Would Zika virus Infection in Pregnancy Be a Sentence of Poor Neurological Prognosis for Exposed Children? Neurodevelopmental Outcomes in a Cohort from Brazilian Amazon

Infections with Flavivirus in pregnant women are not associated with vertical transmission. However, in 2015, severe cases of congenital infection were reported during the Zika virus outbreak in Brazil. More subtle infections in children born to mothers with ZIKV still remain uncertain and the spectrum of this new congenital syndrome is still under construction. This study describes outcomes regarding neurodevelopment and neurological examination in the first years of life, of a cohort of 77 children born to pregnant women with ZIKV infection in Manaus, Brazil, from 2017 to 2020. In the group of normocephalic children (92.2%), most showed satisfactory performance in neuropsychomotor development, with a delay in 29.6% and changes in neurological examination in 27.1%, with two children showing muscle-strength deficits. All microcephalic children (5.2%) evolved with severe neuropsychomotor-development delay, spastic tetraparesis, and alterations in the imaging exam. In this cohort, 10.5% of the children had macrocephaly at birth, but only 2.6% remained in this classification. Although microcephaly has been considered as the main marker of congenital-Zika-virus syndrome in previous studies, its absence does not exclude the possibility of the syndrome. This highlights the importance of clinical follow-up, regardless of the classification of head circumference at birth

Epilepsy as a sign of brain tumor in the childhood and adolescence: features and outcome

A epilepsia associada a tumor cerebral é uma condição debilitante, causadora de importante prejuízo sobre a qualidade de vida dos que sofrem desta condição. Relacionada à grande refratariedade ao tratamento medicamentoso, tanto a epilepsia quanto o uso de drogas antiepilépticas (DAEs) predispõem à deterioração das funções cognitivas. Em casos raros, a epilepsia secundária a tumor cerebral pode ser devastadora, aumentando os riscos de morte súbita. Buscando auxiliar a tomada de decisões e enfatizando os benefícios de uma discussão ampla entre equipes de oncologia, neurologia infantil, epilepsia e neurocirurgia, este trabalho objetiva descrever as características clínicas gerais, eletroencefalográficas, histopatológicas dos pacientes, verificar o impacto do tratamento cirúrgico sobre a epilepsia quanto ao desfecho clínico relacionado ao controle das crises, comparar os resultados da avaliação cognitiva nos períodos pré e pós-operatórios e descrever a ocorrência de complicações cirúrgicas intra-operatórias, pós-operatórias e óbitos. Trata-se de estudo observacional transversal retrospectivo, por revisão de prontuários de pacientes com idade inferior a 19 anos quando submetidos à cirurgia para tratamento de epilepsia refratária secundária a tumores cerebrais entre 1996 e 2013, pela equipe do Centro de Cirurgia de Epilepsia do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto. Para análise dos desfechos quanto à incidência de crises, utilizou-se a classificação de Engel, adaptada para uso após o primeiro ano da cirurgia. Procedeu-se à análise descritiva dos dados. Foram incluídas 27 crianças, com média de 6,0 anos (3 meses a 15,8 anos) no início dos sintomas. O intervalo entre o início das crises epilépticas e o diagnóstico do tumor foi de 3,6 anos (um mês a 14,5 anos). A média da quantidade de drogas antiepilépticas (DAEs) utilizadas antes da cirurgia foi 3,6. A média da idade no diagnóstico do tumor cerebral foi 9,7 anos (10 meses a 16,8 anos). A localização do tumor foi lobo temporal em 59,2%, sendo ganglioglioma e DNET os mais frequentes, em igual proporção, 33,3%. Envolvimento de área eloquente ocorreu em 18,5%. A vídeomonitorização eletrográfica evidenciou descargas focais na área tumoral em 85,2%. O intervalo entre o diagnóstico tumoral e a realização da cirurgia foi de 1,5 anos (dias a 7 anos). A média de idade dos pacientes no momento da cirurgia foi 11,3 anos (3 a 17, 4 anos). A ressecção tumoral foi completa em 88,8% dos pacientes. Complicação pós-cirúrgica, osteomielite, ocorreu em 1 (3,7%). Um paciente (3,7%) com oligodendroglioma anaplásico foi a óbito após 2 anos da cirurgia. Os desfechos clínicos relacionados ao controle de crises dos pacientes submetidos à cirurgia foram satisfatórios, com Engel I correspondendo a 92,6% no primeiro ano pós-operatório. Apenas 14,8% apresentaram Engel III - IV durante todo o período de seguimento. A média do tempo para retirada das DAEs após a cirurgia foi de 3,2 anos (1,7 a 7 anos). Alterações neurológicas após a cirurgia ocorreram em 18,5%, sendo os déficits neurológicos focais transitórios. Evoluíram com melhora do perfil intelectual 31,3%, inalterado 50% e piora 18,7%. A cirurgia para tratamento da epilepsia secundária a tumor cerebral evidenciou-se uma modalidade terapêutica potencialmente curativa e segura, portanto, o diagnóstico tumoral não pode ser postergadoTumor-associated epilepsy is a debilitating condition causing injury to the quality of life of those who suffer from a brain tumor. It has been shown to have a greater refractivity to antiepileptic drug therapy. Both epilepsy and the use of antiepileptic drugs have a predisposition to the deterioration of cognitive functions. In rare cases tumor-associated epilepsy can be devastating, increasing the risk of sudden death. Seeking help with decisionmaking and emphasizing the benefits of a broad discussion among oncology teams, child neurology, epilepsy and neurosurgery, this paper describes the general, clinical, electroencephalographic, and histopathological patient characteristics, verifies the impact of surgical treatment of epilepsy as the clinical outcome related to the control of seizures, compares the result of cognitive assessment in the pre to the postoperative and describes the occurrence of intraoperative surgical complications and postoperative deaths. It is a retrospective cross-sectional observational study, by review of medical records of patients under the age of 19 who underwent surgery to treat tumor-associated epilepsy between 1996 and 2013, by the Epilepsy Surgery Center of the Hospital of School of Medicine of Ribeirão Preto, São Paulo University. For analysis of outcomes in the incidence of crises, the Engel classification was used and adapted for use after the first year of surgery. It was used with the descriptive analysis of the data. Twenty seven children were included, with a mean of 6.0 years (3 months to 15.8 years) at the beginning of symptoms. The interval between the onset of seizures and the diagnosis of the tumor was 3.6 years (1 month to 14.5 years). The average number of antiepileptic drugs (AEDs) used before surgery was 3.6. The average age at diagnosis of brain tumor was 9.7 years (10 months to 16.8 years). The tumor site was the temporal lobe in 59.2% of patients and ganglioglioma and DNET were the most common, in equal proportion, 33.3%. Eloquent area of involvement occurred in 18.5%. The electrographic video monitoring showed focal discharges at the tumor site in 85.2% of patients. The interval between tumor diagnosis and the surgery was 1.5 years (days to 7 years). The average patient age at surgery was 11.3 years (3-17, 4 years). Tumor resection was complete in 88.8% of patients. Post-surgical complication, osteomyelitis, occurred in 1 (3.7%) of patients. Only one patient (3,7%) had anaplastic oligodendroglioma and dead two years after surgery. Clinical outcomes related to the control of seizures in patients undergoing surgery were satisfactory, with Engel I corresponding to 92,6% in the first year of follow up. Only 14.8% had Engel III - IV during the follow-up period. The average time for withdrawal of AEDs after surgery was 3.2 years (1.7 to 7 years). Neurological changes after surgery occurred in 18.5%, and were transient focal neurological deficits. The improvement of the intellectual profile occurred in 31.3%, unchanged in 50% and 18.7% worsened. Surgery to treat tumor-associated epilepsy showed up a potentially curative and safe therapeutic modality, therefore, tumor diagnosis cannot be postpone

Epilepsy as a sign of brain tumor in the childhood and adolescence: features and outcome

A epilepsia associada a tumor cerebral é uma condição debilitante, causadora de importante prejuízo sobre a qualidade de vida dos que sofrem desta condição. Relacionada à grande refratariedade ao tratamento medicamentoso, tanto a epilepsia quanto o uso de drogas antiepilépticas (DAEs) predispõem à deterioração das funções cognitivas. Em casos raros, a epilepsia secundária a tumor cerebral pode ser devastadora, aumentando os riscos de morte súbita. Buscando auxiliar a tomada de decisões e enfatizando os benefícios de uma discussão ampla entre equipes de oncologia, neurologia infantil, epilepsia e neurocirurgia, este trabalho objetiva descrever as características clínicas gerais, eletroencefalográficas, histopatológicas dos pacientes, verificar o impacto do tratamento cirúrgico sobre a epilepsia quanto ao desfecho clínico relacionado ao controle das crises, comparar os resultados da avaliação cognitiva nos períodos pré e pós-operatórios e descrever a ocorrência de complicações cirúrgicas intra-operatórias, pós-operatórias e óbitos. Trata-se de estudo observacional transversal retrospectivo, por revisão de prontuários de pacientes com idade inferior a 19 anos quando submetidos à cirurgia para tratamento de epilepsia refratária secundária a tumores cerebrais entre 1996 e 2013, pela equipe do Centro de Cirurgia de Epilepsia do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto. Para análise dos desfechos quanto à incidência de crises, utilizou-se a classificação de Engel, adaptada para uso após o primeiro ano da cirurgia. Procedeu-se à análise descritiva dos dados. Foram incluídas 27 crianças, com média de 6,0 anos (3 meses a 15,8 anos) no início dos sintomas. O intervalo entre o início das crises epilépticas e o diagnóstico do tumor foi de 3,6 anos (um mês a 14,5 anos). A média da quantidade de drogas antiepilépticas (DAEs) utilizadas antes da cirurgia foi 3,6. A média da idade no diagnóstico do tumor cerebral foi 9,7 anos (10 meses a 16,8 anos). A localização do tumor foi lobo temporal em 59,2%, sendo ganglioglioma e DNET os mais frequentes, em igual proporção, 33,3%. Envolvimento de área eloquente ocorreu em 18,5%. A vídeomonitorização eletrográfica evidenciou descargas focais na área tumoral em 85,2%. O intervalo entre o diagnóstico tumoral e a realização da cirurgia foi de 1,5 anos (dias a 7 anos). A média de idade dos pacientes no momento da cirurgia foi 11,3 anos (3 a 17, 4 anos). A ressecção tumoral foi completa em 88,8% dos pacientes. Complicação pós-cirúrgica, osteomielite, ocorreu em 1 (3,7%). Um paciente (3,7%) com oligodendroglioma anaplásico foi a óbito após 2 anos da cirurgia. Os desfechos clínicos relacionados ao controle de crises dos pacientes submetidos à cirurgia foram satisfatórios, com Engel I correspondendo a 92,6% no primeiro ano pós-operatório. Apenas 14,8% apresentaram Engel III - IV durante todo o período de seguimento. A média do tempo para retirada das DAEs após a cirurgia foi de 3,2 anos (1,7 a 7 anos). Alterações neurológicas após a cirurgia ocorreram em 18,5%, sendo os déficits neurológicos focais transitórios. Evoluíram com melhora do perfil intelectual 31,3%, inalterado 50% e piora 18,7%. A cirurgia para tratamento da epilepsia secundária a tumor cerebral evidenciou-se uma modalidade terapêutica potencialmente curativa e segura, portanto, o diagnóstico tumoral não pode ser postergadoTumor-associated epilepsy is a debilitating condition causing injury to the quality of life of those who suffer from a brain tumor. It has been shown to have a greater refractivity to antiepileptic drug therapy. Both epilepsy and the use of antiepileptic drugs have a predisposition to the deterioration of cognitive functions. In rare cases tumor-associated epilepsy can be devastating, increasing the risk of sudden death. Seeking help with decisionmaking and emphasizing the benefits of a broad discussion among oncology teams, child neurology, epilepsy and neurosurgery, this paper describes the general, clinical, electroencephalographic, and histopathological patient characteristics, verifies the impact of surgical treatment of epilepsy as the clinical outcome related to the control of seizures, compares the result of cognitive assessment in the pre to the postoperative and describes the occurrence of intraoperative surgical complications and postoperative deaths. It is a retrospective cross-sectional observational study, by review of medical records of patients under the age of 19 who underwent surgery to treat tumor-associated epilepsy between 1996 and 2013, by the Epilepsy Surgery Center of the Hospital of School of Medicine of Ribeirão Preto, São Paulo University. For analysis of outcomes in the incidence of crises, the Engel classification was used and adapted for use after the first year of surgery. It was used with the descriptive analysis of the data. Twenty seven children were included, with a mean of 6.0 years (3 months to 15.8 years) at the beginning of symptoms. The interval between the onset of seizures and the diagnosis of the tumor was 3.6 years (1 month to 14.5 years). The average number of antiepileptic drugs (AEDs) used before surgery was 3.6. The average age at diagnosis of brain tumor was 9.7 years (10 months to 16.8 years). The tumor site was the temporal lobe in 59.2% of patients and ganglioglioma and DNET were the most common, in equal proportion, 33.3%. Eloquent area of involvement occurred in 18.5%. The electrographic video monitoring showed focal discharges at the tumor site in 85.2% of patients. The interval between tumor diagnosis and the surgery was 1.5 years (days to 7 years). The average patient age at surgery was 11.3 years (3-17, 4 years). Tumor resection was complete in 88.8% of patients. Post-surgical complication, osteomyelitis, occurred in 1 (3.7%) of patients. Only one patient (3,7%) had anaplastic oligodendroglioma and dead two years after surgery. Clinical outcomes related to the control of seizures in patients undergoing surgery were satisfactory, with Engel I corresponding to 92,6% in the first year of follow up. Only 14.8% had Engel III - IV during the follow-up period. The average time for withdrawal of AEDs after surgery was 3.2 years (1.7 to 7 years). Neurological changes after surgery occurred in 18.5%, and were transient focal neurological deficits. The improvement of the intellectual profile occurred in 31.3%, unchanged in 50% and 18.7% worsened. Surgery to treat tumor-associated epilepsy showed up a potentially curative and safe therapeutic modality, therefore, tumor diagnosis cannot be postpone

Refractory epilepsy in children with brain tumors. The urgency of neurosurgery

ABSTRACT In order to verify indications for surgery, 27 patients with refractory epileptic seizures and brain tumor, aged up to 19 years at the time of surgery, were studied between 1996 and 2013 and followed up for at least one year. The mean interval between the onset of seizures and the diagnosis of the tumor was 3.6 years, and from diagnosis to the surgery, 18 months. The location of the tumor was in the temporal lobe in 16, with ganglioglioma and dysembryoplastic neuroepithelial tumors being the most frequent. Among the patients, 92.5% and 90.4% were seizure-free in the first and fifth year after surgery, respectively. Twelve of 16 children were successful in becoming drug-free, with complete withdrawal by 3.2 years. Surgery proved to be potentially curative and safe in these cases, suggesting that the tumor diagnosis and surgery cannot be postponed

Neurological Findings in Children without Congenital Microcephaly Exposed to Zika Virus in Utero: A Case Series Study

The Zika virus can induce a disruptive sequence in the fetal brain and is manifested mainly by microcephaly. Knowledge gaps still exist as to whether the virus can cause minor disorders that are perceived later on during the first years of life in children who are exposed but are asymptomatic at birth. In this case series, we describe the outcomes related to neurodevelopment through the neurological assessment of 26 non-microcephalic children who had intrauterine exposure to Zika virus. Children were submitted for neurological examinations and Bayley Scales-III (cognition, language, and motor performance). The majority (65.4%) obtained satisfactory performance in neurodevelopment. The most impaired domain was language, with 30.7% impairment. Severe neurological disorders occurred in five children (19.2%) and these were spastic hemiparesis, epilepsy associated with congenital macrocephaly (Zika and human immunodeficiency virus), two cases of autism (one exposed to Zika and Toxoplasma gondii) and progressive sensorineural hearing loss (GJB2 mutation). We concluded that non-microcephalic children with intrauterine exposure to Zika virus, in their majority, had achieved satisfactory performance in all neurodevelopmental domains. One third of the cases had some impairment, but the predominant group had mild alterations, with low occurrence of moderate to severe disorders, similar to other studies in Brazil

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

The Zika Brazilian Cohorts Consortium was supported by the National Council for Scientific and Technological Development (Conselho Nacional de Desenvolvimento Científico e Tecnológico – CNPq) (grant number 404861/2018-0). The individual studies participating in the ZBC-Consortium were funded by: Wellcome Trust and the United Kingdom’s Department for International Development (grant numbers: 205377/Z/16/Z; 201870/Z/16/Z). European Union’s Horizon 2020 research and innovation programme under ZikaPLAN (grant number 734584). Wellcome Trust - Research Enrichment in Epidemic Situation (grant number 107779/Z/15/Z; with ER1505 & ER1601). Medical Research Council on behalf of the Newton Fund and Wellcome Trust (grant number MC_PC_15088). National Institutes of Health/National Institute of Allergy and Infectious Diseases (grant number RO1/ AI140718). Fondation Christophe et Rodolphe Mérieux. National Council for Scientific and Technological Development (Conselho Nacional de Desenvolvimento Científico e Tecnológico – CNPq) (grant numbers 443875/2018-9; 440573/2016-5; 441098/2016-9; 305090/2016-0; 307282/2017-1; 304476/2018-8; 465549/2014-4; 440763/2016-9; 309722/2017-9; 306708/2014-0; 440577/2016-0). Coordination for the improvement of Higher Education Personnel (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Capes) (grant numbers 88881.130813/2016-01; 88887.116627/2016-01; 88887.136366/2017-00). Ministry of Health of Brazil - Emergency Response in Public Health - Zika virus and Microcephaly (Ministério da Saúde de Brasil - Resposta à Emergência em Saúde Pública – Zika vírus e Microcefalia) (grant number 837058/2016). Department of Science and Technology (Departamento de Ciência e Tecnologia - DECIT) (grant numbers 25000.072811/2016-19; 440839/2016-5). Foundation of Research Support of the State of São Paulo (Fundação de Amparo à Pesquisa do Estado de São Paulo – FAPESP) (grant numbers 2016/08578-0; 2017/21688-1; 2013/21719-3; 2016/ 15021-1; 2015/12295-0; 2016/05115-9). Foundation of Research Support of the State of Rio de Janeiro (Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro – FAPERJ) (grant numbers E-26/201.351/2016; E-18/ 2015TXB; E-26/202.862/2018; E 26/010.002477/2016). Foundation of Support for Research and Scientific and Technological Development of Maranhão (Fundação de Amparo à Pesquisa e ao Desenvolvimento Científico e Tecnológico do Maranhão – FAPEMA) (grant number 008/2016). Brazilian Ministry of Health (Ministério da Saúde – MS) (grant number 929698560001160-02). 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) (number grant 2017/10267000531). 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) (grant number 17/2551-0000521-0). 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) and 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) (grant numbers APQ-0172-4.01/16; APQ-0192-4.01/17; APQ0793-4.01/17).Federal University of Pernambuco. Postgraduate Program in Tropical Medicine. Recife, PE, Brazil / University of Pernambuco. Post-Graduation in Health Sciences. Recife, PE, Brazil.University of Pernambuco. Post-Graduation in Health Sciences. Recife, PE, Brazil.London School of Hygiene & Tropical Medicine. Department of Infectious Disease Epidemiology. London, UK.Federal University of Pernambuco. Postgraduate Program in Collective Health. Recife, PE, Brazil.University of Pernambuco. Post-Graduation in Health Sciences. Recife, PE, Brazil.University of Amazonas State. Postgraduate Program in Tropical Medicine. Manaus, AM, Brazil / Doctor Heitor Vieira Dourado Tropical Medicine Foundation. Postgraduate Program in Tropical Medicine. Manaus, AM, Brazil.Ribeirão Preto Medical School. Department of Pediatrics. Ribeirão Preto, SP, Brazil.Ribeirão Preto Medical School. Department of Gynecology and Obstetrics. Ribeirão Preto, SP, Brazil.Ribeirão Preto Medical School. Department of Gynecology and Obstetrics. Ribeirão Preto, SP, Brazil.Ribeirão Preto Medical School. Department of Pediatrics. Ribeirão Preto, SP, Brazil.University of Amazonas State. Postgraduate Program in Tropical Medicine. Manaus, AM, Brazil / Doctor Heitor Vieira Dourado Tropical Medicine Foundation. Postgraduate Program in Tropical Medicine. Manaus, AM, Brazil.University of Amazonas State. Postgraduate Program in Tropical Medicine. Manaus, AM, Brazil / Doctor Heitor Vieira Dourado Tropical Medicine Foundation. Postgraduate Program in Tropical Medicine. Manaus, AM, Brazil.Instituto Fernandes Figueira. Clinical Research Unit. Rio de Janeiro, RJ, Brazil.Oswaldo Cruz Foundation. Instituto Fernandes Figueira. Clinical Research Unit. Rio de Janeiro, RJ, Brazil.Oswaldo Cruz Foundation. Instituto Fernandes Figueira. Obstretics. Rio de Janeiro, RJ, Brazil.University of California. David Geffen School of Medicine. Department of Pediatrics. Los Angeles, CA, Estados Unidos.Oswaldo Cruz Foundation. Research Center Aggeu Magalhães. Recife, PE, Brazil.London School of Hygiene & Tropical Medicine. Department of Infectious Disease Epidemiology. London, UK.Oswaldo Cruz Foundation. Research Center Aggeu Magalhães. Recife, PE, Brazil.Altino Ventura Foundation. Department of Ophthalmology. Recife, PE, Brazil / Pernambuco Eyes Hospital. Recife, PE, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde e Ambiente. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde e Ambiente. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde e Ambiente. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde e Ambiente. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Medicine School of São José do Rio Preto. Department of Infectious Disease. São José do Rio Preto, SP, Brazil.Medicine School of São José do Rio Preto. Department of Infectious Disease. São José do Rio Preto, SP, Brazil.Medicine School of São José do Rio Preto. Department of Gynecology and Obstetrics. São José do Rio Preto, SP, Brazil.Medicine School of Jundiaí. Infectious Pediatric Laboratory. Jundiaí, SP, Brazil.Federal University of São Paulo. Department of Fetal Medicine. São Paulo, SP, Brazil.Father Anchieta University Center. Nursing School. Jundiaí, SP, Brazil.Federal University of São Paulo. Paulista School of Medicine. Departament of Obstetrics. São Paulo, SP, Brazil.Federal University of Goiás. Institute of Tropical Pathology and Public Health. Goiânia, GO, Brazil.Health Secretariat of Goiás State. Maternal and Child Hospital. Goiânia, GO, Brazil.Federal University of São Paulo. Paulista School of Medicine. Departament of Obstetrics. São Paulo, SP, Brazil.Health Secretariat of Goiás State. Maternal and Child Hospital. Goiânia, GO, Brazil.Universidade Federal do Rio Grande do Sul. Hospital das Clinicas de Porto Alegre. Departamento de Genética. Porto Alegre, RS, Brazil.City Hall of Tangará da Serra, Municipal Health Department, Tangará da Serra, MT, Brazil.Federal University of Campina Grande. Medical Academic Unit. Campina Grande, PB, Brazil.Federal University of Campina Grande. Medical Academic Unit. Campina Grande, PB, Brazil.Federal University of Rio de Janeiro. Department of Pediatrics. Rio de Janeiro, RJ, Brazil.D’Or Institute for Research & Education. Department of Pediatrics. Rio de Janeiro, RJ, Brazil.Departmentiversity of Rio de Janeiro Maternity School. Department of Obstectrics. Rio de Janeiro, RJ, Brazil.Departmentiversity of Rio de Janeiro Maternity School. Department of Obstectrics. Rio de Janeiro, RJ, Brazil.Reference Maternity Prof. José Maria de Magalhães Netto. Bahia Health Department, Salvador, BA, Brazil.Oswaldo Cruz Foundation. Gonçalo Moniz Institute. Salvador, BA, Brazil.Oswaldo Cruz Foundation. Gonçalo Moniz Institute. Salvador, BA, Brazil.Federal University of Rio de Janeiro. Department of Infecitous Diseases. Rio de Janeiro, RJ, Brazil.Federal University of Rio de Janeiro. Department of Infecitous Diseases. Rio de Janeiro, RJ, Brazil.Oswaldo Cruz Foundation. Gonçalo Moniz Institute. Salvador, BA, Brazil.Oswaldo Cruz Foundation. Leonidas and Maria Deane Institute. Manaus, AM, Brazil.University of Amazonas State. Postgraduate Program in Tropical Medicine. Manaus, AM, Brazil / Doctor Heitor Vieira Dourado Tropical Medicine Foundation. Postgraduate Program in Tropical Medicine. Manaus, AM, Brazil / Oswaldo Cruz Foundation. Leonidas and Maria Deane Institute. Manaus, AM, Brazil.Oswaldo Cruz Foundation. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brazil.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%

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)