Developmental outcomes in children exposed to Zika virus in utero from a Brazilian urban slum cohort study.

BackgroundThe prevalence of developmental alterations associated with in-utero Zika virus (ZIKV) exposure in children is not well understood. Furthermore, estimation of the Population Attributable Fraction (PAF) of developmental alterations attributed to ZIKV has not been performed due to lack of population-based cohorts with data on symptomatic and asymptomatic ZIKV exposures and an appropriate control group. The aim of this study was to characterize neurodevelopmental outcomes of children at 11 to 32 months of age with intrauterine ZIKV exposure and estimate the PAF of alterations secondary to ZIKV exposure.Methodology/principal findingsWe performed a cohort of biannual community-based prospective serosurveys in a slum community in Salvador, Brazil. We recruited women participating in our cohort, with a documented pregnancy from January 2015 to December 2016 and children born to those mothers. Children were classified as ZIKV exposed in utero (born from women with ZIKV seroconversion during pregnancy) or unexposed (born from women without ZIKV seroconversion or that seroconverted before/after pregnancy) by using an IgG monoclonal antibody blockade-of-binding (BoB). We interviewed mothers and performed anthropometric, audiometric, ophthalmological, neurologic, and neurodevelopmental evaluations of their children at 11 to 32 months of age. Among the 655 women participating in the cohort, 66 (10%) were pregnant during the study period. 46 (70%) of them completed follow-up, of whom ZIKV seroconversion occurred before, during, and after pregnancy in 25 (54%), 13 (28%), and 1 (2%), respectively. The rest of women, 7 (21.2%), did not present ZIKV seroconversion. At 11 to 32 months of life, the 13 ZIKV-exposed children had increased risk of mild cognitive delay (RR 5.1; 95%CI 1.1-24.4) compared with the 33 children unexposed, with a PAF of 53.5%. Exposed children also had increased risk of altered auditory behavior (RR 6.0; 95%CI 1.3-26.9), with a PAF of 59.5%.ConclusionsA significant proportion of children exposed in utero to ZIKV developed mild cognitive delay and auditory behavioral abnormalities even in the absence of gross birth defects such as microcephaly and other neurodevelopmental domains. Furthermore, our findings suggest that over half of these abnormalities could be attributed to intrauterine ZIKV exposure

Unequal burden of Zika-associated microcephaly among populations with public and private healthcare in Salvador, Brazil

This study was supported by Oswaldo Cruz Foundation; Secretariat of Health Surveillance; Brazilian Ministry of Health; Wellcome Trust, Grant/Award Number: 102330/Z/13/Z; NSF-NIH, Grant/Award Number: 5 R01 AI052473, 5 U01 AI088752, 1 R25 TW009338, 1 R01 AI121207, F31 AI114245, R01 AI052473, U01 AI088752, R01 TW009504, and R25 TW009338. Fogarty International Center (R25 TW009338). Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) projects 2016/08727-5 and National Council for Scientific and Technological Development – CNPq. Fundação de Amparo à Pesquisa do Estado da Bahia (FAPESB) projeto (PET0021/2016)Yale School of Public Health. New Haven, USAHospital Aliança. Salvador, BA, BrazilYale School of Public Health. New Haven, USAFundação Oswaldo Cruz. Salvador, BA, BrazilSecretária da Saúde do Estado da Bahia. Hospital Geral Roberto Santos. Salvador, BA, BrazilUniversidade Federal da Bahia. Instituto da Saúde Coletiva. Hospital Universitário Professor Edgard Santos. Faculdade de Medicina da Bahia. Salvador, BA, BrazilSecretária da Saúde do Estado da Bahia. Hospital Geral Roberto Santos. Salvador, BA, BrazilSecretária da Saúde do Estado da Bahia. Hospital Geral Roberto Santos. Salvador, BA, BrazilSecretária da Saúde do Estado da Bahia. Hospital Geral Roberto Santos. Salvador, BA, BrazilSecretária da Saúde do Estado da Bahia. Hospital Geral Roberto Santos. Salvador, BA, BrazilUniversidade Federal da Bahia. Instituto da Saúde Coletiva. Hospital Universitário Professor Edgard Santos. Faculdade de Medicina da Bahia. Salvador, BA, BrazilFundação Oswaldo Cruz. Salvador, BA, BrazilSecretária da Saúde do Estado da Bahia. Hospital Geral Roberto Santos. Salvador, BA, BrazilUniversidade Federal da Bahia. Faculdade de Medicina. Programa de Pós-graduação em Ciências da Saude. Salvador, BA, BrazilFundação Oswaldo Cruz. Salvador, BA, BrazilMinistério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, BrasilMinistério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, BrasilMinistério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, BrasilUniversidade Federal da Bahia. Instituto da Saúde Coletiva. Hospital Universitário Professor Edgard Santos. Faculdade de Medicina da Bahia. Salvador BA, BrazilFundação Oswaldo Cruz. Salvador, BA, BrazilFundação Oswaldo Cruz. Salvador, BA, BrazilSecretária da Saúde do Estado da Bahia. Hospital Geral Roberto Santos. Salvador, BA, Brazil / King’s College Hospital. Harris Birthright Center for Fetal Medicine. London, UK / Universidade Federal da Bahia. Instituto da Saúde Coletiva. Hospital Universitário Professor Edgard Santos. Faculdade de Medicina da Bahia. Salvador, BA, BrazilSecretária da Saúde do Estado da Bahia. Hospital Geral Roberto Santos. Salvador, BA, Brazil / Escola Paulista de Medicina. São Paulo, SP, BrazilSecretária da Saúde do Estado da Bahia. Hospital Geral Roberto Santos. Salvador, BA, BrazilFundação Oswaldo Cruz. Salvador, BA, BrazilYale School of Public Health. New Haven, USA / Fundação Oswaldo Cruz. Salvador, BA, Brazil / Universidade Federal da Bahia. Instituto da Saúde Coletiva. Hospital Universitário Professor Edgard Santos. Faculdade de Medicina da Bahia. Salvador, BA, BrazilYale School of Public Health. New Haven, USAYale School of Public Health. New Haven, USA / Universidade Federal da Bahia. Salvador, BA, BrazilObjectives: To describe the differences in clinical presentation and relative disease burden of congenital Zika syndrome (CZS)-associated microcephaly at 2 large hospitals in Salvador, Brazil that serve patients of different socioeconomic status (SES). Methods: Clinical and serologic data were collected prospectively from pregnant women and their infants, who delivered at 2 study centers during the 2015–2016 Zika virus (ZIKV) epidemic in Salvador, Brazil. Results: Pregnant women from Salvador, Brazil delivering in a low SES hospital had 3 times higher ZIKV exposure rate than women at a high SES hospital. However, different SES hospitals had similar prevalence of infants with CZS-associated microcephaly (10% vs 6%, p = 0.16) after controlling for ZIKV exposure in their mothers. Conclusions: Our study supports the positive association between low SES, high maternal ZIKV exposure, and high rates of CZS-associated microcephaly