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

Abstract

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.