In the 1950s and early 1960s, the medication was recommended to pregnant patients to relieve nausea. However, it resulted in over 10,000 children being born with permanent birth defects all across the world, ranging from face anomalies to limb deformities.
Evidence-based, safe, and effective medications should be available to expectant mothers. However, because to cost, risk of legal trouble, and ethical considerations, many potentially safe medications are no longer studied.
Because of this, a lot of people use drugs in ways that aren’t authorized or refuse to take the prescription pills they need because they worry that they might hurt someone.
The legacy of Thalidomide
The Thalidomide tragedy had a significant impact on current regulations and attitudes surrounding the use of medications during pregnancy.
Before it was marketed, pregnant women were not tested for thalidomide during the first trimester. We have learned a great deal from this tragic incident regarding the impact of medicines on the development of embryonic organs. It also altered the perception of pregnant women’s use of medications by the general public, the pharmaceutical industry, regulatory bodies, and ethics committees that oversee clinical trial approval.
But during the past ten years, the usage of medications during pregnancy has expanded, defying social misgivings.
According to a 2024 countrywide record involving 1.4 million pregnancies in Denmark, the proportion of pregnancies during which at least one prescription was written rose from 57% in 1998 to 63% in 2018. This is in line with a rise in the usage of certain medications (35% in 2018).
Pre-existing diseases (like asthma), incidental symptoms (like colds), and pregnancy-specific conditions (like morning sickness) are all treated with medication. Still, the majority of pregnancy use is “off-label.”
Off-label medication use during pregnancy
When a medication is prescribed for use in a manner not approved by a regulatory body, such the Australian Therapeutic Goods Administration (TGA), it is referred to as being “off-label.”
This might mean it is:
utilized for a different ailment at a different dosage given in a different manner (such as injecting into a vein as opposed to a muscle) for a patient population not covered by the approved product information.
Pregnancy-related off-label prescription is prevalent. A research conducted in the UK on nearly 18,000 inpatient prenatal medications discovered that 74% of them were used off-label, and that 55% of the manufacturers had advised against pregnancy.
What are the barriers to testing medicines during pregnancy?
Historical exclusion
Because pre-registration trials do not accept pregnant participants, off-label medication frequently happens. Therefore, even if subsequent studies demonstrate efficacy and safety in this category, they are not included in the approved usage.
Pregnant women have historically been prohibited from participating in medical trials by human research ethical committees due to the requirement that “vulnerable” individuals or women of childbearing age utilize contraception.
Still, opinions are gradually shifting. According to the World Health Organization (WHO), pregnant women should no longer be assumed to be ineligible for studies and should instead be regarded as “complex” rather than “vulnerable.”
Pregnant mothers ought to be involved in meticulously carried out studies instead. In actuality, the greatest method to guarantee their safety throughout pregnancy is to have greater knowledge about how they react to medications and their unique needs.
Rather than “protection from research,” the WHO refers to this strategy as “protection through research.”
Unwilling drug companies
In order to commercialize a new medication or modify the dosage of an already-available medication, pharmaceutical companies must apply. To prove it is safe and effective, they must submit clinical trial data to the Therapeutic Goods Administration.
There aren’t many incentives, though, for them to do studies while expecting.
Companies must take into account increased regulatory scrutiny, ethical issues, and the possibility of exposing the fetus to drugs that could disrupt its development when deciding whether to involve pregnant individuals. A lot of people are reluctant to assume the medico-legal risks.
558 industry-sponsored studies evaluating already-registered medications were audited in the US. Only five (1%) of the enrolled women were of reproductive potential, and pregnancy was expressly excluded in 95% of the procedures.
Many firms determine that evaluating a medicine’s usage during pregnancy is not commercially viable due to the associated risks and costs, particularly since pregnant women make up a small portion of the prospective user population.
Prescriber and patient concerns
Off-label prescriptions are allowed. However, if a patient gets a side effect for which the prescription is found to be the reason, the doctor who prescribed the drug for the unapproved purpose bears the legal responsibility rather than the pharmaceutical corporation.
In addition, prescribers must assess ethical and clinical considerations, balancing the need to heal with the duty of care to “first do no harm.”
More often than not, pregnant women are concerned about a medication’s safety than its efficacy. A sizable percentage overestimate the risk. When a woman becomes pregnant, this may cause her to stop taking her usual prescriptions.
It is crucial that a woman receiving an off-label prescription is properly informed of all available information, including any potential risks as well as advantages. She need to have the freedom to inquire and make her own decisions regarding the usage of the medication.
No matter how things turn out, the conversation and the patient’s informed consent—when they choose to take the medication—must be recorded.
Off-label use has become inevitable due to ongoing shortages in the supply of medications and localized discontinuations of a number of older obstetric medications, such as fast-acting oral nifedipine tablets, which lower the risk of pre-eclampsia.
Pregnant women will likely continue to be put at danger in this position until pharmaceutical companies and government regulators invest more in trials during pregnancy.
