How medicine safety in pregnancy is described

Assessing medicine safety during pregnancy presents a unique challenge for regulators and healthcare providers. Pregnant women experience significant physiological changes that can alter how medicines are absorbed and processed, yet they are routinely excluded from clinical trials to protect the developing fetus. Historically, regulators sought to simplify this uncertainty by assigning simple letter categories to medicines. Over time, however, it became clear that these categories were often misunderstood, leading to a global shift toward more detailed, narrative labelling that better reflects the complexities of medical risk.

The era of letter categories

In 1979, the United States Food and Drug Administration (FDA) introduced a system of five letter categories—A, B, C, D, and X—to classify the potential risks of taking medicines during pregnancy. Category A indicated that adequate human studies showed no risk, while Category X signified known risks that clearly outweighed any potential benefits. Categories B, C, and D represented varying levels of animal or human data, generally moving from insufficient evidence to demonstrated risk. Many other regulatory bodies adopted similar frameworks or relied heavily on these FDA categories.

Despite their initial appeal, the letter categories proved problematic. The system was frequently misinterpreted as a strict ranking of danger, which oversimplified the reality of medical treatment. For example, a life-saving medicine might fall into Category D because it carried some risk, while a mild, optional medicine could be in Category B. Healthcare providers and patients sometimes avoided necessary treatments simply because the letter designation sounded alarming, without considering the risks of leaving a maternal condition untreated.

The shift to narrative labelling

Recognising these limitations, the FDA replaced the letter categories with the Pregnancy and Lactation Labeling Rule (PLLR), which became fully effective in 2015. Under this system, simple letters were eliminated in favour of descriptive text. The new labels are divided into specific subsections: a risk summary, clinical considerations (such as the risks of the untreated condition to the mother and fetus), and a summary of the available data. The European Medicines Agency (EMA) similarly avoids simple categorical rankings, preferring detailed summaries of product characteristics that outline known risks and highlight gaps in data.

This narrative approach acknowledges that medicine safety in pregnancy is rarely a simple yes or no. The risk associated with a medicine often depends on the specific trimester, the dose, and the duration of treatment. By providing context, narrative labelling helps healthcare providers weigh the benefits of treating a condition against the potential risks to the fetus, facilitating more informed decisions rather than reflexive avoidance based on an arbitrary letter.

The precautionary principle and data gaps

The precautionary principle plays a central role in how medicines are studied and described for pregnant women. Because researchers cannot ethically expose a fetus to a potentially harmful substance merely to test its safety, pregnant individuals are systematically excluded from pre-marketing clinical trials. Consequently, many medicines are approved and marketed without comprehensive human pregnancy data, and safety information is often only discovered after the medicine is widely used.

When a medicine is described as having 'insufficient data' or 'unknown risk' in pregnancy, it does not necessarily mean the medicine is harmful. Rather, it means there is not enough evidence to make a definitive safety claim. Regulators rely on post-marketing surveillance, pregnancy registries, and observational studies to slowly build this evidence base over time. The precautionary principle dictates that in the absence of data, regulators will often default to caution in their labelling, but this lack of data should not be conflated with proof of harm.

Medicine labels in South Africa

In South Africa, the South African Health Products Regulatory Authority (SAHPRA) evaluates medicine safety data before granting registration. While SAHPRA does not use the FDA's retired letter categories, it requires package inserts to include detailed warnings regarding use in pregnancy and lactation based on the available global evidence. These guidelines align with international standards, ensuring that healthcare providers have access to the same narrative risk summaries used by major regulators worldwide.

For those looking to research specific medicines, the official package insert approved by the regulator is the most reliable source of safety information. Users can search for registered medicines and review their package inserts using HealthSA, where the approved, narrative safety information for pregnancy and lactation is documented.