Delayed childhood neurodevelopment and neurosensory alterations in the second year of life in a prospective cohort of ZIKV-exposed children

Abstract

We report neurodevelopmental outcomes in 216 infants followed since the time of PCR-confirmed maternal Zika virus (ZIKV) infection in pregnancy during the Rio de Janeiro epidemic of 2015–2016 (refs. 1,2). Neurodevelopment was assessed by Bayley Scales of Infant and Toddler Development, third edition (Bayley-III; cognitive, language and motor domains) in 146 children and through neurodevelopment questionnaires/neurological examinations in 70 remaining children. Complete eye exams (n = 137) and hearing assessments (n = 114) were also performed. Below-average neurodevelopment and/or abnormal eye or hearing assessments were noted in 31.5% of children between 7 and 32 months of age. Among children assessed by Bayley-III, 12% scored below –2 s.d. (score <70; a score of 100 ± 2 s.d. is the range) in at least one domain; and 28% scored between −1 and −2 s.d. in any domain (scores <85–70). Language function was most affected, with 35% of 146 children below average. Improved neurodevelopmental outcomes were noted in female children, term babies, children with normal eye exams and maternal infection later in pregnancy (P = 0.01). We noted resolution of microcephaly with normal neurodevelopment in two of eight children, development of secondary microcephaly in two other children and autism spectrum disorder in three previously healthy children in the second year of life.

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Fig. 1
Fig. 2: Bayley-III assessments in 146 children between the ages of 7 and 32 months.
Fig. 3: Gestational age at time of maternal Zika virus infection in 244 pregnancies.

Data availability

The data sets generated during and/or analysed during the current study are available from the corresponding author upon reasonable request.

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Acknowledgements

This study was supported by the Departamento de Ciência e Tecnologia do Ministério da Saúde do Brasil (DECIT/25000.072811/2016-19, to P.B. and M.E.M.); Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES 001/88887.116627/2016-01 to PB); Brazilian National Council for Scientific and Technological Development (CNPq/441098/2016-9 to M.E.M. and CNPq307282/2017-1 to P.B.); Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ, No. E-18/2015TXB to M.E.M., No. 239224/E-032018 to M.E.M. and No. E-26/202.862/2018 to P.B.); Fondation Christophe e Rodolphe Mérieux to P.B.; ZikAlliance, 734548 to P.B.; the Thrasher Research Fund (No. 20164370 to K.N.S. and K.A.); the Bill and Melinda gates Foundation Grand Challenges Explorations (No. OPP112887 to P.B.M.); the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (No. AI28697 to K.N.S., No. AI1259534-01 to K.N.S. and G.C., No. AI140718-01 to K.N.S. and P.B.); the National Eye Institute (NEI) of the National Institutes of Health (No. AI129847-01 to K.N.S., I.T. and P.B.); the United Kingdom’s Department for International Development (to M.E.M.); and the ZikaPlan (Preparedness Latin American Network, to M.E.M.). We thank the women who enrolled in this study, the Fiocruz Zika Field Team who rendered our work possible, and P.F. Augusto and C.B. de Souza (Federal University of São Paulo), who assisted with neurodevelopmental assessments.

Author information

K.N.-S., P.B., C.R.G., J.P.P. and M.E.M. conceived and designed the study. K.N.-S., P.B, T.K., Z.V., L.D., M.P., L.M.A.d.C., S.M.P., A.A.Z., I.T., T.R.S.S., D.C.d.C., R.P.C., J.M., A.B.R., R.H.H., C.Y.P.A., F.F.G., J.P.P., S.L.G. and M.E.M. were responsible for data collection and accuracy checking of data. K.N.-S., P.B, T.K. and Z.V. were responsible for data analysis. K.N.-S., P.B, T.K., Z.V., K.A., C.R.G., L.D., A.A.Z., I.T., C.E., P.B.M., J.D.C., Z.X., G.C. and M.E.M. were responsible for interpreting the data. K.N.-S., P.B, Z.V., T.K. and M.E.M. drafted the manuscript. All authors critically revised the manuscript and gave final approval of the version to be published.

Correspondence to Karin Nielsen-Saines or Maria Elisabeth Moreira.

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