Neurocognitive Outcome of Children Exposed to Perinatal Mother-to-Child Chikungunya Virus Infection: The CHIMERE Cohort Study on Reunion Island

Abstract

BackgroundLittle is known about the neurocognitive outcome in children exposed to perinatal mother-to-child Chikungunya virus (p-CHIKV) infection.MethodsThe 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.ResultsThe 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.ConclusionsThe 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.

Reporte de caso de transmisión vertical de la infección por virus chikungunya

“…Long-term follow-up of these patients with perinatal chikungunya virus infection has been shown to have an increased risk of global neurodevelopmental delay, especially those with encephalopathy in the neonatal period. The predominant alterations are coordination and language 10 .…”

Chikungunya virus: epidemiology, replication, disease mechanisms, and prospective intervention strategies

“…However, maternal-fetal transmission can occur intrapartum, which results in high rates of infant morbidity (12,13). Historically, CHIKV has been endemic in tropical and subtropical regions of sub-Saharan Africa and Southeast Asia, where two distinct CHIKV transmission cycles exist.…”

Emerging Role of Zika Virus in Adverse Fetal and Neonatal Outcomes

“…After adjustment for maternal social situation, IUGR, and head circumference, CHIKV infection was found to be associated with global neurodevelopmental delay (incidence rate ratio, 2.79; 95% CI, 1.45 to 5.34). Twelve infants presented with CHIKV neonatal encephalopathy, and five developed microcephaly (252).…”