The thalidomide tragedy of the late 1950s and early 1960s left more than 10,000 offspring of women exposed to the drug in early first trimester with irreversible congenital defects ranging from limb deformities (phocomelia) to facial malformations. It was also implicated in thousands of spontaneous abortions.
This taught us important lessons about how drugs can impact on fetal organ development.
However, the thalidomide tragedy changed how medicines are viewed during pregnancy – not only by pregnant women, but also the wider community.
Why do women take medicines during pregnancy?
An analysis of nearly 5,000 pregnancy-related questions from Australian consumers shows women are concerned about safe drug use in pregnancy. They are also likely to overestimate the risks.
Despite their fears, pregnant women commonly need to use medication during the nine months of gestation. A recent study found 81.2% of women in Europe, North America, South America and Australia reported using at least one prescribed or over-the-counter medication during pregnancy.
This should not be surprising. If planning a pregnancy, women should already be taking folate supplements (to reduce the risk of neural tube defects) and iodine supplements (to support the fetus’ developing brain and nervous system).
They may need to continue taking medication for any underlying medical condition, or require therapy for a pregnancy-associated medical condition, such as morning sickness.
They are also likely to require symptom relief for an episodic illness such as headache or pain.
Excluding pregnant women from drug trials
For more than half a century, health professionals were taught that pregnant women were “vulnerable” participants of research who, for ethical reasons, should either be excluded from drug trials or be required to use contraception while taking part.
But excluding pregnant women from clinical trials has made them “therapeutic orphans”, forced to use medication “off-label”. This means the drug hasn’t been tested for safety and efficacy in pregnancy and regulators haven’t officially approved this use.
We have therefore done little to prevent another thalidomide tragedy.
Attitudes are, however, changing. In November 2015, the American College of Obstetricians and Gynecologists (ACOG) radically updated its 2007 position statement on research involving women. The college called for “evidence-based consideration of pregnancy exposures in research rather than broad exclusion of all pregnant women”.
The statement acknowledges that pregnant women are complex, rather than vulnerable, participants who can make autonomous decisions about whether to participate in research.
The college concludes that although there is concern that including pregnant women in drug trials could cause harm to the fetus, excluding these women from research can also lead to harm:
The pursuit of zero fetal risk is not attainable and will come at a real risk to maternal health, and potentially to the health of a wider population of fetuses, outside the research setting.
Overestimating the risks
Medication-induced birth defects tend to be overestimated by the public. This prompts some women to stop taking medication for ongoing health conditions when they become pregnant.
However, failing to treat conditions such as epilepsy or depression can be a greater risk to both mother and fetus. All couples have a 3-5% “background risk” of having a baby with a major birth defect. Untreated maternal disease, such as epilepsy or depression, can actually increase this background risk.
Some drugs have been unfairly crucified in response to the thalidomide saga. It took a meta-analysis of 170,000 safe exposures to the morning sickness drug Bendectin (a combination of doxylamine-dicyclomine and vitamin B6), before the product was finally reintroduced, with US Food and Drug Administration (FDA) approval, in 2013.
Bendectin was originally marketed in the mid-1950s for nausea and vomiting of pregnancy, but was voluntarily withdrawn in 1983 as the manufacturer found the cost of defending the drug prohibitive.
What should you do?
Some medications must be absolutely avoided during pregnancy. This includes thalidomide, vitamin A derivatives, certain anticancer and immune-modifying medicines, high doses of alcohol, the epilepsy drug phenytoin, the anticoagulant warfarin, the mood stabilisers valproate and lithium (to treat bipolar disorder).
For other drugs, the first step is to decide if the medicine is needed or not. If it is, look for a Category A medicine on the Australian Categorisation System for Prescribing Medicines in Pregnancy, or your national classification system. Category A means large numbers of women have taken the drug without adverse affects to them or their unborn babies.
By reading the packaging, labels and information that come with a medicine, and asking questions of your health providers, you can get the right advice to use medication safely in pregnancy.