PRE-EMPT (PRE-eclampsia-Eclampsia Monitoring, Prevention & Treatment)
We have been funded by the Bill & Melinda Gates Foundation (BMGF) to lead an international initiative designed to reduce the burden of pre-eclampsia through community-level prevention, case identification and monitoring, and treatment. PRE-EMPT has five component studies.
The first is a clinical trial to determine if increased calcium intake prior to and during the first half of pregnancy reduces the risk of developing pre-eclampsia.
Secondly, we will modify the PIERS model (see below) to develop and validate the miniPIERS model, which is symptom and signed-based, for use in rural and remote communities and low and middle income countries. The miniPIERS project has the support of the BMGF, WHO, USAID and the CIHR, and is taking place in Brazil, China, Fiji, Pakistan, South Africa, and Uganda.
Third, we will incorporate the miniPIERS model into the CLIP (Community Level Intervention for Pre-eclampsia) package of care. This package of care will empower specifically trained community health workers to better identify women with pre-eclampsia, accelerate their transfer to effective care, and intervene with proven therapies to reduce the risks of seizures and stroke.
Fourth, we will convene an international data and biological sample collaboration – the Pre-eclampsia CoLaboratory – that will facilitate new knowledge generation and rapidly increase our ability to intervene to avoid the adverse outcomes of pre-eclampsia.
Fifth, we will support the WHO as it updates its international guidelines to improve the care of women with pre-eclampsia and other forms of pregnancy hypertension.
PIERS (Pre-eclampsia Integrated Estimate of RiSk)
We are investigating a range of potential predictors of adverse maternal outcomes in women admitted to hospital with pre-eclampsia. With CIHR support and in collaboration with the World Health Organization (WHO), fullPIERS is for use in well-resourced settings and was developed and validated in tertiary units in Canada, New Zealand, Australia, and the UK in women with pre-eclampsia. fullPIERS now requires external validation, which is underway. The second version, of the PIERS model, miniPIERS, is discussed above (PRE-EMPT).
Recently, in collaboration with Mark Ansermino (co-PI) and Guy Dumont, we received a Saving Lives at Birth seed grant for the project, PIERS on the Move, whereby we will develop a cell phone-based pulse oximeter, sphygmomanometer and decision aid for use by community health workers in low and middle income countries. As pulse oximetry is a powerful component of fullPIERS, we anticipate that the phone oximeter will transform miniPIERS into a model that approximates fullPIERS in diagnostic and stratification performance.
THE IMMUNOLOGY OF THE FETO-MATERNAL INTERFACE
We are investigating the interaction between first trimester extravillous trophoblast (EVT) and decidual natural killer cells (dNK) using a novel ex vivo model of placentation. In this model we co-culture either maternal immune cells, dNK, or their conditioned medium, with either villous tip explants, isolated EVT, or an EVT-derived cell line, to examine the key interactions that appear to modulate the success or relative/complete failure of EVT invasion. We have determined that dNK limit EVT migration while appearing to promote EVT neovasculogenesis. These interactions underlie the quality of placentation and the risk of subsequent placental complications in pregnancy.