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.
Highlights
Mothers from the control group had a higher level of education and the children were approximately 4 months older at the time of the BSIDIII assessment
We present the results from neurodevelopmental evaluation of one of the largest samples ever studied relative to children exposed to Zika virus (ZIKV) without microcephaly compared to a control group without prenatal ZIKV exposure
The neuroclinical examination was predictive of neurodevelopment delay and showed significant association with the BSIDIII for the language and motor function domains
Summary
The link of Zika virus (ZIKV) to neurological impairment was described based on the outbreak of congenital anomalies observed in Brazil beginning in October 2015 [1,2,3].The short-term risks of congenital ZIKV infections are already known and the impairment of neurodevelopment is evident in children with moderate to severe microcephaly [4,5,6].the risk of developmental delays in children with evidence of maternal ZIKV infection during pregnancy born without microcephaly remains unknown [7,8,9].Recognizing that congenital ZIKV infections may result in later-life consequences for children born ‘apparently asymptomatic’ for Congenital Zika Syndrome (CZS), the Microcephalic Epidemic Research Group (MERG) followed up a cohort of exposed children in order to identify abnormalities detected at later ages [10]. The short-term risks of congenital ZIKV infections are already known and the impairment of neurodevelopment is evident in children with moderate to severe microcephaly [4,5,6]. The risk of developmental delays in children with evidence of maternal ZIKV infection during pregnancy born without microcephaly remains unknown [7,8,9]. This paper reports on neurological and neurodevelopmental findings in children with no abnormal findings identified at birth, such as microcephaly, born to mothers who had evidence of ZIKV infection in pregnancy. In a previously published study, the MERG conducted a neurodevelopmental assessment with a screening instrument and found a gradient of risk of developmental delay according to head circumference. We sought to expand the assessment by using the Bayley-III Scales of Infant and Toddler Development (BSIDIII), which is a more specific instrument for evaluating cognitive, language, and motor development [12,13]
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