Heterogeneous development of children with Congenital Zika Syndrome-associated microcephaly
Juan P. Aguilar Ticona, Nívison Nery, Simon Doss-Gollin, Claudia Gambrah-Lyles, Millani Souza de Almeida Lessa, Valmir N. Rastely-Junior, Adriana Bona Matos, Bruno de Paula Freitas, Ana Borja, Elsio A. Wunder, Verena Ballalai, Carina Vieira, Jaqueline S. Cruz, Daiana de Oliveira, Danielle Bastos Araújo, Danielle Bruna Leal Oliveira, Denicar Lina Nascimento Fabris Maeda, Érica Araújo Mendes, Camila Pereira Soares, Edison Luíz Durigon, Luís Carlos de Souza Ferreira, Rubens Belfort, Antonio R.P. de Almeida, Jamary Oliveira‐Filho, Mitermayer Galvão dos Reis, Albert I. Ko, Federico Costa
Abstract
OBJECTIVE: To describe the neurological and neurodevelopmental outcomes of children with Congenital Zika Syndrome (CZS) associated microcephaly beyond 2 years of age. METHOD: We 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. RESULTS: Of 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). CONCLUSION: Children 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.