Long-term neurological and neurodevelopmental outcome of neonatal listeriosis in France: a prospective, matched, observational cohort study.

BACKGROUND: Maternal-neonatal listeriosis is a rare and serious infection. The long-term outcome of surviving infants with early-onset or late-onset listeriosis remains unknown. We aimed to determine the long-term neurological and neurodevelopmental outcome of neonatal listeriosis. METHODS: In this prospective, matched, observational cohort study, we evaluated children born with microbiologically confirmed maternal-neonatal listeriosis in the French MONALISA cohort. At age 5 years, children underwent neurological and neurodevelopmental assessments of sensory deficits, executive function, adaptive behaviour, and cognitive and motor coordination function. The cognitive domain was assessed using the French version of the Wechsler Preschool and Primary Scale of Intelligence, fourth edition, and scored by Full Scale Intelligence Quotient (FSIQ). The motor domain was assessed by physical examination designed to screen for cerebral palsy and developmental coordination disorder. Executive functioning was assessed using the statue and inhibition subtests of Neuropsychological Assessment, second version. The sensory domain was assessed by parental interview, medical report, and clinical assessment. Adaptive behaviour was measured using the Vineland-II behaviour scale from parent-reported assessments of functional communication, socialisation, daily living, and motor skills. Results were compared with gestational age-matched children from two national prospective cohorts: EPIPAGE-2 (preterm infants) and ELFE (term infants from a general population of infants >32 weeks gestation). This study is registered with ClinicalTrials.gov (NCT02580812). FINDINGS: Of 59 children who were alive and eligible to participate in the study, 53 (median age 5 years, IQR 5-6) were enrolled for neurodevelopmental assessments between Oct 26, 2016, and Oct 29, 2019. Of 53 children, 31 (58%) had been born preterm, 22 (42%) had early-onset systemic infection, 18 (34%) had early-onset non-systemic infection, and six (11%) had late-onset systemic infection, all with meningitis. 29 (66%) of 44 children, in whom neurodevelopmental disabilities scores were available, developed at least one disability; eight (18%) children had severe neurodevelopmental disabilities. Of four children with late-onset infection and in whom neurodevelopmental disabilities scores were available, three developed at least one neurodevelopmental disability. Neurological and neurodevelopmental outcomes of children with neonatal listeriosis did not differ from those of gestational age-matched control children without infection (relative risk [RR] of at least one disability 0·99 [95% CI 0·65-1·51; p=0·97]; RR of FSIQ less than -1 SD 0·92 [0·54-1·54; p=0·74]). INTERPRETATION: These results highlight the burden of persistent disability and dominant contribution of prematurity to long-term outcomes in children born with neonatal listeriosis. The findings support the implementation of systematic long-term screening and provision of tailored education and special needs support. FUNDING: Institut Pasteur, Inserm, French Public Health Agency, Contrat de Recherche Clinique, and Assistance Publique-Hôpitaux de Paris.

Autism spectrum disorder and cognitive profile in children with Dravet syndrome: Delineation of a specific phenotype.

OBJECTIVE: We aimed to assess a cohort of young patients with Dravet syndrome (DS) for intellectual disability (ID) and autism spectrum disorder (ASD) using standardized tools and parental questionnaires to delineate their specific profiles. METHODS: We included 35 patients with DS aged 24 months to 7 years, excluding patients with a developmental age (DA) <18 months (n = 5). We performed specific tests adapted for ID (Psychoeducational Profile, Third Edition [PEP-3]), in addition to the Child Development Inventory (CDI) and Vineland Adaptive Behavior Scales, Second Edition (VABS-II) questionnaires. We used 2 standardized tools for ASD: the Autism Diagnostic Observation Schedule, Second Edition (ADOS-2) and the Autism Diagnostic Interview-Revised (ADI-R). We compared the with parental questionnaires and the VABS-II, and with ASD characteristics. RESULTS: PEP-3 subscales showed pathologic development in all but one patient (97%): ID in 23 of 30 (77%), and borderline cognitive functioning in 6 of 30 (22%). Eleven patients (39%) had ASD and 2 (7%) had a Social Communication Disorder (SCD) diagnosis. We found no difference between PEP-3 and CDI categorization except for fine motor skills. We found significant negative correlations between ADOS-2 and PEP-3 for the majority of scores. For patients aged older than 50 months, 2 groups emerged (ASD/no ASD) with significant difference in DA. The logistic regression for ASD diagnosis explained by VABS-II showed a significant effect for Socialization, Motor Skills, and Adaptive Behavior. SIGNIFICANCE: We found a high prevalence of ID in patients with DS. ID is characterized by expressive and comprehensive communication deficits in addition to visuospatial difficulties. ASD showed a specific profile with a relative preservation of social skills, emphasizing a possible underdiagnosis. Parental questionnaires can provide a good assessment of cognitive profile and might allow the difficulty of addressing cognitive scales in DS to be overcome. The profile of ID and ASD should help to establish early adapted rehabilitation programs and emphasizes the global need for care beyond seizures in DS and other developmental epileptic encephalopathies.