Pregnant individuals face a unique set of health challenges, from managing pre-existing conditions to dealing with pregnancy-specific issues such as nausea or morning sickness. Unfortunately, despite the need for safe, effective, and evidence-based medication, getting drugs approved for use during pregnancy remains a complex and difficult process. The reasons for this range from ethical concerns to financial disincentives, which leaves pregnant women and their healthcare providers in a challenging position.
In this blog, we will explore the barriers to testing and approving medications for pregnancy, the legacy of past medical failures, and the realities of “off-label” drug use during pregnancy.
The Legacy of Thalidomide: A Cautionary Tale
One of the most significant events that shaped the way medications are tested and used during pregnancy is the Thalidomide disaster. In the 1950s and early 1960s, Thalidomide was prescribed to pregnant women to treat morning sickness. Tragically, it led to over 10,000 children worldwide being born with severe birth defects, including limb deformities and facial malformations.
Thalidomide was never tested on pregnant women before it was marketed, which taught the medical community valuable lessons about how drugs can affect fetal development. This incident dramatically shifted the perspective of pharmaceutical companies, regulators, and the public when it comes to drug use during pregnancy.
Increased Medication Use in Pregnancy
Despite the societal fears following the Thalidomide incident, the use of medications during pregnancy has actually increased over the last decade. A 2024 study from Denmark, which examined 1.4 million pregnancies, found that 63% of pregnant women were prescribed at least one medication in 2018, up from 57% in 1998. This increase is driven by the need to manage pregnancy-specific conditions (like nausea), incidental symptoms (like colds), and pre-existing medical conditions such as asthma.
However, the majority of these medications are prescribed “off-label,” meaning they haven’t been specifically approved for use during pregnancy.
What Is Off-Label Medication Use?
Off-label medication use refers to the practice of prescribing a drug in a way that hasn’t been approved by regulatory authorities. This could involve:
- Using the drug for a different medical condition than what it was approved for.
- Administering the drug in a different dosage or format.
- Prescribing it to a patient group not included in the official guidelines (like pregnant women).
One study in the UK found that 74% of medications prescribed during pregnancy were off-label, with 55% of them carrying manufacturer warnings against use during pregnancy.
Why Are Drugs Rarely Tested During Pregnancy?
There are several reasons why drug testing during pregnancy is rare:
1. Historical Exclusion of Pregnant Women in Trials
Historically, pregnant women have been excluded from clinical trials, partly due to the ethical concerns about exposing a fetus to potentially harmful substances. Human research ethics committees often classified pregnant women as “vulnerable” participants, further limiting their inclusion in drug trials.
However, attitudes are beginning to change. The World Health Organization (WHO) now recommends viewing pregnant women as “complex” rather than “vulnerable,” meaning they should not automatically be excluded from trials. Instead, they should be included in carefully conducted research that considers both their needs and the needs of the developing fetus.
2. Lack of Incentive for Drug Companies
Pharmaceutical companies are often unwilling to conduct drug trials on pregnant women because of the potential risks and legal liabilities involved. If something were to go wrong, the financial and reputational damage could be severe. Additionally, pregnant women represent a relatively small market segment, making the financial return on investment less appealing.
A U.S. study of 558 industry-sponsored drug trials found that only 1% included women of childbearing potential. The cost, ethical concerns, and legal risks make it unlikely that drug companies will take the initiative to conduct pregnancy-specific trials without external incentives.
3. Legal and Ethical Concerns for Prescribers
Even though off-label prescribing is legal, it places a significant burden on healthcare providers. If a patient experiences an adverse outcome from an off-label medication, the legal responsibility often falls on the prescribing doctor rather than the pharmaceutical company.
Doctors must balance the ethical obligation to “first do no harm” with the need to provide effective treatment. For pregnant women, the focus is often on safety rather than efficacy, which can lead to an overestimation of the risks associated with taking medication during pregnancy. This may cause some women to avoid essential treatments, potentially compromising their health and the health of their baby.
The Role of Informed Consent
When prescribing off-label medications during pregnancy, it is crucial that healthcare providers fully inform the patient about the risks and benefits of the drug. Pregnant women should have the opportunity to ask questions and decide whether they want to proceed with the treatment. This process, known as informed consent, must be thoroughly documented.
Conclusion: A Call for Greater Research and Investment
Without more investment from both pharmaceutical companies and government regulators, the issue of off-label prescribing during pregnancy is unlikely to change. Pregnant women need safe and effective medications, but without rigorous testing and approval processes, healthcare providers are left with limited, often imperfect, options.
In the meantime, the inclusion of pregnant women in clinical research, with the necessary ethical safeguards, is a step in the right direction. This approach, termed “protection through research” by the WHO, emphasizes the importance of understanding how medications work in pregnancy rather than excluding pregnant women from research altogether.