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Objective 4: Global Pregnancy Collaboration (update from June-July 2017)

2017 CoLab Annual Membership Meeting:

Planning and preparations continue for the CoLab annual membership meeting to be held October 2-3, 2017 as part of the large PRE-EMPT Sixth Annual Meeting at the Sheraton Heathrow Hotel in London, United Kingdom. The Planning Committee has selected the Scientific Workshop theme: "Prepregnancy and pregnancy nutrition". Speakers have been invited and the Agenda is in preparation. Topics include: (1) Undernutrition-micronutrients; (2) Obesity: Mechanisms in different populations and Insulin resistance; (3) Salt in pregnancy; (4) Calcium in pregnancy; (5) Nutrition and DOHAD; (6) Vitamin D; and (7) Interventions: the challenges in LMIC (Panel Discussion).

 
Potential Consortium and COLLECT in Indonesia:

CoLab members Jim Roberts, Chris Redman and Annetine Staff will visit Indonesia (by invitation) in October 2017 to address the formation of an Indonesian consortium similar to the group we are supporting in Latin America. We will also encourage the use of the COLLECT Medical Birth Registry in this setting. We have also begun exploring the possibility of a similar arrangement with investigators in Africa and India.

 

Project Highlights:

PREDICTV (PReclampsia Early Determination for Intervention, Cure, and Therapeutics by Vasopressin) PI: Mark Santillan, MD, PhD

The University of Iowa, American Heart Association funded PREDICTV (PReclampsia Early Determination for Intervention, Cure, and Therapeutics by Vasopressin), focused on verifying copeptin as a first trimester, robust plasma and urine biomarker for preeclampsia, relies on a collaboration of many CoLab groups.  Initial urine predictive studies, presented at the national SMFM meeting relied on cohorts from Boston (Lifecodes, PI: Thomas McElrath MD, PhD) and Seattle (GAPPS cohort).  This study is now expanding internationally with collaboration with Sarah Manyame, MD (University of Zimbabwe) and Gustav Dekker MD, PhD (University of Adelaide) to share clinical data and samples.  This arm of the study has close to 1500 participants.  Collaboration with CoLab has extended beyond strictly research.  Mark Santillan from Iowa was the Session Co-Chair and organizer of a special American Physiological Society session at Experimental Biology 2017 entitled "Novel genetic risk factors and early-pregnancy mechanisms contributing to preeclampsia."  James Roberts, MD was the keynote speaker for the event and he brought translational, physiologic and clinical relevance to the well-attended session.

 

Linking Fertility (IVF) and Early Pregnancy / Prepregnancy Repository Linkage: Co-Principal Investigators: Thomas McElrath, MD and Mark Santillan, MD

This is a collaborative project of two CoLab members Mark Santillan (University of Iowa) and Thomas McElrath (Harvard University). Currently, they have linked their IVF and pregnancy registries and have the ability to follow 400+ pregnancies from pre-pregnancy through delivery and are now co-developing this biorepository with CoLab members. They are investigating the effects of trophectodermal manipulation on placentation and pregnancy outcome. They plan to reconvene at the 2017 CoLab annual meeting.

 

Microparticle Proteomics as a Marker for Impending Preterm Birth: PI: Thomas McElrath, MD

This project seeks to validate existing work indicating the ability to predict spontaneous preterm birth using the protein signature of microparticles gathered at 12 weeks gestation. We have been able to recruit multiple samples though CoLab partners including GAPPS and Magee Womens Hospital. The confirmatory results are highly encouraging and were presented as a poster at the 2017 SRI Conference. We will present additional results at the 2017 annual CoLab meeting. Samples are presently under analysis with manuscripts in preparation. We anticipate examining the exosomal proteome for preeclampsia related markers as well.

 

Sisters and Daughters of Women with Preeclampsia: A Cohort Study: Principal Investigators: Hilary S. Gammill, MD; Roberta Ness, MD, MPH; James M. Roberts, MD; Eleni Tsigas.  Co-investigators: Alina Brewer; Kasey Dickenson; Ingrid Granne, PhD; Chris Redman, MD.

CoLab is supporting and working with The Preeclampsia Registry (TPR) to ascertain the feasibility of conducting a large-scale cohort study of sisters and daughters of women with preeclampsia.  The overarching goal of this line of investigation is to determine whether preeclampsia directly causes cardiovascular disease or whether both arise from shared risk factors.  Studies of women at risk for preeclampsia before their first pregnancy provide a unique opportunity to definitively answer this question.  The feasibility study will evaluate the ability of TPR in conjunction with its communication partners, to enroll and maintain engagement of nulliparous sisters or daughters of women with a history of preeclampsia (and controls).

Since receiving funding in March 2017, TPR has been focused on performing an upgrade of TPR’s mobile capabilities and user interface.  This will be key for successful enrollment, engagement, and follow-up.  Marketing and recruitment strategies are being developed with PF’s communication partner, BabyCenter, which reaches more than 45 million parents per month online.  The protocol modification, consent forms, and questionnaires are being drafted for IRB review in July 2017.  It is anticipated that recruitment for this study will begin in August 2017.

 

EMPOWER:

Dr. Sarah Manyame, our LMIC representative working in Zimbabwe was awarded an EMPOWER grant for her project, “Urine biomarkers for preeclampsia in high-risk women”. Cosponsored by the ISSHP, CoLab and the Board of Directors of the Preeclampsia Foundation, this EMPOWER award will provide funding and mentoring for beginning investigators in LMIC.  Her project is to investigate concentrations of PlGF/sFlt-1, protein/creatinine ratios, calcium/creatinine ratios, and SERPINA-1 measured by Congo Red in the urine of hypertensive women in pregnancy. This work will be performed as a nested cohort study within the CAP Trial, and could provide a simple and inexpensive way to identify preeclamptic women in LMICs. Her mentor, Jim Roberts, recently visited Sarah during which time they created a timeline and began plans for performing these studies in Harare.  They also visited Carmen Swanepoel who administers the CoLab African Biobank at the Tygerberg medical branch of Stellenbosch University. They examined the facility and began the exploration of the extension of Sarah’s study with a validation cohort with collaborators in Cape Town.

 

PRE-PARE Brazil:  

The intervention component of PREPARE is underway as is the assembly of the cohort for a 7000 subject biobank.  Several challenges have been overcome and the study is underway. Plans are evolving for an April 2018 meeting of the Brazil and CoLab groups.

 

Funding News:

PRECISE (PREgnancy Care Integrating translational Science, Everywhere) Network: a sub-Saharan network for placental disorders:

Several CoLab resources including the COLLECT database, consortium biological samples and the standardized protocol for placental sampling and tissue storage (Optimising sample collection for placental research, GJ Burton, et al; Placenta35 (2014) 9-22) will be utilized in this proposal submitted by Peter von Dadelszen and colleagues to the GCRF, which was recently funded. In a letter from Jim Roberts in support of the project and on behalf of the CoLab, he invites the PRECISE consortium to CoLab membership.

 

All Children Thriving: South Africa (ACT):

The biorepository in South Africa has become a reality. CoLab partnered with the PRE-EMPT CAP study to work with Life Assay Diagnostics to field test an inexpensive protein/creatinine test strip for use in the field. As part of this project study samples and future samples from Africa will be stored at a world-class biobank (Stellenbosch University H3 biobank). This center will also be used to store samples from the CAP study.


Recent Conferences and Presentations:

2nd Research Meeting on Innovation in Vascular Health, Chillán, Chile, July 6, 2017 and 4th Hypertension in Pregnancy Meeting July 7, 2017: These international meetings organized by CoLab member Carlos Escudero were attended by nearly 100 researchers from Argentina, Brazil, Chile, Colombia, Cuba, Mexico and the USA including many members of the Iberoamerican Adverse Pregnancy Network. The group is enthusiastic and interested in collaboration. Several members inquired about assistance in grant preparation and Jim offered CoLab support.   Jim Roberts was keynote speaker at the Hypertension in Pregnancy meeting, July 7th; his presentation entitled: Predictors of Preeclampsia: Now and in the Future. Drs. Roberts, Redman, Jeyabalan and Ms. Dickenson also presented a WebEx overview of COLLECT and the upcoming registry to IT staff at the hospital in Chillán.

 

Select Member Updates:

The Preeclampsia Registry (TPR) (Alina Brewer (Research Coordinator) and Eleni Tsigas Principal Investigator):

TPR currently has 3,460 participants enrolled, including women affected by preeclampsia, their family members, and controls. General Participant Information: (a) 326 provided at least one health update; (b) 570 DNA samples were collected (228 affected women, 260 offspring, 34 sisters, 2 mothers, 46 partners); (c) 192 affected samples completed exome sequencing.  Data will be made available to approved secondary researchers after initial publications complete; (d) There are 7 ongoing or future studies using TPR data and/or biological samples, 1 completed study; (e) There are 209 affected participants with a DNA sample and at least one medical record; (f) 312 participants with at least one medical record overall; 235 medical records abstracted; (g) 7.9% of participants are NOT of European ancestry; and (h) 61% of participants completed the entire enrollment survey. Presentation: Placenta Symposium: Women Affected by Preeclampsia Taking Research into New Directions, Seattle, WA, July 7 2017.

 

Research Centre for Women’s and Infants’ Health Biobank Program May 2017 Overview (RCWIH) (Drs S Lee Adamson (Director) and Valeria Di Giovanni (Manager):

Background: The RCWIH BioBank is a cost-recovery perinatal specimen biorepository, which was developed in 2006 by, and for, researchers. We are part of the Lunenfeld-Tanenbaum Research Institute (LTRI) and the Mount Sinai Hospital (MSH)/University Health Network Department of Obstetrics and Gynaecology, in Toronto, Canada.
The BioBank specializes in the procurement, processing, and archiving of fresh, frozen and fixed specimens (human placenta and umbilical cord, umbilical cord blood, and other pregnancy-related specimens) that are suitable for a wide range of research applications. We focus on collecting specimens from healthy and pathological pregnancies, including a variety of complications such as preeclampsia, intrauterine growth restriction, preterm labour, and diabetes. We prepare in-depth clinical profiles for all specimens that are collected by our staff. Upcoming Plans: As our specimen archive grows, we are working to connect to new research and industry partners. We welcome collaboration with any CoLab members and also encourage you to share our information and website (http://biobank.lunenfeld.ca) with any interested colleagues.