Metabolomics applied to maternal and perinatal health : a review of new frontiers with a translation potential

The prediction or early diagnosis of maternal complications is challenging mostly because the main conditions, such as preeclampsia, preterm birth, fetal growth restriction, and gestational diabetes mellitus, are complex syndromes with multiple underlying mechanisms related to their occurrence. Limited advances in maternal and perinatal health in recent decades with respect to preventing these disorders have led to new approaches, and “omics” sciences have emerged as a potential field to be explored. Metabolomics is the study of a set of metabolites in a given sample and can represent the metabolic functioning of a cell, tissue or organism. Metabolomics has some advantages over genomics, transcriptomics, and proteomics, as metabolites are the final result of the interactions of genes, RNAs and proteins. Considering the recent “boom” in metabolomic studies and their importance in the research agenda, we here review the topic, explaining the rationale and theory of the metabolomic approach in different areas of maternal and perinatal health research for clinical practitioners. We also demonstrate the main exploratory studies of these maternal complications, commenting on their promising findings. The potential translational application of metabolomic studies, especially for the identification of predictive biomarkers, is supported by the current findings, although they require external validation in larger datasets and with alternative methodologies

Imunogenicidade das vacinas contra febre amarela WHO-17D e 17DD: ensaio randomizado

OBJECTIVE: To compare the immunogenicity of three yellow fever vaccines from WHO-17D and Brazilian 17DD substrains (different seed-lots). METHODS: An equivalence trial was carried out involving 1,087 adults in Rio de Janeiro. Vaccines produced by Bio-Manguinhos, Fiocruz (Rio de Janeiro, Brazil) were administered following standardized procedures adapted to allow blocked randomized allocation of participants to coded vaccine types (double-blind). Neutralizing yellow fever antibody titters were compared in pre- and post-immunization serum samples. Equivalence was defined as a difference of no more than five percentage points in seroconversion rates, and ratio between Geometric Mean Titters (GMT) higher than 0.67. RESULTS: Seroconversion rates were 98% or higher among subjects previously seronegative, and 90% or more of the total cohort of vaccinees, including those previously seropositive. Differences in seroconversion ranged from -0.05% to -3.02%. The intensity of the immune response was also very similar across vaccines: 14.5 to 18.6 IU/mL. GMT ratios ranged from 0.78 to 0.93. Taking the placebo group into account, the vaccines explained 93% of seroconversion. Viremia was detected in 2.7% of vaccinated subjects from Day 3 to Day 7. CONCLUSIONS: The equivalent immunogenicity of yellow fever vaccines from the 17D and 17DD substrains was demonstrated for the first time in placebo-controlled double-blind randomized trial. The study completed the clinical validation process of a new vaccine seed-lot, provided evidence for use of alternative attenuated virus substrains in vaccine production for a major manufacturer, and for the utilization of the 17DD vaccine in other countries.OBJETIVO: Comparar a imunogenicidade de três vacinas contra febre amarela ) das subcepas WHO-17D e 17DD brasileira (diferentes lotes-semente). MÉTODOS: Trata-se de ensaio de equivalência envolvendo 1.087 adultos no Rio de Janeiro, RJ. As vacinas foram produzidas em Bio-Manguinhos, Fiocruz (Rio de Janeiro, Brasil) e foram administradas seguindo procedimentos adaptados para randomização em blocos, com tipos de vacinas codificados ("duplo-cego"). Anticorpos neutralizantes contra febre amarela foram dosados antes e depois da vacinação. Definiu-se equivalência como diferença nas taxas de soroconversão não superior a cinco pontos percentuais, e razão de títulos médios geométricos superior (TMG) a 0,67. RESULTADOS: As taxas de soroconversão foram iguais ou maiores do que 98% nos participantes previamente soronegativos. Na coorte completa (incluindo os previamente soropositivos) a soroconversão foi igual ou superior a 90%. As diferenças na soroconversão variaram de -0,05% a -3,02% entre os grupos de comparação. A intensidade da resposta imune também foi semelhante nos grupos: 14,5 UI/mL a 18,6 UI/mL. As razões de TMG variaram de 0,78 a 0,93. Considerando o grupo placebo, as vacinas explicaram 93% da soroconversão. Viremia foi detectada entre os dias três e sete em 2,7% dos participantes vacinados. CONCLUSÕES: A equivalência na imunogenicidade das vacinas contra a febre amarela das subcepas 17D e 17DD foi demonstrada pela primeira vez em ensaio clínico randomizado, duplo-cego, controlado com placebo. O estudo completou o processo de validação clínica do novo lote-semente de vacina, além de ampliar as bases para utilização da vacina brasileira em outros países e de trazer alternativas de subcepas para o produtor da vacina no Brasil

Infecção pelo Parvovírus Canino em filhotes com gastrenterite em Niterói, Rio de Janeiro, Brasil de 1995 a 1997

Amostras fecais de cães com gastrenterite, até 6 meses de idade, foram testadas para a presença do parvovírus canino (CPV-2) pela reação de hemaglutinação (HA) e confirmadas pela reação de inibição da hemaglutinação (HI). Quarenta das 79 amostras, recebidas no período de abril de 1995 a junho de 1997, foram consideradas positivas. Aproximadamente 70% destas amostras foram obtidas de animais entre 2 e 4 meses de idade, época em que o risco de contraírem a infecção pelo CPV-2 é alto apesar da vacinação. Nenhuma variação sazonal da infecção pelo parvovírus canino pôde ser observada, e um estudo retrospectivo realizado na PolVet - UFF mostrou que em um período de 6 anos (1991-97), casos de gastrenterite ocorreram durante todos os anos em Niterói, sem uma sazonalidade definida.Fecal samples from puppies with gastroenteritis less than 7 months old were examined for canine parvovirus infection (CPV-2) by hemagglutination (HA) and subsequent hemagglutination-inhibition (HI) tests. Forty of the 79 samples collected from April 1995 to June 1997 were found to be positive. About 70% of these samples were from 2 to 4 months old puppies, age in which they are at increased risk of developing CPV-2 infection, despite of vaccination. No seasonal distribution of canine parvovirus cases was found and it was supported by the results of a retrospective study realized at PolVet-UFF, which showed that gastroenteritis cases occurred throughout the year, for a six-year period (1991-97) in Niterói, Rio de Janeiro

Planning, implementing, and running a multicentre preterm birth study with biobank resources in Brazil : the preterm SAMBA study

Background. Our aim was to describe the steps in planning, implementing, and running a multicentre cohort study of maternal and perinatal health using a high-quality biobank comprised of maternal serum, plasma, and hair samples collected from five sites in Brazil.The Preterm SAMBA study, conducted by the Brazilian Network for Studies on Reproductive and Perinatal Health, was an innovative approach used to identify women at higher risk for preterm birth. It is also of great importance in the study of other maternal and perinatal complications in the context of Brazil, which is a middle-income country. Methods. We described phases of planning, implementing, and running the Preterm SAMBA study, a multicentre Brazilian cohort study of low-risk nulliparous pregnant women, to validate a set of metabolite biomarkers for preterm birth identified in an external cohort. Procedures and strategies used to plan, implement, and maintain this multicentre preterm birth study are described in detail. Barriers and experience cited in the current narrative are not usually discussed in the scientific literature or published study protocols. Results. Several barriers and strategies were identified in different phases of the Preterm SAMBA study at different levels of the study framework (steering committee; coordinating and local centres). Strategies implemented and resources used in the study are a legacy of the Brazilian Network, aimed at training collaborators in such complex settings. Conclusion. The Brazilian Network for Studies on Reproductive and Perinatal Health has gained some experience in conducting a multicentre cohort study using a resourceful biobank which may be helpful to other research groups and maternal/perinatal health networks that plan on employing a similar approach to a similar background

Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure <= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt