Gynuity Health Projects



Preeclampsia and eclampsia are serious conditions unique to pregnancy and the postpartum period, most often characterized by a rapid rise in blood pressure. If not diagnosed and treated promptly they can lead to seizure, stroke, organ failure, and death of the mother and/or fetus. Affecting 5-8% of pregnancies, preeclampsia is a leading cause of maternal and fetal death, resulting in approximately 60,000 maternal deaths worldwide each year [1]. Fetal deaths are three times more frequent in women with preeclampsia and four times more frequent in women with eclampsia [2]. Gynuity’s goal is to increase access to evidence-based screening, prevention, and treatment for preeclampsia and eclampsia, especially in low-resource settings, and in so doing, reduce maternal and infant mortality and improve the quality of care available to all women.

Screening for preeclampsia
The diagnosis of preeclampsia has traditionally relied on the presence of hypertension and proteinuria. Unfortunately, these signs are often non-specific and could be confounded with essential hypertension and chronic kidney disease. Researchers have identified that women with severe forms of preeclampsia excrete high amounts of unfolded or misfolded proteins in their urine. This phenomenon classifies preeclampsia as a protein conformational disorder. (Creutzfeldt–Jakob disease, Alzheimer’s disease, and Parkinson’s disease are also characterized by such proteins.) Misfolded proteins in preeclampsia urine exhibit congophilia or affinity for Congo Red dye, originally developed for the textile industry in the 1800’s. Based on the information that Congo Red was found to stain selectively misfolded protein in brains of Alzheimer’s patients, colleagues at Nationwide Children’s Hospital in Ohio developed a simple urine diagnostic test [Congo Red Dot (CRD) Test]. With the CRD developers and hospitals in Mexico and Bangladesh, Gynuity is testing the clinical utility and usability of the CRD for the diagnosis and prediction of preeclampsia during pregnancy and in the postpartum period.

Increasing Access to Magnesium Sulfate
Magnesium sulfate, an inexpensive drug, is an effective treatment for preeclampsia and eclampsia, but it is used sub-optimally in many settings. In general, a loading dose of magnesium sulfate is administered intravenously and intramuscularly followed by an intramuscular (IM) injection every four hours or by a continuous intravenous (IV) infusion. Although the IV regimen has been shown to be effective, it requires the use of an infusion pump for safe delivery and, when administered manually, has a greater potential for inadvertent overdose and missed or delayed administration. The IM dosing regimen, while potentially safer, requires painful injections and is often initiated only when delivery is imminent. These limitations in administration may result in delayed or inadequate treatment of preeclamptic women.

The Springfusor® pump offers an alternative to intramuscular administration of magnesium sulfate where electronic pumps for IV administration are not available. Introduction of the Springfusor® has the potential to improve the quality of preeclampsia care by making drug administration easier and more acceptable to women and providers. The Springfusor® may help avoid the barriers associated with IM administration and the dangers of “free running” IV magnesium sulfate. Gynuity is studying the use of the Springfusor®, hypothesizing that it could offer a treatment approach that is superior to the current standard of care in terms of accurate delivery of treatment, ease of use, cost-effectiveness, demands on staff time, reduction of pain and side effects in women receiving the treatment, and increased acceptability to patients.

Improving Management of Hypertension in Pregnancy
Treatment of elevated blood pressure—one of the primary signs of preeclampsia—reduces the risk for maternal complications such as cerebral hemorrhage and cerebral edema. Clinical trial regimens for the acute treatment of high blood pressure generally use medications administered intravenously (e.g. hydralazine, labetalol). While these regimens are effective, they present certain challenges in low-resource settings. IV regimens require venous access, thus a provider trained in IV administration is necessary. In addition, IV regimens may reduce blood pressure too rapidly, potentially destabilizing maternal hemodynamics at the expense of the fetus, and thus careful fetal monitoring is required.

To determine the effectiveness of an alternative oral medication regimen, Gynuity, in collaboration with colleagues at the University of British Columbia, the University of Washington, Government Medical College (GMC) and Daga Memorial Women’s in Nagpur, India, is conducting a study to compare the efficacy of oral labetalol, oral nifedipine and oral methyldopa for management of severe hypertension in pregnant women. Evidence of the relative risks and benefits of different oral regimens will help develop guidance for antihypertensive use in pregnancy.

Improving Care at Delivery for Women with Preeclampsia
While magnesium sulfate and various anti-hypertensive therapies can reduce the morbidity associated with preeclampsia, the only cure comes with delivery. Prompt delivery, preferably by vaginal route, is vital in order to achieve good maternal and neonatal outcomes when preeclampsia is present. Induction of labor is therefore a critical intervention in order to prevent morbidity to both mother and baby. Two low-cost interventions—oral misoprostol tablets and transcervical Foley catheterization—are already used in some low-resource settings for labor induction, but their relative risks and benefits are unknown. Gynuity is collaborating with the University of Liverpool and Government Medical College Nagpur on a randomized controlled trial to compare these two methods of labor induction. The results of the trial will provide insight into the benefits and trade-offs in efficacy, safety, acceptability and cost of the two methods. Such information will be useful for the development of clinical guidelines and recommendations both in low-resource settings.

Consortium and working groups

Gynuity is a member of the PRE-EMPT (PRE-eclampsia & Eclampsia Monitoring, Prevention & Treatment) research group. Led by the University of British Columbia, with funding from the Bill & Melinda Gates Foundation, the theme of PRE-EMPT is to develop, test and introduce new knowledge that will reduce the unacceptable maternal, perinatal, family, societal, and global impacts of pre-eclampsia, and the other hypertensive disorders of pregnancy. The PRE-EMPT initiative consists of five inter-related objectives to be conducted over a seven year period (Nov 2010 – Oct 2017): Prevention, Monitoring, Treatment, Global Pregnancy CoLaboratory, and Knowledge Translation. Over 40 institutions and organizations around the world are involved with PRE-EMPT.

Gynuity also participates in the global coalition “Ending Eclampsia”. This project, led by the Population Council, builds on Population Council research and interventions in Bangladesh, Mexico, and Nigeria since 2007 to improve the availability and correct use of magnesium sulfate in maternal health care settings. Ending Eclampsia, in collaboration with national obstetrician/gynecologist and midwifery societies, is working to expand program activities to Ethiopia and Pakistan.

[1] Say L, Chou D, Gemmill A, Tunçalp Ö, Moller AB, Daniels J, Gülmezoglu AM, Temmerman M, Alkema L. Global causes of maternal death: a WHO systematic analysis. Lancet Glob Health. 2014 Jun;2(6):e323-33.
[2] Abalos E, Cuesta C, Carroli G, Qureshi Z, Widmer M, Vogel JP, Souza JP; WHO Multicountry Survey on Maternal and Newborn Health Research Network. Pre-eclampsia, eclampsia and adverse maternal and perinatal outcomes: a secondary analysis of the World Health Organization Multicountry Survey on Maternal and Newborn Health. BJOG. 2014 Mar;121 Suppl 1:14-24.