Maternal blood pressure associates with placental DNA methylation both directly and through alterations in cell-type composition.

BACKGROUND: Maternal blood pressure levels reflect cardiovascular adaptation to pregnancy and proper maternal-fetal exchanges through the placenta and are very sensitive to numerous environmental stressors. Maternal hypertension during pregnancy has been associated with impaired placental functions and with an increased risk for children to suffer from cardiovascular and respiratory diseases later on. Investigating changes in placental DNA methylation levels and cell-type composition in association with maternal blood pressure could help elucidate its relationships with placental and fetal development. METHODS: Taking advantage of a large cohort of 666 participants, we investigated the association between epigenome-wide DNA methylation patterns in the placenta, measured using the Infinium HumanMethylation450 BeadChip, placental cell-type composition, estimated in silico, and repeated measurements of maternal steady and pulsatile blood pressure indicators during pregnancy. RESULTS: At the site-specific level, no significant association was found between maternal blood pressure and DNA methylation levels after correction for multiple testing (false discovery rate < 0.05), but 5 out of 24 previously found CpG associations were replicated (p-value < 0.05). At the regional level, our analyses highlighted 64 differentially methylated regions significantly associated with at least one blood pressure component, including 35 regions associated with mean arterial pressure levels during late pregnancy. These regions were found enriched for genes implicated in lung development and diseases. Further mediation analyses show that a significant part of the association between steady blood pressure-but not pulsatile pressure-and placental methylation can be explained by alterations in placental cell-type composition. In particular, elevated blood pressure levels are associated with a decrease in the ratio between mesenchymal stromal cells and syncytiotrophoblasts, even in the absence of preeclampsia. CONCLUSIONS: This study provides the first evidence that the association between maternal steady blood pressure during pregnancy and placental DNA methylation is both direct and partly explained by changes in cell-type composition. These results could hint at molecular mechanisms linking maternal hypertension to lung development and early origins of childhood respiratory problems and at the importance of controlling maternal blood pressure during pregnancy.

A systematic review on ethical challenges of 'field' research in low-income and middle-income countries: respect, justice and beneficence for research staff?

INTRODUCTION: Primary data collection in low-income and middle-income countries (LMICs) is associated with a range of ethical complexities. Considerations on how to adequately ensure the well-being of research staff are largely neglected in contemporary ethics discourse. This systematic review aims to identify the ethical challenges that research staff across different hierarchical levels and scientific disciplines face when conducting research in LMICs. METHODS: We searched 13 electronic databases and handsearched publications in six selected journals as well as the reference lists of all included studies. No restrictions were applied with respect to the publication date, research design, and target population. RESULTS: 23 151 studies were retrieved, 183 of which met our inclusion criteria. We identified nine different types of ethical challenges that research staff may be exposed to during field research, including (1) role conflicts that can emerge from participants' help requests and the high level of deprivation found in certain study settings, (2) feelings of guilt and (3) detrimental mental health impacts. Further challenges were (4) sexual harassment (5) safety risks and (6) political repression, particularly in postconflict, disaster-ridden or autocratic study contexts. Additionally, studies reported (7) inadequate working conditions and (8) power imbalances within research teams, while (9) ethics boards were found to be ill equipped to anticipate and address emerging risks, thus increasing the ethical liability of researchers. CONCLUSION: This review revealed several complex ethical challenges that research staff may face during data collection. In order to achieve the Sustainable Development Goal 8.8 on 'safe and secure working environments' and to protect research staff from harm, amendments must urgently be made to current ethical standards. PROSPERO REGISTRATION NUMBER: CRD42019131013.