• Pre-eclampsia / Hypertension in pregnancy / IUGR
• Th2 pregnancy immunology / Infection & atherosis
• Clinical epidemiology / Health services research
• Flow cytometry / Cell & molecular biology / Translational research

Pre-eclampsia ('toxaemia' of pregnancy; high blood pressure and the loss of protein in the urine) is the most common cause of maternal death in North America, and the second leading cause of maternal death globally. It also causes an excess burden of illness and death for fetuses, especially when pregnancies are affected remote from term. The process of pre-eclampsia seems to involve inappropriate activation of the immune system, causing inflammation and organ damage.

We are investigating what aspect of the inflammatory response is specific to pre-eclampsia, how to quantify the multi-organ consequences of that inflammatory response, and how to modify the response to safely prolong pregnancies affected remote from term and to accelerate the recovery from the inflammation postnatally. In low and middle income countries, we are investigating community-level interventions to improve monitoring, prevention and treatment of women with pre-eclampsia to reduce the burden of life-ending, life-altering, and life-threatening events that complicate the pregnancies of these women.

In addition, we are studying the relationship between a woman’s immune cells in the womb (uterus) and the successful formation of the afterbirth (placenta).

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.

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.

von Dadelszen P, Payne B, Menzies JM, Li J, Ansermino JM, Broughton Pipkin F, Côté AM, Douglas MJ, Gruslin A, Hutcheon JA, Joseph KS, Kyle PM, Lee T, Loughna P, Merialdi M, Millman AL, Moore MP, Moutquin JM, Ouellet AB, Smith GN, Walker JJ, Walley KR, Walters BN, Widmer M, Lee SK, Russell JR, Magee LA, for the PIERS Study Group. Predicting adverse maternal outcomes in pre-eclampsia: the fullPIERS (Pre-eclampsia Integrated Estimate of RiSk) model – development and validation. Lancet 2011;377:219-227. PMID: 21185591

von Dadelszen P, Sawchuck D, McMaster R, Douglas MJ, Joseph KS, Lee SK, Mitton C, Saunders S, Liston RM, Magee LA, for the TESS (Translating Evidence-based Surveillance and treatment Strategies) Group. The active implementation of pregnancy hypertension guidelines in British Columbia. Obstet Gynecol 2010;116:659-666. PMID: 20733449

Steegers EAP, von Dadelszen P, Duvekot JJ, Pijnenborg R. Seminar: pre-eclampsia. Lancet 2010;376:631-6442010 (Epub ahead of print). PMID: 20598363

Hu Y, Eastabrook G, Tan R, MacCalman CD, Dutz JP, von Dadelszen P. Decidual NK cell-derived conditioned medium enhances capillary tube and network organization in an extravillous cytotrophoblast cell line through up-regulation of ICAM-1 expression. Placenta 2010;31:213-221. PMID: 20080299

Xie F, Hu Y, Turvey SE, Magee LA, Brunham RC, Choi KC, Krajden M, Leung PCK, Money DM, Patrick DM, Thomas E, von Dadelszen P. Toll-like receptors 2 and 4 and the cryopyrin inflammasome in normal pregnancy and pre-eclampsia. BJOG 2010;117:99-108. PMID: 20002372

Côté AM, von Dadelszen P, Brown MA, Firoz T, Lam EM, Liston RM, Magee LA. The urinary spot protein/creatinine ratio is a reasonable diagnostic test for proteinuria in hypertensive pregnancy: systematic review. BMJ 2008;336:1003-1006. PMID: 18403498

Menzies J, Magee LA, MacNab YC, Li J, Yin R, Stuart H, Baraty B, Lam E, Hamilton T, Lee SK, von Dadelszen P for the Pre-eclampsia Integrated Estimate of RiSk (PIERS) Study Group. Instituting surveillance guidelines and adverse outcomes in preeclampsia. Obstet Gynecol 2007;110:121-127. PMID: 17601906

Hu Y, Dutz R, Tan R, MacCalman C, Yong P, von Dadelszen P. Decidual natural killer cells alter in vitro first trimester extravillous cytotrophoblast migration; a role for interferon-gamma. J Immunol 2006:177 8522-8530. PMID: 17142750

Magee LA, Cham C, Waterman EJ, Ohlsson A, von Dadelszen P. Hydralazine for treatment of severe hypertension in pregnancy: meta-analysis. BMJ 2003;327:955-960. PMID: 14576246

von Dadelszen P, Ornstein MP, Bull SB, Logan AG, Koren G, Magee LA. Fall in mean arterial pressure and fetal growth restriction in pregnancy hypertension: a meta-analysis. Lancet 2000;355:87-92 (PMID: 10675164). PMID: 10675164

Magee LA, Ornstein MP, von Dadelszen P. Fortnightly review. The management of hypertension in pregnancy. BMJ 1999; 318:1332-1336. PMID: 10323823

2012 CIHR Planning Grant for Community Level Interventions for Pre-eclampsia and Geographic Information Systems (GIS)