Inexpensive drug prevents fatal convulsions in pregnant women, study finds
31 May 2002 - Magnesium sulfate can halve the risk of life-threatening convulsions and the risk of death in pregnant women with problems of high blood pressure, according to the findings of a major international clinical trial published in The Lancet today (Friday 31 May 2002).
The three-year study, dubbed the "Magpie" trial, was funded by the United Kingdom’s Medical Research Council (MRC), with support from the Geneva-based research programme on reproductive health (HRP) at the World Health Organization (WHO), the United Kingdom’s Department for International Development, and the European Commission’s Directorate General for Research (INCO Programme).
The trial was carried out in 33 countries and involved nearly 10 000 pregnant women with pre-eclampsia, a condition marked by high blood pressure and protein in the urine. Pre-eclampsia predisposes pregnant women to the convulsions of full-blown eclampsia. Worldwide, pre-eclampsia and eclampsia occur in about 3% of pregnant women and account for about 12% of deaths (up to 60 000 deaths) related to pregnancy. Data from the trial also showed that nearly 2% of women with pre-eclampsia go on to develop eclampsia.
"The needless death of any mother during pregnancy or childbirth is a terrible tragedy—a tragedy multiplied when she has other young children or a family dependent on her," says Dr Tomris Turmen, Executive Director of Family and Community Health at WHO. "Yet many of these deaths can be prevented. This trial proves that a very inexpensive treatment with magnesium sulfate given to every pregnant woman when she needs it can cut deaths from eclampsia by almost half," Dr Turmen said.
Up to now the only sure way of treating pre-eclampsia and preventing eclamptic convulsions has been to induce early delivery of the child. Different types of drugs—anticonvulsants, anti-epileptics, and also magnesium sulfate—have been widely used to prevent eclampsia, without conclusive scientific evidence that they are effective for this purpose.
The Magpie study settles the issue for magnesium sulfate. The 4968 women in the study who received an injection of magnesium sulfate had a 58% lower risk of eclampsia and an up to 45% lower risk of dying than the 4958 women given placebo. Side-effects were only minor: neither the mothers nor their babies have so far shown any serious adverse effects from the treatment.
Lelia Duley, an MRC senior clinical fellow and an obstetric epidemiologist at the University of Oxford, in the United Kingdom, who led the trial research team, said: "Eclampsia is a devastating condition that can kill both mother and child. Our trial has shown that giving magnesium sulfate injections could save countless lives across the world if it could be given routinely to pregnant women with pre-eclampsia. And, importantly, it is a very inexpensive treatment, making it especially suitable for use in low-income countries."
In Geneva, Paul Van Look, who heads WHO’s department of reproductive health and research, believes the findings of the Magpie trial could boost the department’s efforts, through its making pregnancy safer initiative, to reduce mortality from pregnancy-related conditions, which kill more than half a million women every year.
"At present, despite its low cost, magnesium sulfate is not a standard component of routine prenatal care in most developing countries," said Dr Van Look. "With the new evidence from the trial, our making pregnancy safer initiative has a much better chance of getting the drug more widely used throughout the world, particularly among women in developing countries, who are at greatest risk of dying as a result of their pregnancy."
Magnesium sulfate can be administered relatively simply by skilled personnel at all levels of a country’s health system. WHO includes the drug on its essential drugs list. However, only about half of the world’s countries have included it on their national lists. One reason could be that up to now evidence about the drug’s efficacy in preventing eclampsia has not been conclusive enough to prompt obstetricians to change their practising habits.
HRP senior scientist José Villar, who coordinated WHO’s participation in the Magpie trial, said that an estimated 70 000 cases of eclampsia a year could be expected in the 143 less developed countries of the world. "This means," he said, "that if we gave magnesium sulfate to all women with pre-eclampsia in these countries, we could avoid up to 35 000 cases of eclampsia every year."
Eclampsia is not the only danger a woman with pre-eclampsia faces. The Magpie trial found that 11.5% of the pregnancies in the untreated women with pre-eclampsia ended in the death of the baby at or shortly after birth. And in more than 53% of the pregnancies, the baby was born underweight (less than 2.5 Kg).
WHO is tackling this issue on two fronts. First, it is conducting a trial involving 8500 women in seven countries to find out whether giving calcium supplements to pregnant women could prevent pre-eclampsia, as some early studies have suggested it can.
Second, WHO is planning a worldwide attack on the problem through a "Global Programme to Conquer Pre-Eclampsia/Eclampsia". This proposed initiative has already enlisted the participation of research teams from Argentina, India, Mexico, South Africa, Thailand, the USA, and the United Kingdom. It will also take advantage of HRP’s worldwide research network—currently comprising 123 research centres in 59 countries—to launch large-scale multicentre studies on promising leads to preventing pre-eclampsia.
HRP is the acronym for the UNDP/UNFPA/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP), which is part of WHO’s department of reproductive health and research in the Family and Community Health Cluster.