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Stellenbosch doctor leads breakthrough research to combat pre-eclampsia, a deadly pregnancy complication
Author: FMHS Marketing & Communications / FGGW Bemarking & Kommunikasie – Ilse Bigalke
Published: 23/09/2021

​A potentially life-saving breakthrough in the treatment of preterm pre-eclampsia, a dangerous complication of pregnancy, has been achieved by a Stellenbosch University-led team of South African and Australian researchers.

The exciting findings of this study, led by Prof Cathy Cluver, Associate Professor in the Department of Obstetrics and Gynaecology of SU's Faculty of Medicine and Health Sciences (FMHS), have just been published in the British Medical Journal (BMJ).

“Worldwide, pre-eclampsia claims the lives of 500,000 unborn babies and 70,000 pregnant mothers every year. It is a leading causes of maternal and neonatal deaths in South Africa" says Cluver. “Pre-eclampsia that develops at an early gestation, called preterm pre-eclampsia, is a highly dangerous variant of the disease where the risks to baby and mother are particularly high"

According to Cluver the only existing treatment for pre-eclampsia is to deliver the baby and placenta. “Late in a pregnancy it is fairly safe to deliver a baby, but if delivery is preterm, it can result in severe complications associated with prematurity and could even result in death of the baby."

Previous efforts to find drugs that are safe to administer during pregnancy that could prolong gestation in preterm pre-eclampsia, have not succeeded. The idea of metformin as a treatment for preeclampsia came from laboratory studies done by the same research team at Mercy Hospital for Women, in Melbourne.

 “Recently, preclinical laboratory studies from the Translational Obstetrics Group in Melbourne, led by Prof Stephen Tong, identified metformin as a therapeutic candidate for pre-eclampsia. We then set out to evaluate whether oral metformin could prolong gestation among women diagnosed with preterm-preeclampsia at Tygerberg Hospital, here in Cape Town" says Cluver.

In this trial, conducted at Tygerberg Hospital, the researchers recruited 180 women with preterm pre-eclampsia between 26 and 32 weeks gestation. The women were recruited between February 2018 and March 2020. “The mothers needed to be stable enough to undergo inpatient expectant management for preterm pre-eclampsia. Half of them received 3 g of oral metformin daily, while the other 90 were given dummy tablets (placebo). None of the participants or researchers knew who was taking the active drug until the trial was completed".

“What is really exciting is that the women who took metformin stayed pregnant for 7,6 days longer compared to those who took a placebo. A full week. Furthermore, their babies spent 12 days less in hospital. When we are dealing with this level of prematurity, an extra week in the mother's womb is likely to be a really important gain that could translate in lifelong health benefits for the baby."

“It is the first time that a treatment given to mums with preterm pre-eclampsia to keep them pregnant for a week longer might have worked," explains a delighted Cluver. “It could mean that preterm pre-eclampsia can now be treated and that we can slow disease progression right down."

Advantages of metformin include that it is already widely used to treat gestational diabetes, and it is therefore likely to be safe, especially if administered for a limited duration. A further advantage is that metformin is inexpensive, meaning it could be widely adopted in low-and-middle income countries (LMIC's) such as South Africa, where the problem is most pronounced. Also, no serious side-effects related to trial medications were observed.

Cluver adds that the prolongation of pregnancy among the participants may have been longer had they continued with the treatment beyond 34 weeks gestation. However, the babies of women with preterm pre-eclampsia managed at Tygerberg Hospital are delivered at 34 weeks.

According to her the next step is a larger trial, involving 500 participants, to confirm the findings. “If the findings are confirmed, it means that metformin could be used to save the lives of thousands of mothers and their infants."

*The trial was approved by SU's Health Research Ethics Committee and the South African Health Products Regulatory Authority.

Funders were: The Preeclampsia Foundation, Peter Joseph Pappas research grant program and the South African Medical Research Council. Merck Healthcare kindly provided the trial medications but played no role in running the trial.