Congenital Zika Virus Infection Beyond Neonatal Microcephaly

Congenital Zika Virus Infection Beyond Neonatal Microcephaly

Author de Oliveira Melo, Adriana Suely Google Scholar
Aguiar, Renato Santana Google Scholar
Ramos Amorim, Melania Maria Google Scholar
Arruda, Monica B. Google Scholar
Melo, Fabiana de Oliveira Google Scholar
Clementino Ribeiro, Suelem Tais Google Scholar
Medeiros Batista, Alba Gean Google Scholar
Ferreira, Thales Google Scholar
dos Santos, Mayra Pereira Google Scholar
Sampaio, Virginia Vilar Google Scholar
Martins Moura, Sarah Rogeria Google Scholar
Rabello, Luciana Portela Google Scholar
Gonzaga, Clarissa Emanuelle Google Scholar
Malinger, Gustavo Google Scholar
Ximenes, Renato Google Scholar
Oliveira-Szejnfeld, Patricia Soares de Autor UNIFESP Google Scholar
Tovar-Moll, Fernanda Google Scholar
Chimelli, Leila Google Scholar
Silveira, Paola Paz Google Scholar
Delvechio, Rodrigo Google Scholar
Higa, Luiza Google Scholar
Campanati, Loraine Google Scholar
Nogueira, Rita M. R. Google Scholar
Bispo Filippis, Ana Maria Google Scholar
Szejnfeld, Jacob Autor UNIFESP Google Scholar
Voloch, Carolina Moreira Google Scholar
Ferreira, Orlando C., Jr. Google Scholar
Brindeiro, Rodrigo M. Google Scholar
Tanuri, Amilcar Google Scholar
Abstract IMPORTANCE Recent studies have reported an increase in the number of fetuses and neonates with microcephaly whose mothers were infected with the Zika virus (ZIKV) during pregnancy. To our knowledge, most reports to date have focused on select aspects of the maternal or fetal infection and fetal effects. OBJECTIVE To describe the prenatal evolution and perinatal outcomes of 11 neonates who had developmental abnormalities and neurological damage associated with ZIKV infection in Brazil. DESIGN, SETTING, AND PARTICIPANTS We observed 11 infants with congenital ZIKV infection from gestation to 6 monthus in the state of Paraba, Brazil. Ten of 11 women included in this study presented with symptoms of ZIKV infection during the first half of pregnancy, and all 11 had laboratory evidence of the infection in several tissues by serology or polymerase chain reaction. Brain damage was confirmed through intrauterine ultrasonography and was complemented by magnetic resonance imaging. Histopathological analysis was performed on the placenta and brain tissue from infants who died. The ZIKV genome was investigated in several tissues and sequenced for further phylogenetic analysis. MAIN OUTCOMES AND MEASURES Description of the major lesions caused by ZIKV congenital infection. RESULTS Of the 11 infants, 7 (63.6%) were female, and the median (SD) maternal age at delivery was 25 (6) years. Three of 11 neonates died, giving a perinatal mortality rate of 27.3%. The median (SD) cephalic perimeter at birth was 31 (3) cm, a value lower than the limit to consider a microcephaly case. In all patients, neurological impairments were identified, including microcephaly, a reduction in cerebral volume, ventriculomegaly, cerebellar hypoplasia, lissencephaly with hydrocephalus, and fetal akinesia deformation sequence (ie, arthrogryposis). Results of limited testing for other causes of microcephaly, such as genetic disorders and viral and bacterial infections, were negative, and the ZIKV genome was found in both maternal and neonatal tissues (eg, amniotic fluid, cord blood, placenta, and brain). Phylogenetic analyses showed an intrahost virus variation with some polymorphisms in envelope genes associated with different tissues. CONCLUSIONS AND RELEVANCE Combined findings from clinical, laboratory, imaging, and pathological examinations provided a more complete picture of the severe damage and developmental abnormalities caused by ZIKV infection than has been previously reported. The term congenital Zika syndrome is preferable to refer to these cases, as microcephaly is just one of the clinical signs of this congenital malformation disorder.
xmlui.dri2xhtml.METS-1.0.item-coverage Chicago
Language English
Sponsor Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Prefeitura Municipal de Campina Grande
Date 2016
Published in Jama Neurology. Chicago, v. 73, n. 12, p. 1407-1416, 2016.
ISSN 2168-6149 (Sherpa/Romeo, impact factor)
Publisher Amer Medical Assoc
Extent 1407-1416
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000391122200011

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