Preeclampsia and eclampsia are serious conditions unique to pregnancy and the postpartum period, most often characterized by a rapid rise in blood pressure. 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. Fetal deaths are three times more frequent in women with preeclampsia and four times more frequent in women with eclampsia.
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 death and improve the quality of care available to all women.
Screening for Preeclampsia
The diagnosis of preeclampsia has traditionally relied on the presence of raised blood pressure (hypertension) and excess protein in urine (proteinuria). In certain settings, the equipment to diagnose these indicators can be unreliable or there is a lack of trained personnel to use the standard diagnostics. Research has shown that women with severe forms of preeclampsia excrete in their urine unfolded or misfolded proteins, which bind to Congo Red dye (“congophilia”). The affinity of misfolded proteins for Congo Red led a hospital in the US to develop the Congo Red Dot (CRD) Test, a simple paper-based urine diagnostic test that can be used at the bedside or in outpatient settings.
With the CRD developers and hospitals in Mexico and Bangladesh, Gynuity evaluated the clinical utility and usability of the CRD test for the diagnosis and prediction of preeclampsia during pregnancy and in the postpartum period. Results from this prospective, case-control study suggest that urine congophilia can be rapidly identified and that a point-of-care diagnostic for detection of urine congophilia has the potential to improve the triage and diagnosis of patients with preeclampsia. Consult related resource here (2020).
Improving Management of Hypertension in Pregnancy
Treatment of elevated blood pressure—one of the primary signs of preeclampsia—reduces the risk for maternal complications. Historically, regimens for the acute treatment of high blood pressure used medications administered intravenously, which require venous access and monitoring of the fetus. Oral anti-hypertensive medications are easy to use, widely available and inexpensive, and can be used in a wider range of settings.
Together with the University of British Columbia, the University of Washington, Government Medical College (GMC) and Daga Memorial Women’s Hospital in Nagpur, India, Gynuity conducted a randomized trial to compare the efficacy of three oral anti-hypertensive drugs: labetalol, nifedipine and methyldopa. The study found that oral anti-hypertensives are effective in controlling severe hypertension in pregnancy without serious maternal or fetal complications. Use of oral anti-hypertensive drugs for treatment of severe hypertension in pregnancy represents an innovative approach with the potential to increase access to life-saving care at the lowest levels of the health system. Consult related resource published in The Lancet here (2019).
With funding from the Innovation Fund of the Reproductive Health Supplies Coalition, Gynuity conducted a landscape assessment of access to essential supplies for treatment of hypertensive disorders of pregnancy in Uganda, Mexico and India. In all three countries, challenges were identified on both the supply and demand sides in relation to the availability of good quality blood pressure devices and antihypertensive medications, which were the key supplies assessed in this analysis.
Improving Care at Delivery for Women with Preeclampsia
Prompt delivery, preferably by vaginal route, is a critical intervention for women with preeclampsia in order to prevent morbidity to the mother and baby. Together with the University of Liverpool and GMC Nagpur (India), Gynuity studied the relative risks and benefits of low-cost methods for labor induction (misoprostol and Foley catheterization) and augmentation (misoprostol and oxytocin) in women with preeclampsia.
The findings from the first study showed that oral misoprostol is more effective than transcervical Foley catheterization for the induction of labor. Enrollment was completed for a second study performed at three hospitals in India to assess whether oxytocin augmentation following misoprostol can be replaced by regular doses of oral misoprostol tablets. In many lower-income countries, electronic infusion pumps are not available and oxytocin has to be administered through a gravity pump. These infusions have potential for human error and require constant supervision from experienced staff. It is essential to understand how maternity care can be improved and offered more efficiently.
Increasing Access to Magnesium Sulfate
Magnesium sulfate is an inexpensive medication used to reduce the risk of seizures in women with preeclampsia, but it is used sub-optimally in many settings. In general, a loading dose of magnesium sulfate is administered intravenously and intramuscularly, followed by continuous intravenous (IV) infusion or regular intramuscular (IM) injections. Although the IV regimen is 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.
The Springfusor® is a simple, mechanically flow-controlled pump that offers an alternative to IM magnesium sulfate where electronic pumps for IV administration are not available. A study by Gynuity and partners comparing the use of the Springfusor® for the delivery of magnesium sulfate with the standard of care found that the Springfusor® pump was superior in terms of accurate delivery of treatment, ease of use, demands on staff time, reduction of pain and side effects, and increased acceptability to patients.
A more recent study implemented in two hospitals in Egypt concluded that serial IV boluses achieve serum magnesium concentrations that are significantly higher but clinically comparable to those achieved with a continuous infusion and offer a third option for the administration of magnesium sulfate.
Partnerships for Policy and Practice
Partnerships for Policy and Practice
PRE-EMPT (PRE-eclampsia & Eclampsia Monitoring, Prevention & Treatment) research group
Gynuity was 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 was 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 consisted 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 were involved with PRE-EMPT.
Ending Eclampsia Project
Gynuity participated in the global coalition “Ending Eclampsia”. This project, led by the Population Council, built 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, worked to expand program activities to Ethiopia and Pakistan.
Reproductive Health Supplies Coalition
Gynuity served as the co-chair of the hypertension sub-group in the maternal health caucus of the RHSC.
- The Induction With Foley OR Misoprostol (INFORM) Study Dataset. A Dataset of 602 Women With Hypertensive Disease in Pregnancy, in India, Randomised to Either Foley Catheter or Oral Misoprostol for Induction of Labour
- Oral Misoprostol Alone versus Oral Misoprostol Followed by Oxytocin for Labour Induction in Women with Hypertension in Pregnancy (MOLI): Protocol for a Randomised Controlled Trial
- Congo Red Test for Identification of Preeclampsia: Results of a Prospective Diagnostic Case-Control Study in Bangladesh and Mexico
- Landscape Assessment of Antihypertensive Medicines and Blood Pressure Devices in Three Countries
- GHP Study Protocol No. 4000 Oral Antihypertensive Regimens for Management of Severe Hypertension in Pregnancy
- Oral Antihypertensive Regimens for Management of Severe Hypertension in Pregnancy
- A Randomized Trial Comparing the Pharmacology of Magnesium Sulfate When Used to Treat Severe Preeclampsia With Serial Intravenous Boluses Versus a Continuous Intravenous Infusion
- Preeclampsia Program Brief
- Foley Catheterisation versus Oral Misoprostol for Induction of Labour in Hypertensive Women in India (INFORM): A Multicentre, Open-Label, Randomised Controlled Trial
- Induction of Labour in Pre-eclamptic Women: A Randomised Trial Comparing the Foley Balloon Catheter with Oral Misoprostol
- Preeclampsia in Low and Middle Income Countries-Health Services Lessons Learned From the PRE-EMPT (PRE-Eclampsia-Eclampsia Monitoring, Prevention and Treatment) Project
- Magnesium Sulphate for Prevention of Eclampsia: Are Intramuscular and Intravenous Regimens Equivalent? A Population Pharmacokinetic Study
- Treatment Approaches for Preeclampsia in Low-Resource Settings: A Randomized Trial of the Springfusor Pump for Delivery of Magnesium Sulfate
- Facility and Personnel Factors Influencing Magnesium Sulfate Use for Eclampsia and Pre-Eclampsia in 3 Indian Hospitals