A Stellenbosch University (SU) led team of South African and Australian researchers has achieved a milestone in the treatment of pre-term pre-eclampsia. This breakthrough has the potential to save thousands of lives caused by the fatal condition considered a dangerous complication of pregnancy.
Professor Cathy Cluver, associate professor in the department of obstetrics and gynaecology of SU’s faculty of medicine and health sciences (FMHS), led the research project, which has just been published in the British Medical Journal (BMJ).
The SU’s Health Research Ethics Committee and the South African Health Products Regulatory Authority approved the trial. The Preeclampsia Foundation, Peter Joseph Pappas research grant program and the South African Medical Research Council provided funding while Merck Healthcare contributed the trial medications but played no role in running the trial.
Causing more lives
Said Professor Cluver: “Worldwide, pre-eclampsia claims the lives of 500,000 unborn babies and 70,000 pregnant mothers every year. It is a leading cause of maternal and neonatal deaths in South Africa.” She added that the “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.”
She said 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,” said Professor Cluver.
Therapeutic candidate treatment
In the past efforts to find drugs that are safe to administer during pregnancy that could prolong gestation in preterm pre-eclampsia, have fallen short. According to Professor Cluver the idea of metformin as a treatment for pre-eclampsia came from laboratory studies done by the same research team at Mercy Hospital for Women, in Melbourne.
Professor Cluver said pre-clinical laboratory studies from the Translational Obstetrics Group in Melbourne, led by Prof Stephen Tong, recently 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-pre-eclampsia at Tygerberg Hospital, here in Cape Town” she said.
She said Tygerberg Hospital conducted a trial in which 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 3g 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,” explained Professor Cluver.
Lifelong health benefits
“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. 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,” said Professor Cluver.
She said the 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 it is inexpensive, meaning it could be widely adopted in low-and-middle income countries such as South Africa, where the problem is most pronounced. In addition, no serious side-effects related to trial medications were observed.
Larger trial to follow
The prolongation of pregnancy, said Professor Cluver, 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. Professor Cluver said 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,” she added.