
OBJECTIVE: To investigate alteration in 2-year neurological/behavioral outcomes of very preterm infants born in a French level three neonatal intensive care unit. METHODS: We conducted a prospective, comparative study of very preterm infants born before 33 weeks' gestation at 5-year intervals in 2000, 2005 and 2010 at Rouen University Hospital. Neonatal mortality/morbidities, ante- and neonatal treatments, and at age 2 years motor, cognitive and behavioral data were collected by standardized questionnaires. RESULTS: We included 536 very preterm infants. Follow-up rates at two years old were 78% in 2000, 93% in 2005 and 92% in 2010 respectively. No difference in gestational age, birthweight, neonatal mortality/morbidities was observed except a decrease in low grade subependymal/intraventricular hemorrhages. Care modifications concerned use of antenatal magnesium sulfate, breast-feeding and post-natal corticosteroid therapy. Significant improvement in motor outcome and dramatic decrease in cerebral palsy rates (12% in 2000, 6% in 2005, 1% in 2010, p<0.001) were observed, as were improvements in feeding behavior. Although a non significant difference to better psychosocial behavior was reported, there was no difference in cognitive outcome. CONCLUSIONS: Improvement in neuromotor outcome and behavior was reported. This could be due to multiple modifications in care: including administration of magnesium sulfate to women at risk of preterm birth, increase in breast-feeding, decrease in low grade subependymal/intraventricular hemorrhages, and decrease in post-natal corticosteroid therapy, all of which require further investigation in other studies. Extended follow-up until school age is mandatory for better detection of cognitive, learning and behavioral disorders.
Assuntos
Desenvolvimento Infantil/fisiologia , Cognição/fisiologia , Comportamento Alimentar/fisiologia , Lactente Extremamente Prematuro/fisiologia , Atividade Motora/fisiologia , Pré-Escolar , Feminino , Humanos , Masculino , Estudos ProspectivosRESUMO
AIM: To compare neonatal and 2-year outcomes in very premature infants born 5 years apart. METHODS: Prospective observational study of infants born before 33 weeks' gestation in 2000 or 2005 admitted to a neonatal intensive care unit in France. We collected perinatal data and evaluated motor, cognitive, neurosensory and behavioural outcomes at 2 years of age. RESULTS: We included 170 infants in 2000 and 173 in 2005. The significant differences in neonatal outcomes were decreases in postnatal corticosteroid use and in percentage of infants with head circumference below the 3rd percentile on days 7 (25% vs. 13%) and 30 (30% vs. 17%). At 2 years of age, rates of follow-up were 87% in 2000 and 94% in 2005. The cerebral palsy rate was 6% in both cohorts. The overall rate of motor disabilities diminished from 30% (41/137) to 18% (26/142), and the rate of mild motor disabilities decreased from 24% to 12%. Rates of cognitive, behavioural and neurosensorial impairments were similar. CONCLUSION: Between 2000 and 2005, motor impairments at 2 years of age diminished in very preterm children (but not cerebral palsy rates). We observed a reduced use of postnatal corticosteroids and a decreased percentage of neonates with head circumference below the third percentile.