title: Neurocognitive outcome of children exposed to perinatal mother-to-child Chikungunya virus infection: the CHIMERE cohort study on Reunion Island.
abstract: BACKGROUND
  Little is known about the neurocognitive outcome in children exposed to perinatal mother-to-child Chikungunya virus (p-CHIKV) infection.
  
  
  METHODS
  The CHIMERE ambispective cohort study compared the neurocognitive function of 33 p-CHIKV-infected children (all but one enrolled retrospectively) at around two years of age with 135 uninfected peers (all enrolled prospectively). Psychomotor development was assessed using the revised Brunet-Lezine scale, examiners blinded to infectious status. Development quotients (DQ) with subscores covering movement/posture, coordination, language, sociability skills were calculated. Predictors of global neurodevelopmental delay (GND, DQ ≤ 85), were investigated using multivariate Poisson regression modeling. Neuroradiologic follow-up using magnetic resonance imaging (MRI) scans was proposed for most of the children with severe forms.
  
  
  RESULTS
  The mean DQ score was 86.3 (95%CI: 81.0-91.5) in infected children compared to 100.2 (95%CI: 98.0-102.5) in uninfected peers (P<0.001). Fifty-one percent (n = 17) of infected children had a GND compared to 15% (n = 21) of uninfected children (P<0.001). Specific neurocognitive delays in p-CHIKV-infected children were as follows: coordination and language (57%), sociability (36%), movement/posture (27%). After adjustment for maternal social situation, small for gestational age, and head circumference, p-CHIKV infection was found associated with GND (incidence rate ratio: 2.79, 95%CI: 1.45-5.34). Further adjustments on gestational age or breastfeeding did not change the independent effect of CHIKV infection on neurocognitive outcome. The mean DQ of p-CHIKV-infected children was lower in severe encephalopathic children than in non-severe children (77.6 versus 91.2, P<0.001). Of the 12 cases of CHIKV neonatal encephalopathy, five developed a microcephaly (head circumference <-2 standard deviations) and four matched the definition of cerebral palsy. MRI scans showed severe restrictions of white matter areas, predominant in the frontal lobes in these children.
  
  
  CONCLUSIONS
  The neurocognitive outcome of children exposed to perinatal mother-to-child CHIKV infection is poor. Severe CHIKV neonatal encephalopathy is associated with an even poorer outcome.
authors.affiliation: CHU de La Réunion Saint-Denis/Saint-Pierre, La Réunion, France; INSERM CIC-EC (CIE2), Saint-Pierre, La Réunion, France; INSERM UMRS 953, "Epidemiological Research Unit on Perinatal Health and Women and Children Health", UPMC Université Paris 6, Paris, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Gérardin
authors.affiliation: CHU de La Réunion Saint-Denis/Saint-Pierre, La Réunion, France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Sampériz
authors.affiliation: CHU de La Réunion Saint-Denis/Saint-Pierre, La Réunion, France; INSERM CIC-EC (CIE2), Saint-Pierre, La Réunion, France; GRI, Research Group on Immunopathology and Infection, EA4517, Université de La Réunion, INSERM UMRS 945 "Immunity and Infection" Saint-Denis, La Réunion, France.
authors.forename: Duksha
authors.initials: D
authors.lastname: Ramful
authors.affiliation: CHU de La Réunion Saint-Denis/Saint-Pierre, La Réunion, France.
authors.forename: Brahim
authors.initials: B
authors.lastname: Boumahni
authors.affiliation: CHU de La Réunion Saint-Denis/Saint-Pierre, La Réunion, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Bintner
authors.affiliation: CHU de La Réunion Saint-Denis/Saint-Pierre, La Réunion, France.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Alessandri
authors.affiliation: CHU de La Réunion Saint-Denis/Saint-Pierre, La Réunion, France.
authors.forename: Magali
authors.initials: M
authors.lastname: Carbonnier
authors.affiliation: CHU de La Réunion Saint-Denis/Saint-Pierre, La Réunion, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Tiran-Rajaoefera
authors.affiliation: Centre Hospitalier Gabriel Martin, Saint-Paul, La Réunion, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Beullier
authors.affiliation: Centre Hospitalier de l'Est Réunion, Saint-Benoît, La Réunion, France.
authors.forename: Irénée
authors.initials: I
authors.lastname: Boya
authors.affiliation: Clinique Sainte-Clotilde, Sainte-Clotilde, La Réunion, France.
authors.forename: Tahir
authors.initials: T
authors.lastname: Noormahomed
authors.affiliation: Clinique Durieux, Le Tampon, La Réunion, France; Centre d'Action Médico-Sociale Précoce (CAMSP), Saint-Louis, La Réunion, France.
authors.forename: Jocelyn
authors.initials: J
authors.lastname: Okoï
authors.affiliation: INSERM CIC-EC (CIE2), Saint-Pierre, La Réunion, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Rollot
authors.affiliation: CHU de La Réunion Saint-Denis/Saint-Pierre, La Réunion, France.
authors.forename: Liliane
authors.initials: L
authors.lastname: Cotte
authors.affiliation: CHU de La Réunion Saint-Denis/Saint-Pierre, La Réunion, France.
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Jaffar-Bandjee
authors.affiliation: CHU de La Réunion Saint-Denis/Saint-Pierre, La Réunion, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Michault
authors.affiliation: INSERM CIC-EC (CIE2), Saint-Pierre, La Réunion, France.
authors.forename: François
authors.initials: F
authors.lastname: Favier
authors.affiliation: INSERM UMRS 953, "Epidemiological Research Unit on Perinatal Health and Women and Children Health", UPMC Université Paris 6, Paris, France.
authors.forename: Monique
authors.initials: M
authors.lastname: Kaminski
authors.affiliation: CHU de La Réunion Saint-Denis/Saint-Pierre, La Réunion, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Fourmaintraux
authors.affiliation: INSERM UMRS 953, "Epidemiological Research Unit on Perinatal Health and Women and Children Health", UPMC Université Paris 6, Paris, France; Poitiers University Hospital, Poitiers, France; INSERM CIC-P 0802, Poitiers, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Fritel
mesh_terms: D065632:Chikungunya Fever / Q000453:epidemiology / Q000635:transmission / Q000821:virology; D002646:Chikungunya virus; D002675:Child, Preschool; D002658:Developmental Disabilities / Q000453:epidemiology / Q000821:virology; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical / Q000706:statistics & numerical data*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000453:epidemiology / Q000821:virology; D012189:Retrospective Studies; D017508:Reunion / Q000453:epidemiology