Three-Year Clinical Follow-Up of Children Intrauterine Exposed to Zika Virus

Congenital Zika virus (ZIKV) infection may present with a broad spectrum of clinical manifestations. Some sequelae, particularly neurodevelopmental problems, may have a later onset. We conducted a prospective cohort study of 799 high-risk pregnant women who were followed up until delivery. Eighty-three women and/or newborns were considered ZIKV exposed and/or infected. Laboratory diagnosis was made by polymerase chain reaction in the pregnant mothers and their respective newborns, as well as Dengue virus, Chikungunya virus, and ZIKV serology. Serology for toxoplasmosis, rubella, cytomegalovirus, herpes simplex virus, and syphilis infections were also performed in microcephalic newborns. The newborns included in the study were followed up until their third birthday. Developmental delay was observed in nine patients (13.2%): mild cognitive delay in three patients, speech delay in three patients, autism spectrum disorder in two patients, and severe neurological abnormalities in one microcephalic patient; sensorineural hearing loss, three patients and dysphagia, six patients. Microcephaly due to ZIKV occurred in three patients (3.6%). Clinical manifestations can appear after the first year of life in children infected/exposed to ZIKV, emphasizing the need for long-term follow-up

Prevalence and diagnostic accuracy of microcephaly in a pediatric cohort in Brazil: a retrospective cross-sectional study

Anormalitats congènites; Epidemiologia; MicrocefàliaAnomalías congénitas; Epidemiología; MicrocefaliaCongenital abnormalities; Epidemiology; MicrocephalyObjective We sought to describe the prevalence of microcephaly and to compare the different cutoff points established by the Brazilian Ministry of Health at various times during a Zika virus epidemic. As a secondary aim, we investigated the possible etiology of the microcephaly. Method This retrospective study utilized newborn participants in the Zika Cohort Study Jundiaí. Newborns from the Zika Cohort Study Jundiaí with an accurate gestational age determination and complete anthropometric data were analyzed, and microcephaly was diagnosed according to the INTERGROWTH-21st curve. At delivery, fluids were tested for specific antibodies and for viruses. Brain images were evaluated for microcephaly. Receiver Operating Characteristic curves were plotted to define the accuracy of different cutoff points for microcephaly diagnosis. Results Of 462 eligible newborns, 19 (4.1%) were positive for microcephaly. Cutoff points corresponding to the curves of the World Health Organization yielded the best sensitivity and specificity. Three of the microcephaly cases (15.8%) were positive for Zika virus infections; nine (47.4%) had intrauterine growth restriction; one had intrauterine growth restriction and was exposed to Zika virus; three had a genetic syndrome (15.8%); and three had causes that had not been determined (15.8%). Conclusions Microcephaly prevalence was 4.1% in this study. Cutoff values determined by the World Health Organization had the highest sensitivity and specificity in relation to the standard IG curve. The main reason for microcephaly was intrauterine growth restriction. All possible causes of microcephaly must be investigated to allow the best development of an affected baby.This work and this manuscript were supported by the Fundação de Amparo à Pesquisa do Estado de São Paulo (SDP#grant 2016/08578-0), the Brazilian Ministry of Health (SDP#grant 861306/2017 and 861307/2017), and the London School of Hygiene and Tropical Medicine (SDP#grant PC0002/16)

Risk of adverse outcomes in offspring with RT-PCR confirmed prenatal Zika virus exposure: an individual participant data meta-analysis of 13 cohorts in the Zika Brazilian Cohorts ConsortiumResearch in context

Summary: Background: Knowledge regarding the risks associated with Zika virus (ZIKV) infections in pregnancy has relied on individual studies with relatively small sample sizes and variable risk estimates of adverse outcomes, or on surveillance or routinely collected data. Using data from the Zika Brazilian Cohorts Consortium, this study aims, to estimate the risk of adverse outcomes among offspring of women with RT-PCR-confirmed ZIKV infection during pregnancy and to explore heterogeneity between studies. Methods: We performed an individual participant data meta-analysis of the offspring of 1548 pregnant women from 13 studies, using one and two-stage meta-analyses to estimate the absolute risks. Findings: Of the 1548 ZIKV-exposed pregnancies, the risk of miscarriage was 0.9%, while the risk of stillbirth was 0.3%. Among the pregnancies with liveborn children, the risk of prematurity was 10,5%, the risk of low birth weight was 7.7, and the risk of small for gestational age (SGA) was 16.2%. For other abnormalities, the absolute risks were: 2.6% for microcephaly at birth or first evaluation, 4.0% for microcephaly at any time during follow-up, 7.9% for neuroimaging abnormalities, 18.7% for functional neurological abnormalities, 4.0% for ophthalmic abnormalities, 6.4% for auditory abnormalities, 0.6% for arthrogryposis, and 1.5% for dysphagia. This risk was similar in all sites studied and in different socioeconomic conditions, indicating that there are not likely to be other factors modifying this association. Interpretation: This study based on prospectively collected data generates the most robust evidence to date on the risks of congenital ZIKV infections over the early life course. Overall, approximately one-third of liveborn children with prenatal ZIKV exposure presented with at least one abnormality compatible with congenital infection, while the risk to present with at least two abnormalities in combination was less than 1.0%. Funding: National Council for Scientific and Technological Development - Brazil (Conselho Nacional de Desenvolvimento Científico e Tecnológico – CNPq); Wellcome Trust and the United Kingdom's Department for International Development; European Union's Horizon 2020 research and innovation program; Medical Research Council on behalf of the Newton Fund and Wellcome Trust; National Institutes of Health/National Institute of Allergy and Infectious Diseases; Foundation Christophe et Rodolphe Mérieux; Coordination for the improvement of Higher Education Personnel (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Capes); Ministry of Health of Brazil; Brazilian Department of Science and Technology; Foundation of Research Support of the State of São Paulo (Fundação de Amparo à Pesquisa do Estado de São Paulo – FAPESP); Foundation of Research Support of the State of Rio de Janeiro (Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro – FAPERJ); Foundation of Support for Research and Scientific and Technological Development of Maranhão; Evandro Chagas Institute/Brazilian Ministry of Health (Instituto Evandro Chagas/Ministério da Saúde); Foundation of Research Support of the State of Goiás (Fundação de Amparo à Pesquisa do Estado de Goiás – FAPEG); Foundation of Research Support of the State of Rio Grande do Sul (Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul – FAPERGS); Foundation to Support Teaching, Research and Assistance at Hospital das Clínicas, Faculty of Medicine of Ribeirão Preto (Fundação de Apoio ao Ensino, Pesquisa e Assistência do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto); São Paulo State Department of Health (Secretaria de Saúde do Estado de São Paulo); Support Foundation of Pernambuco Science and Technology (Fundação de Amparo à Ciência e Tecnologia de Pernambuco – FACEPE)