Zika-related adverse outcomes in a cohort of pregnant women with rash in Pernambuco, Brazil.

Ricardo Arraes De Alencar Ximenes,Luciana Caroline Albuquerque Bezerra,Celina Maria Turchi Martelli,Adriana L Gois,Regina Coeli Ferreira Ramos,Maria De Fátima Pessoa Militão De Albuquerque Albuquerque,Laura C Rodrigues,Sinval Pinto Brandão-Filho,Sandra Valongueiro,Liana O Ventura,Sophie Helena Eickmann,Pedro Pires,Camila V Ventura,Demócrito De Barros Miranda-Filho,George Santiago Dimech ,Ulísses Ramos Montarroyos ,Marli Tenório Cordeiro ,Ernesto Torres Azevedo Marques-Júnior ,Mariana De Carvalho Leal ,Wayner Vieira De Souza ,Maria Durce Costa Gomes Carvalho ,Thália Velho Barreto De Araújo ,Maria Ângela Wanderley Rocha ,Danilo Oliveira ,Priscila M S Castanha ,Paula F S Da Silva ,Rafael Dhália ,Elizabeth B Brickley

doi:10.1371/journal.pntd.0009216

Abstract

BackgroundWhile Zika virus (ZIKV) is now widely recognized as a teratogen, the frequency and full spectrum of adverse outcomes of congenital ZIKV infection remains incompletely understood.MethodsParticipants in the MERG cohort of pregnant women with rash, recruited from the surveillance system from December/2015-June/2017. Exposure definition was based on a combination of longitudinal data from molecular, serologic (IgM and IgG3) and plaque reduction neutralization tests for ZIKV. Children were evaluated by a team of clinical specialists and by transfontanelle ultrasound and were classified as having microcephaly and/or other signs/symptoms consistent with congenital Zika syndrome (CZS). Risks of adverse outcomes were quantified according to the relative evidence of a ZIKV infection in pregnancy.Findings376 women had confirmed and suspected exposure to ZIKV. Among evaluable children born to these mothers, 20% presented with an adverse outcome compatible with exposure to ZIKV during pregnancy. The absolute risk of microcephaly was 2.9% (11/376), of calcifications and/or ventriculomegaly was 7.2% (13/180), of additional neurologic alterations was 5.3% (13/245), of ophthalmologic abnormalities was 7% (15/214), and of dysphagia was 1.8% (4/226). Less than 1% of the children experienced abnormalities across all of the domains simultaneously. Interpretation: Although approximately one-fifth of children with confirmed and suspected exposure to ZIKV in pregnancy presented with at least one abnormality compatible with CZS, the manifestations presented more frequently in isolation than in combination. Due to the rare nature of some outcomes and the possibility of later manifestations, large scale individual participant data meta-analysis and the long-term evaluation of children are imperative to identify the full spectrum of this syndrome and to plan actions to reduce damages.

Highlights

Since the start of the microcephaly epidemic in the Americas in 2015, evidence detailing the consequences of prenatal exposure to Zika virus (ZIKV) has been accumulating
As methodological issues limit the comparability of the existing findings, the spectrum of abnormalities arising from prenatal exposure to ZIKV and the risk of each of them—either separately or in combination —remains incompletely understood
We considered there to be evidence against ZIKV infection if all tests performed in pregnancy were negative

Summary

Introduction

Since the start of the microcephaly epidemic in the Americas in 2015, evidence detailing the consequences of prenatal exposure to Zika virus (ZIKV) has been accumulating. There is wide variation in the estimated frequencies of other adverse outcomes, ranging from 6 [7] to 46% [6]. These other outcomes mainly include grossly abnormal clinical or brain imaging findings or both [6], often accompanied by neurologic and ocular defects [7]. As methodological issues limit the comparability of the existing findings, the spectrum of abnormalities arising from prenatal exposure to ZIKV and the risk of each of them—either separately or in combination —remains incompletely understood. While Zika virus (ZIKV) is widely recognized as a teratogen, the frequency and full spectrum of adverse outcomes of congenital ZIKV infection remains incompletely understood

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Discussion

Conclusion