Assessing the risks for stillbirth in São Paulo, Brazil: protocol for a multidisciplinary case-control study - FetRisks.

Stillbirth is a fundamental component of childhood mortality, but its causes are still insufficiently understood. This study aims to explore stillbirth risk factors by using a multidisciplinary approach to stimulate public policies and protocols to prevent stillbirth, improve maternal care and support bereaved families. METHODS AND ANALYSIS: In this case-control study with stillbirths and live births in 14 public hospitals in São Paulo, mothers are interviewed at hospitals after delivery, and hospital records and prenatal care registries are reviewed. Maternal and umbilical cord blood samples and placentas are collected to analyse angiogenesis and infection biomarkers, and the placenta's anatomopathological exam. Air pollutant exposure is estimated through the participant's residence and work addresses. Traditional and non-invasive autopsies by image-guided histopathology are conducted in a subset of stillbirths. Subsample mothers of cases are interviewed at home 2 months after delivery on how they were dealing with grief. Information contained in the official prenatal care registries of cases and controls is being compiled. Hospital managers are interviewed about the care offered to stillbirth mothers. Data analysis will identify the main risk factors for stillbirth, investigate their interrelations, and evaluate health services care and support for bereaved families. We hope this project will contribute to the understanding of stillbirth's risk factors and related health services in Brazil, providing new knowledge about this central public health problem, contributing to the improvement of public policies and prenatal and puerperal care, helping to prevent stillbirths and improve the healthcare and support for bereaved families. ETHICS AND DISSEMINATION: This study protocol was approved by the Ethics Committee of the Municipal Health Secretary (process no 16509319.0.3012.5551) and of the Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (process no 16509319.0.0000.0068). Results will be communicated to the study participants, policy-makers and the scientific community.

Individual exposure to urban air pollution and its correlation with placental angiogenic markers in the first trimester of pregnancy, in São Paulo, Brazil.

Pollution of the atmosphere is known that may lead to adverse obstetric outcomes, including fetal growth restriction, gestational hypertension, and preeclampsia. Such disorders are correlated with imbalances in angiogenic factors, which may also be involved in the pathological mechanism as the pollutants impact placental and maternal physiology. In the first trimester of gestation, this study assessed the outcomes of personal maternal short period exposure to air pollution on soluble fms-like tyrosine kinase 1 (sFlt1) and placental growth factor (PLGF) of pregnant women blood concentrations. This was a cross-sectional study, held in the city of São Paulo, Brazil, and conducted with low-risk pregnant women, who carried personal passive nitrogen dioxide (NO2) and ozone (O3) monitors for about a few days preceding the ultrasound evaluation, and on this day, the venous blood sample was collected to measure the angiogenic factors sFlt1 and PLGF and their ratio (sFlt1/PLGF) by enzyme-linked immunosorbent assay (ELISA). By means of multiple regression models, the effect of the studied pollutants on the log-transformed concentrations of the angiogenic factors was evaluated. One hundred thirty-one patients were included. The log of the sFlt1/PLGF ratio increased with rising NO2 levels (p = 0.021 and beta = 0.206), and the log of the PLGF concentration showed a negative correlation with NO2 (p = 0.008 and beta = - 0.234). NO2, an indicator of the levels of primary air pollutants, presented significant positive correlation with an increased sFlt1/PLGF ratio and diminished PLGF levels, which may reflect an antiangiogenic state generated by air pollution exposure.

Preditores moleculares de evolução da mola hidatiforme no tecido trofoblástico / Molecular prognostic predictors in trophoblastic tissue of hydatidiform mole

A mola hidatiforme (MH) é a forma mais comum de doença trofoblástica gestacional e representa uma condição benigna que em alguns casos pode sofrer malignização. Todas as pacientes diagnosticadas com doenças molares são acompanhadas por pelo menos seis meses para detecção precoce da neoplasia trofoblástica gestacional. No momento, existem poucas ferramentas para avaliação prognóstica da mola hidatiforme. Foi descrita a expressão diferencial de diversos fatores em tecido molar em comparação ao trofoblasto não neoplásico. Essas moléculas podem estar relacionadas com o comportamento agressivo da MH e consequentemente poderiam servir para melhor entendimento do processo de malignização e como preditoras da evolução da doença trofoblástica gestacional.

The hydatidiform mole (HM) is the most common form of gestational trophoblastic disease and a benign condition that in some cases may undergo malignant transformation. All patients diagnosed with molar diseases are monitored for at least six months for early detection of gestational trophoblastic neoplasia. Currently, there are few prognostic tools for the prediction of hydatidiform mole evolution. Differential expression on molar tissue of different molecular factors have been described when compared to non-neoplastic trophoblast. These markers may be associated with aggressive behavior of HM and therefore could serve as predictors of the development of gestational trophoblastic disease and to better understand molar malignant transformation. This review article will summarize and evaluate prognostic molecular markers of HM.

NADPH oxidase as an important source of reactive oxygen species at the mouse maternal-fetal interface: putative biological roles.

Oxygen derivatives that comprise the large family of reactive oxygen species (ROS) are actively involved in placental biology. They are generated at the maternal-fetal interface at the level of decidual, trophoblast and mesenchymal components. In normal conditions, ROS produced in low concentrations participate in different functions as signalling molecules, regulating activation of redox-sensitive transcription factors and protein kinases involved in cell survival, proliferation and apoptosis, hence much of cell functioning. Physiological ROS generation is also associated with such defence mechanisms as phagocytosis and microbiocidal activities. In mice, particularly but not exclusively, trophoblast cells phagocytose intensively during implantation and post-implantation periods and express enzymic machinery to address a ROS-producing response to changes in the environment. The cells directly associated with ROS production are trophoblast giant cells, which mediate each and every relationship with the maternal organism. In this review, the production of ROS by the implanting mouse trophoblast is discussed, focusing on NADPH oxidase expression, regulatory mechanisms and similarities with NOX2 from phagocytes. Some of the current controversies are assessed by attempting to integrate data from studies in human trophoblast and mouse models.