Pressure Grows to Include Pregnant Women in Trials

The lack of accurate and extensive data about the safety and effectiveness of a wide range of drugs in pregnancy has restricted the treatment of pregnant women and contributed to an underlying health problem over the past 20 years, according to an editorial published in the June issue of Drug and Therapeutics Bulletin (DTB).

“Pregnancy is a natural state that has been ignored by the pharmaceutical industry for too long,” noted the editors of DTB. “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 involved pregnant women rather than automatically exclude them.” [Prescribing in pregnancy—therapeutic discrimination? DTB Vol 51;6:June 2013]

In the absence of reliable information about the pros and cons of treatment during pregnancy, and haunted by the specter of thalidomide, many doctors are reluctant to prescribe medication, the authors stated. Also, pregnant women often are wary of taking drugs that might harm their fetus, even though an estimated one in 10 mothers-to-be has a long-term condition that requires medication and around four out of 10 develop new health problems during their pregnancy.

Furthermore, the situation is going to get worse because of the increasing trend toward having children later in life and the rise of obesity, both of which are pushing up the numbers of women requiring drug treatment during their pregnancy, warns the editorial. In England and Wales in 2011, for instance, around 4% of women who gave birth were aged 40 and over—compared with just 1% a decade earlier—while almost one in five women of childbearing age were obese in 2008.

The unwillingness to prescribe and be treated can be fatal, warns the DTB editorial. For example, the number of “indirect” deaths among new mothers in the U.K. has almost doubled over the past two decades, and it now exceeds deaths directly caused by pregnancy by 50%.

It is rare for a drug company or research team to include pregnant women in drug trials, according to the authors. All too often they are put off by the difficult logistical and other challenges involved, but it is the time to emulate the way in which children’s medicines are now being investigated properly, they argue, and it calls on industry and regulators to include more women in clinical trials.

“Although there are complex ethical issues associated with studying drugs in pregnant women, some researchers argue that it is unethical not to obtain dosing information for drugs that are frequently used by pregnant women,” the authors wrote. “However, in the absence of robust trials, adverse effects can take many years to become apparent: sodium valproate 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.”

Greater input is needed from the pharmaceutical industry and health regulatory bodies, with greater emphasis on research, registry data collection, wider availability of information, increased integration of information sources and the development of shared-decision aids for patients and healthcare professionals, the editorial concluded.

For further reading on this topic, the DTB suggests the following sources:

• Goldkind SF et al. Enrolling pregnant women in research—lessons from the H1N1 influenza pandemic. N Engl J Med 2010; 362: 2241-3.

• European Medicines Agency, 2013. Paediatric regulation [online]. Available: http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/document_ listing/document_listing_000068.jsp.