Neurodevelopment in Children Exposed to Zika Virus: What Are the Consequences for Children Who Do Not Present with Microcephaly at Birth?

Abstract

The relation of Zika virus (ZIKV) with microcephaly is well established. However, knowledge is lacking on later developmental outcomes in children with evidence of maternal ZIKV infection during pregnancy born without microcephaly. The objective of this analysis is to investigate the impact of prenatal exposure to ZIKV on neuropsychomotor development in children without microcephaly. We evaluated 274 children including 235 ZIKV exposed and 39 controls using the Bayley-III Scales of Infant and Toddler Development (BSIDIII) and neurological examination. We observed a difference in cognition with a borderline p-value (p = 0.052): 9.4% of exposed children and none of the unexposed control group had mild to moderate delays. The prevalence of delays in the language and motor domains did not differ significantly between ZIKV-exposed and unexposed children (language: 12.3% versus 12.8%; motor: 4.7% versus 2.6%). Notably, neurological examination results were predictive of neurodevelopmental delays in the BSIDIII assessments for exposed children: 46.7% of children with abnormalities on clinical neurological examination presented with delay in contrast to 17.8% among exposed children without apparent neurological abnormalities (p = 0.001). Overall, our findings suggest that relative to their unexposed peers, ZIKV-exposed children without microcephaly are not at considerably increased risk of neurodevelopmental impairment in the first 42 months of life, although a small group of children demonstrated higher frequencies of cognitive delay. It is important to highlight that in the group of exposed children, an abnormal neuroclinical examination may be a predictor of developmental delay. The article contributes to practical guidance and advances our knowledge about congenital Zika.

Neurodevelopmental outcomes in congenital and perinatal infections

“…A study in the West Indies reported that children exposed to ZIKV during pregnancy without CZS had similar rates of abnormal neurodevelopment between 22 and 30 months of age compared with ZIKV-unexposed peers [78 ▪ ]. In a longitudinal Brazilian study of 235 normocephalic children exposed to ZIKV during pregnancy assessed using the Bayley-III between 6 and 42 months, 9.4, 12.3, and 4.7% showed mild–moderate delays in the cognitive, language, and motor scores, respectively; however, they did not find increased developmental concerns compared with 39 unexposed children [79 ▪ ]. Differences in duration of follow-up, number of cases and controls, neurodevelopmental outcome measures, and social–economic or environmental factors may be reasons for different findings.…”

Feeding characteristics and growth among children with prenatal exposure to Zika virus with and without microcephaly in the microcephaly epidemic research group pediatric cohort

“…In addition to their role in causing swallowing disorders, ZIKV-related neurological impairments may also lead to challenges with introducing solid foods and with acquiring motor skills for performing the eating-related tasks required to attain an appropriate diet. Some recent studies have suggested that the greater the severity of ZIKV-related microcephaly, the greater the impairment of neurodevelopment in children [ 3 , 4 ].…”

Does Intra-Uterine Exposure to the Zika Virus Increase Risks of Cognitive Delay at Preschool Ages? Findings from a Zika-Exposed Cohort from Grenada, West Indies

“…However, not all children with prenatal ZIKV exposure are at risk. Although ZIKV targets neural stem cells in the developing brain, neurological manifestations are not apparent at birth in the majority of ZIKV-exposed children [ 3 , 4 ].…”