Medications that cause birth defects are known as teratogens, substances that interfere with the normal development of an embryo or fetus. Determining that a specific drug causes a birth defect is complex, as congenital anomalies occur in approximately four percent of all pregnancies, even without medication exposure. The likelihood and severity of harm depend on the drug’s dose, the mother’s metabolism, and the precise timing of exposure during the pregnancy. This article provides safety information regarding certain medications and the frameworks healthcare providers use to assess risk.
The Critical Timing of Fetal Development
The risk a medication poses depends on the specific stage of fetal development. The first two weeks following conception, known as the pre-implantation period, often follow an “all-or-nothing” rule. Severe teratogenic exposure during this time will either destroy the fertilized egg, resulting in a miscarriage, or the egg will completely recover with no resulting defect.
The most sensitive period for developing major structural malformations is the embryonic period, spanning approximately three to eight weeks after conception. This is the time of organogenesis, when all major organs and body structures are rapidly forming. Exposure to a teratogen during this narrow window can cause a structural defect in the organ undergoing its most rapid development.
During the fetal period, after the eighth week, the risk of new major structural defects decreases significantly as most organs are already formed. However, later exposure can still lead to functional defects, such as growth restriction, central nervous system damage, or impaired organ function. Since the brain and spinal cord continue to develop throughout the entire pregnancy, they remain susceptible to harm from teratogens during all three trimesters.
Major Drug Classes Known to Cause Harm
A few medication classes have a high potential to cause birth defects and are generally avoided during pregnancy. The retinoids, such as isotretinoin, are highly potent teratogens known to cause severe defects involving the central nervous system, heart, and craniofacial structures. Due to this high risk, individuals must follow strict protocols, including mandatory pregnancy testing and contraception, before and during treatment.
Certain anticonvulsant medications, particularly valproate, are associated with a significantly increased risk of major congenital malformations. Exposure to valproate during the first trimester can lead to neural tube defects, like spina bifida, and other structural anomalies. Other anti-seizure medications, such as carbamazepine, have also been linked to an elevated risk of neural tube defects.
The anticoagulant drug warfarin can cause a pattern of birth defects known as Fetal Warfarin Syndrome when exposure occurs between weeks six and twelve of gestation. This syndrome is characterized by nasal hypoplasia, which is an underdeveloped nose, as well as stippled epiphyses, which are abnormal bone and cartilage formations. Later exposure can lead to central nervous system damage, including microcephaly and intellectual disabilities.
Angiotensin-Converting Enzyme (ACE) Inhibitors, a class of blood pressure medications, pose a concern primarily when taken during the second and third trimesters. Exposure during this later phase of pregnancy can impair fetal kidney function and lead to oligohydramnios, which is a low level of amniotic fluid. This reduction in fluid can result in skull malformations, lung underdevelopment, and poor fetal growth.
Chemotherapy agents are highly toxic to rapidly dividing cells, and exposure during the first trimester carries a high risk of malformation, estimated to be between 10 to 20 percent. These cytotoxic drugs interfere with the rapid cell proliferation that characterizes early organ development, often leading to growth deficiency, craniofacial anomalies, and limb malformations. The historical example of thalidomide, a drug once used for morning sickness, illustrates the potential for severe harm, causing phocomelia, a distinct malformation where limbs are severely shortened or absent.
Understanding Medication Risk Categories
The medical community previously relied on a system of five letter categories (A, B, C, D, and X) established by the FDA to communicate pregnancy risk. This older system was ultimately seen as overly simplistic and confusing because a single letter could group drugs with very different risk profiles or levels of available data. The categories also failed to convey the nuance of risk, which changes depending on the dose and timing of exposure.
The FDA has transitioned to the Pregnancy and Lactation Labeling Rule (PLR), a more comprehensive format designed to provide healthcare providers with detailed, evidence-based information. The PLR replaces the letter categories with narrative sections that offer a thorough assessment of the medication’s effects. The new rule requires manufacturers to include three distinct sections in drug labeling:
- Pregnancy
- Lactation
- Females and Males of Reproductive Potential
The Pregnancy section is broken down further into a Risk Summary, Clinical Considerations, and Data, which summarize human and animal data and provide guidance on dose adjustments. This framework helps a provider weigh the potential risks of the medication against the dangers of an untreated underlying maternal illness.
Consulting Healthcare Providers Regarding Medication Use
Pre-conception planning is the safest and most proactive step an individual can take to manage medication risk before pregnancy begins. Individuals planning to become pregnant should schedule a comprehensive review of all prescription drugs, over-the-counter medicines, and supplements with their healthcare provider. This review allows for the safe substitution of potentially harmful medications with safer alternatives or adjustments to the current dosage regimen.
If a pregnancy is discovered while taking a prescribed medication, it is extremely important not to stop the treatment abruptly without consulting a doctor. The risk to the fetus from an untreated or poorly controlled maternal condition, such as epilepsy, depression, or severe asthma, can often be greater than the potential risk posed by the medication itself. A healthcare provider can help balance these risks, determining the least hazardous medication and the lowest effective dose.
For some medications, specific patient registries exist to collect data from individuals who have been exposed to a drug during pregnancy. These pregnancy exposure registries are observational studies that monitor outcomes and gather systematic, human-specific safety information that is otherwise difficult to obtain. Enrolling in a registry, when available, helps researchers and providers better understand the medication’s true effects, which ultimately contributes to improved counseling and care for future pregnancies.