More drug studies need to include pregnant women, says bulletin

BMJ 2013; 346 doi: (Published 14 June 2013) Cite this as: BMJ 2013;346:f3812
  1. Zosia Kmietowicz
  1. 1BMJ

Doctors too often say “no” or “don’t know” to pregnant women who ask whether they can take certain drugs when pregnant because of a lack of evidence on the drugs’ safety and effectiveness, an editorial in the Drug and Therapeutics Bulletin has said.1

The number of “indirect” deaths of new mothers in the United Kingdom—where pregnancy worsens a new or pre-existing medical or mental health problem—has almost doubled over the past 20 years and now exceeds the number of deaths directly caused by pregnancy by 50%, it said. The figures show that in 1985-7 there were 139 direct deaths (6.1 per 100 000 pregnancies) and 84 indirect deaths (3.7 per 100 000). By 2006-8 the number of direct deaths had fallen to 107 (4.6 per 100 000) while indirect deaths had risen to 154 (6.7 per 100 000).2 The leading causes of death are cardiac conditions, neurological disorders, sepsis, thromboembolism, and mental health problems.

More drug trials should include pregnant women to make up the knowledge gap, said the bulletin.

Doctors are reluctant to prescribe drugs for pregnant women, and pregnant women are wary of taking them, largely because of the repercussions of the thalidomide scandal in the late 1950s and early 1960s. Yet an estimated one in 10 pregnant women has a long term condition that requires drug treatment, while around four in 10 develop new health problems during their pregnancy.

About 4% of women who gave birth in England and Wales in 2011 were aged 40 or over—up from just 1% a decade earlier—and in 2008 almost a fifth of women of childbearing age were obese. These proportions were likely to increase as the average age of pregnant women and the prevalence of obesity rose, pushing up the numbers of women needing drug treatment during pregnancy, the editorial warned.

It was rare for a drug company or research team to include pregnant women in drug trials, it said, often because researchers were put off by the complex ethical issues involved. However, it could be argued that it was not ethical to exclude pregnant women from drug trials, especially as side effects could take many years to emerge.

The bulletin cited the antiepileptic drug sodium valproate as a case in point. It noted that the drug was “hailed as a wonder anticonvulsant in the 1960s, linked with neural tube defects in the 1980s, and associated with adverse neurodevelopmental effects in the offspring with third trimester exposure in the 2000s.”

The way in which drugs for children were now being investigated properly should be emulated for drugs for pregnant women, said the editorial, and it called on the drug industry and regulators to act.

“With increasing awareness that the intrauterine environment is important for the long term development of children, it is ever more important that those involved in drug development and trials look for ways to safely involve pregnant women rather than automatically exclude them,” said the editorial.

“Pregnancy is a natural state that has been ignored by the pharmaceutical industry for too long.”


Cite this as: BMJ 2013;346:f3812


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