Impaired Brain Growth in Children Perinatally Infected With Chikungunya

BACKGROUND: Chikungunya neonatal encephalitis can cause microcephaly. However, little is known about brain growth following chikungunya perinatal infection. We sought to evaluate and explore head growth (HG) outcomes after perinatal infection with the chikungunya virus. METHODS: In a child cohort, we compared at adolescence age HG, a proxy indicator of brain growth, and HG dynamics by infectious status. In an adult cohort, we searched for differentially expressed genes (DEGs) known to be related to subcortical brain volumes and head size to generate mechanistic hypotheses that could underly the relationship between chikungunya perinatal infection and brain growth. RESULTS: Cohort 1. Forty-two adolescent children (6 encephalitic, 13 nonencephalitic, 23 noninfected [NI]) were enrolled between January 2020 and January 2021. Head circumference was lower in infected than in NI children regardless of chikungunya presentation. HG showed a loss of percentiles in infected children, and a growth gain in the NI. This observation persisted when we compared nonencephalitic/nonmicrocephalic to NI children after excluding the six encephalitic children. Cohort 2. In the adult cohort, we identified 22 DEGs related to delayed myelination, postnatal microcephaly, hypomyelination, and leukoencephalopathy in the bulk transcriptome of peripheral blood mononuclear cells from 224 infected subjects recruited between August 2018 and October 2020. The relevance of these DEGs for neurologic involvement in chronic chikungunya was supported through pathway analysis. CONCLUSIONS: These findings could support the monitoring of neurocognitive milestones in all children perinatally infected with chikungunya and open up new avenues of research into the neuropathogenesis of chikungunya neonatal encephalitis.