Abstract
ObjectiveTo describe the neurological and neurodevelopmental outcomes of children with Congenital Zika Syndrome (CZS) associated microcephaly beyond 2 years of age.MethodWe followed children with CZS-associated microcephaly in an outpatient clinic in Salvador, Brazil. Neurological and neurodevelopmental assessments were performed using the Hammersmith Infant Neurological Examination (HINE) and Bayley Scales of Infant and Toddler Neurodevelopment (Bayley-III) respectively.ResultsOf the 42 children included, 19 were male (45.2%); median (interquartile range) age at neurological evaluation was 28 (25–32) months, and 36 (85.7%) had severe microcephaly. HINE and Bayley-III results were completed for 35/42 (83.3%) and 33/42 (78.5%) children respectively. Bayley-III identified a severe developmental delay in 32/33 (97.0%) children while 1/33 (3.0%) had only a mild delay. In the multivariable analysis, we found that Bayley-III and HINE scores were correlated. Better HINE scores were associated with higher Bayley-III cognitive raw scores (β = 0.29; CI 95% = 0.02–0.57) and motor raw scores (β = 0.43; CI 95% = 0.04–0.82) after adjusting for head circumference, prematurity, and age at neurodevelopmental evaluation. Furthermore, we found that greater head circumference at follow up was associated with higher cognitive (β = 1.27; CI 95% = 0.01–2.53) and motor raw scores (β = 2.03; CI 95% = 0.25–3.81).ConclusionChildren with CZS-associated microcephaly demonstrate severe neurodevelopmental delays and slower growth rates than their peers over time. Still, they have remarkably heterogeneous neurodevelopmental profiles according to neurological exam scores which correlate with their long-term outcomes. We found that HINE scores effectively captured the heterogeneity of neurological capabilities among these children and could be predictive of cognitive and motor development progress.
Highlights
Congenital Zika Virus (ZIKV) infection is associated with severe neurological abnormalities such as microcephaly and central nervous system malformation [1]
Development of children with Congenital Zika Syndrome associated microcephaly century (INTERGROWTH-21st), who were born during the peak of the ZIKV epidemic in Salvador between October 1st, 2015 and January 31th, 2016 at Hospital Geral Roberto Santos (HGRS) or nearby health centers and who received follow-up attention at the HGRS Microcephaly Outpatient Clinic
Widely used tools like the composite scores from the Bayley III exam are effective ways to characterize most children [14], we found that they have difficulties differentiating between children with Congenital Zika syndrome (CZS)-associated microcephaly, due to the severity of developmental delays within this population [5]
Summary
Congenital Zika Virus (ZIKV) infection is associated with severe neurological abnormalities such as microcephaly and central nervous system malformation [1]. Previous studies have found major neurodevelopmental delays of around 20 months in children less than 2 years of age with CZS-associated microcephaly, [4] cases have been identified in which children with CZS-associated microcephaly underwent approximately normal neurodevelopment [5,6,7,8], including one case report which describes a child showing normal neurodevelopment despite CZS-associated microcephaly (head circumference Z-score −2.4 SD) [9] These heterogeneous findings suggest significant variation in developmental outcomes for children exposed to ZIKV in utero. This study aims to characterize the neurodevelopmental outcomes of children with CZS-associated microcephaly between 24–40 months of age
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