Exposição à teratógenos e anormalidades oculares congênitas em pacientes brasileiros portadores da sequência de Möbius

Purpose: To assess the sociodemographic profiles, teratogen exposures, and ocular congenital abnormalities in Brazilian patients with Möbius sequence. Method: Forty-four patients were recruited from the Brazilian Möbius Sequence Society. This cross-section comprised 41 patients (age, mean ± standard deviation, 9.0 ± 5.5 years) who fulfilled the inclusion criteria. The parent or caregiver answered a questionnaire regarding sociodemographic data and pregnancy history. Patients underwent ophthalmological assessments. They were subdivided into groups according to misoprostol exposure during pregnancy, and the two groups were compared. Results: Mothers/caregivers reported unplanned pregnancies in 36 (88%) cases. Of these, 19 (53%) used misoprostol during their first trimesters. A stable marital status tended to be more frequent in the unexposed group (P=0.051). Incomplete elementary school education was reported by two (11%) mothers in the exposed group and by three (14%) mothers in the unexposed group (P=0.538). The mothers' gestational exposures to cocaine, marijuana, alcohol, and cigarettes were similar in both groups (P=0.297, P=0.297, P=0.428, and P=0.444, respectively). One (5%) case of Rubella infection during pregnancy was found in the unexposed group. The main malformations in the exposed and unexposed groups were the following: strabismus (72% and 77%, respectively), lack of emotional tearing (47% and 36%, respectively), and lagophthalmos (32% and 41%, respectively). Conclusion: Stable marital statuses tended to be more frequent among mothers that did not take misoprostol during pregnancy. Exposures to other teratogens and the main ocular abnormalities were similar in both groups.Objetivo: Descrever o perfil sóciodemográfico, exposição à teratógenos e anormalidades oculares congênitas em pacientes brasileiros portadores da sequência de Möbiu Método: Quarenta e quatro pacientes recrutados da Sociedade Brasileira de Sequência de Möbius foram examinados. Este estudo transversal incluiu 41 pacientes que preencheram os critérios de inclusão do estudo (média das idades: 9,0 ± 5,5 anos). Mãe/responsável dos pacientes responderam a um questionário sobre perfil sóciodemográfico e história gestacional. Foi realizado exame oftalmológico de todos os pacientes. Eles foram agrupados em dois grupos de acordo com a exposição ao misoprostol durante a gestação e seus dados foram comparados. Resultados: Mães/responsáveis referiram gravidez indesejada em 36 (88%) dos casos. Destas, 19 (53%) fizeram uso de misoprostol no primeiro trimestre de gestação. Houve uma tendência do grupo de mães não expostas ao misoprostol de terem um estado civil estável (P=0,051). Duas (11%) mães do grupo de expostas ao misoprostol relataram primeiro grau incompleto e três (14%) do grupo de não expostas (P=0,538). A exposição das mães à cocaína, maconha, álcool e cigarro foi similar em ambos os grupos (P=0,297, P=0,297, P=0,428, P=0,444, respectivamente). Houve um caso (5%) de Rubéola no grupo de mães não expostas. As principais malformações associadas nos pacientes expostos e não expostos foram, respectivamente: estrabismo (72% e 77%), e diminuição da lágrima emocional (47% e 36%) e lagoftalmia (32% and 41%). Conclusão: Estado civil estável foi mais frequente em mães que não fizeram uso de misoprostol durante a gestação. Exposição à outros teratógenos e malformações oculares tiveram distribuição semelhante em ambos os grupos.Fundação Altino Ventura Department of OphthalmologyHospital de Olhos de Pernambuco Department of OphthalmologyUniversity of Illinois Department of Ophthalmology & Visual ScienceUniversidade Federal de São Paulo (UNIFESP) Department of OphthalmologyAssociação de Assistência à Criança DeficienteSanta Casa de Misericórdia de São Paulo Department of OphthalmologyUniversidade de São Paulo Faculdade de Medicina Departments of Neurology and PediatricsUniversidade de São Paulo Instituto de Biociências Department of BiologyUniversidade de São Paulo Department of OphthalmologyUniversidade Federal de Pernambuco Department of Pediatric SurgeryUniversidade de São Paulo Department of PsychiatryServices Group in Epileptic Child PsychiatryInstituto Cema Department of OphthalmologyUNIFESP, Department of OphthalmologySciEL

Endocrine Dysfunction in Children with Zika-Related Microcephaly Who Were Born during the 2015 Epidemic in the State of Pernambuco, Brazil.

Congenital viral infections and the occurrence of septo-optic dysplasia, which is a combination of optic nerve hypoplasia, abnormal formation of structures along the midline of the brain, and pituitary hypofunction, support the biological plausibility of endocrine dysfunction in Zika-related microcephaly. In this case series we ascertained the presence and describe endocrine dysfunction in 30 children with severe Zika-related microcephaly from the MERG Pediatric Cohort, referred for endocrinological evaluation between February and August 2019. Of the 30 children, 97% had severe microcephaly. The average age at the endocrinological consultation was 41 months and 53% were female. The most frequently observed endocrine dysfunctions comprised short stature, hypothyroidism, obesity and variants early puberty. These dysfunctions occurred alone 57% or in combination 43%. We found optic nerve hypoplasia (6/21) and corpus callosum hypoplasia (20/21). Seizure crises were reported in 86% of the children. The most common-and clinically important-endocrine dysfunctions were pubertal dysfunctions, thyroid disease, growth impairment, and obesity. These dysfunctions require careful monitoring and signal the need for endocrinological evaluation in children with Zika-related microcephaly, in order to make early diagnoses and implement appropriate treatment when necessary

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

BACKGROUND: While 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. METHODS: Participants 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. FINDINGS: 376 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

The Microcephaly Epidemic Research Group Paediatric Cohort (MERG-PC): A Cohort Profile.

This cohort profile aims to describe the ongoing follow-up of children in the Microcephaly Epidemic Research Group Paediatric Cohort (MERG-PC). The profile details the context and aims of the study, study population, methodology including assessments, and key results and publications to date. The children that make up MERG-PC were born in Recife or within 120 km of the city, in Pernambuco/Brazil, the epicentre of the microcephaly epidemic. MERG-PC includes children from four groups recruited at different stages of the ZIKV microcephaly epidemic in Pernambuco, i.e., the Outpatient Group (OG/n = 195), the Microcephaly Case-Control Study (MCCS/n = 80), the MERG Pregnant Women Cohort (MERG-PWC/n = 336), and the Control Group (CG/n = 100). We developed a comprehensive array of clinical, laboratory, and imaging assessments that were undertaken by a 'task force' of clinical specialists in a single day at 3, 6, 12, 18 months of age, and annually from 24 months. Children from MCCS and CG had their baseline assessment at birth and children from the other groups, at the first evaluation by the task force. The baseline cohort includes 711 children born between February 2015 and February 2019. Children's characteristics at baseline, excluding CG, were as follows: 32.6% (184/565) had microcephaly, 47% (263/559) had at least one physical abnormality, 29.5% (160/543) had at least one neurological abnormality, and 46.2% (257/556) had at least one ophthalmological abnormality. This ongoing cohort has contributed to the understanding of the congenital Zika syndrome (CZS) spectrum. The cohort has provided descriptions of paediatric neurodevelopment and early epilepsy, including EEG patterns and treatment response, and information on the frequency and characteristics of oropharyngeal dysphagia; cryptorchidism and its surgical findings; endocrine dysfunction; and adenoid hypertrophy in children with Zika-related microcephaly. The study protocols and questionnaires were shared across Brazilian states to enable harmonization across the different studies investigating microcephaly and CZS, providing the opportunity for the Zika Brazilian Cohorts Consortium to be formed, uniting all the ZIKV clinical cohorts in Brazil

Resposta humoral ao vírus dengue em mães/filhos: relação com a sequência de Möbius Humoral immune response to dengue virus in mothers/children: relation with Möbius sequence

OBJETIVO: Investigar a resposta humoral para o vírus dengue em pacientes com sequência de Möbius e suas mães, analisando a relação entre a infecção na gestação e o nascimento de portadores da sequência de Möbius. MÉTODOS: Foram revisados os prontuários dos pacientes atendidos em centro de referência. Aplicou-se um questionário estruturado a cada genitora. Sorologia por Elisa para IgG de dengue foi efetuada em 35 pacientes e suas mães. O teste de neutralização por redução em placas foi feito nas que referiram infecção viral na gestação e em seus filhos, para determinar o sorotipo viral causador da infecção. RESULTADOS: Febre, cefaléia e/ou dor retro-orbitária foi referida por 18 (51,4%) mães. Três (8,6%) referiram dengue no primeiro ou início do segundo trimestre de gestação. Cruzando-se as informações das sorologias das mães e crianças observou-se que em 57,1% dos casos há positividade sorológica para o vírus do dengue na mãe e no filho. Das três mães com infecção na gestação, uma e seu filho, apresentou teste de neutralização por redução em placa positivo para o vírus dengue tipo três (DENV-3), entretanto o sorotipo apenas foi introduzido em Pernambuco em 2002, o que exclui a possibilidade de ter ocorrido transmissão vertical da doença. CONCLUSÃO: As sorologias dos casos que tiveram diagnóstico clínico de dengue na gravidez revelaram-se incompatíveis com a hipótese de ter ocorrido transmissão vertical da doença. Portanto, na amostra estudada, a infecção pelo vírus do dengue não pode ser considerada como fator implicado na gênese da sequência de Möbius.<br>PURPOSE: To investigate the humoral immune response to dengue virus in patients with Möbius sequence and their mothers, assessing the relation between this infection during pregnancy and Möbius sequence. METHODS: The medical records were reviewed, and a questionnaire was answered by each mother. IgG ELISA was performed in 35 patients and their mothers. A plaque reduction neutralization test was further done in the mothers who reported a viral infection during pregnancy and in their children for determining which dengue serotype virus had caused the infection. RESULTS: Fever, headache and/or retrobulbar pain during pregnancy was referred by eighteen (51.4%) mothers. Three (8.6%) reported dengue during the first or second quarteers of pregnancy. When cross analyzing the mothers and their respective children serological results, 57.1% of them matched. Of the three mothers with clinical diagnosis of viral infection during pregnancy, one and its respective children had a positive plaque reduction neutralization test for dengue serotype three (DENV-3), this serotype reached Pernambuco in 2002, which excludes the possibility of a vertical transmission to the children. CONCLUSION: The serology of the cases that had clinical diagnosis of dengue during pregnancy proved to be incompatible with the hypothesis of the disease vertical transmission. Therefore, in the present serie, the dengue virus infection can not be considered as a factor involved in the genesis of Möbius sequence

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)

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%

Characterisation of microbial attack on archaeological bone

As part of an EU funded project to investigate the factors influencing bone preservation in the archaeological record, more than 250 bones from 41 archaeological sites in five countries spanning four climatic regions were studied for diagenetic alteration. Sites were selected to cover a range of environmental conditions and archaeological contexts. Microscopic and physical (mercury intrusion porosimetry) analyses of these bones revealed that the majority (68%) had suffered microbial attack. Furthermore, significant differences were found between animal and human bone in both the state of preservation and the type of microbial attack present. These differences in preservation might result from differences in early taphonomy of the bones. © 2003 Elsevier Science Ltd. All rights reserved