Pregnancy is a special period in a woman’s life. Most medications taken by pregnant women can cross the placenta and enter the fetal body, thereby affecting fetal development.
The effects of medication vary depending on the stage of pregnancy:
Pre-implantation period (0-20 days): In this period, the effect of medication on the embryo is usually an all-or-nothing effect, i.e., it either leads to embryonic arrest or has no effect on the fetus.
Embryonic organogenesis period (20-56 days): This is a critical period for fetal organ differentiation, and medication can cause spontaneous abortion, major birth defects, and etc.
Late pregnancy (6-9 months): Medication is less likely to cause malformations at this time, but it can affect the normal growth and development of fetal organs.
Whether a drug can cross the placental barrier depends mainly on its physicochemical properties, such as molecular weight and plasma protein binding rate. Even if a drug cannot directly cross the placenta, it can still affect the fetus indirectly by altering placental blood flow or uterine tone.
As early as 1979, the US Food and Drug Administration (FDA) established a five-level risk classification system based on animal experiments and clinical medication experience to assess the impact on fetal teratogenicity, namely the ABCD(X) classification:
| Category | Defination |
| A | Adequate and well-controlled studies have failed to demonstrate a risk to the fetus in the first trimester and in later pregnancy. |
| B | Animal studies have not shown fetal harm, but there are no adequate human studies. |
| C | Risk cannot be ruled out, but potential benefits may outweigh risks. These medications should be used cautiously during pregnancy and only if clearly needed. |
| D | Positive evidence of risk, but potential benefits may outweigh risks in serious or life-threatening situations. These medications should only be used during pregnancy if the potential benefits outweigh the serious and potentially life-threatening risks to the developing baby. |
| X | Contraindicated in pregnancy; known to cause fetal defects. These medications should never be used during pregnancy. |
The ABCD(X) classification system has been used for decades to categorize the risks of using prescription drugs during pregnancy. However, this system has been criticized for being overly simplistic and not providing enough information to help pregnant women and their healthcare providers make informed decisions about medication use.
In 2015, the FDA implemented a new rule, the Pregnancy and Lactation Labeling Rule (PLLR), which requires drug manufacturers to provide more detailed information about the risks and benefits of using their products during pregnancy and lactation. This information must be presented in a narrative format, rather than the traditional ABCD(X) letter system.
The PLLR requires that drug labels include the following information:
A risk summary that provides an overview of the known risks of using the drug during pregnancy, including information about the potential for birth defects, miscarriage, and other adverse outcomes.
A discussion of the clinical considerations that should be taken into account when making a decision about whether or not to use the drug during pregnancy, such as the severity of the woman’s condition, the availability of alternative treatments, and the potential benefits of the drug.
Data from clinical trials and other studies that have been conducted to assess the safety and efficacy of the drug in pregnant women.
The PLLR also requires that drug labels include information about the use of the drug during lactation, including the amount of the drug that is excreted in breast milk and the potential risks to breastfed infants.
The PLLR is a significant step forward in providing pregnant women and their healthcare providers with the information they need to make informed decisions about medication use. By requiring drug manufacturers to provide more detailed and comprehensive information about the risks and benefits of their products, the PLLR can help to ensure that pregnant women receive the safest and most effective care possible.
The PLLR has been demonstrated several advantages, such as: More comprehensive information: The PLLR provides more detailed and comprehensive information about the risks and benefits of using drugs during pregnancy and lactation than the ABCD(X) classification system; Individualized decision-making: The PLLR allows pregnant women and their healthcare providers to make individualized decisions about medication use based on the specific risks and benefits of each drug; Improved safety: The PLLR can help to improve the safety of medication use during pregnancy and lactation by providing pregnant women and their healthcare providers with the information they need to make informed decisions.
The PLLR is a valuable resource for pregnant women and their healthcare providers. By providing more detailed and comprehensive information about the risks and benefits of using drugs during pregnancy and lactation, the PLLR can help to ensure that pregnant women receive the safest and most effective care possible.