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.
Highlights
Chikungunya virus (CHIKV), a re-emerging alphavirus transmitted by Aedes mosquitoes, has been responsible for major epidemics in Eastern Africa, numerous islands in the Indian Ocean, India and Sri Lanka between 2004 and 2007, before spreading for the first time into the Italian province of Emilia-Romagna [1], where it provoked, in July 2007, a three-month outbreak of 257 cases [2]
Our findings suggest that CHIKV infection, acquired in the perinatal period, can cause severe disease with lifelong expected disability
Exposure definition CHIKV perinatal mother-to-child infection (p-CHIKV infection) was identified for the infants of mothers infected during pregnancy with a positive reverse transcriptase polymerase chain reaction (RT-PCR) result and/or presence of CHIKV-specific MAC-ELISA IgM antibodies before day 10
Summary
Chikungunya virus (CHIKV), a re-emerging alphavirus transmitted by Aedes mosquitoes, has been responsible for major epidemics in Eastern Africa, numerous islands in the Indian Ocean, India and Sri Lanka between 2004 and 2007, before spreading for the first time into the Italian province of Emilia-Romagna [1], where it provoked, in July 2007, a three-month outbreak of 257 cases [2]. Little is known about the neurocognitive outcome in children exposed to perinatal mother-to-child Chikungunya virus (p-CHIKV) infection
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