Before the mid-20th century, it was generally believed that the placenta served as a natural barrier, preventing medications taken by pregnant women from affecting the fetus. However, in the 1950s, the emergence of the thalidomide disaster (which caused fetal limb defects) led to the enactment of the United States Drug Amendments of 1962. According to this regulation, drug labels must include information regarding safety, efficacy, indications for use, and related research findings.
Since the fetus is in a developmental stage with incomplete organ formation, medications taken by pregnant women may directly or indirectly affect the fetus. Most medications can cross the placenta and act directly on the fetus, requiring extreme caution when prescribing or using medications during pregnancy. Improper medication use by pregnant women can adversely impact not only maternal health but also the fetus and neonate. Therefore, minimizing the use of medications during pregnancy is emphasized, with clinical practice adhering to the principle that "medications should not be used during pregnancy unless absolutely necessary," particularly in the first trimester.
Women of childbearing age planning to conceive are advised to exercise caution when using medications. Additionally, maternal health is essential for normal fetal growth and development; those with acute or chronic illnesses should seek treatment before conception. If a pregnant woman has already taken a potentially teratogenic medication, the assessment of harm should consider the type of medication, the gestational age at the time of use, duration of exposure, and dosage. Based on these factors, counseling recommendations should be provided. When counseling pregnant or lactating women about medication exposure or selecting appropriate medications, evidence from animal studies and human trials should be reviewed.
##Basic Principles of Medication Use During Pregnancy
The following principles guide medication use during pregnancy:
- Medications should be used only with clear and defined indications to avoid unnecessary use.
- Medications that are effective for the condition and relatively safe for the fetus should be selected under the guidance of a physician.
- Single medications are preferred, and combinations of drugs should be avoided.
- Medications with well-established safety profiles are recommended, and newer drugs with undefined effects on the fetus should be avoided.
- Dosage and duration of treatment must be carefully controlled, and medications should be discontinued promptly when possible.
- If the clinical condition allows, medication use during early pregnancy should be deferred to the second or third trimester.
Classification of Medications During Pregnancy
The U.S. Food and Drug Administration (FDA) categorizes medications into five groups based on their teratogenic risks to animals and humans:
- Category A: Clinical studies have not demonstrated harm to the fetus during the first, second, or third trimesters, with extremely low risk.
- Category B: Limited or inconclusive evidence of harm to the fetus in clinical studies conducted during any trimester.
- Category C: Animal studies have shown that the medication causes fetal malformations or death, but human studies are not available. Use requires a cautious assessment of the medication's potential effects on the fetus.
- Category D: Evidence exists of harm to the human fetus, but the medication may be used for critical conditions where no alternative drugs are available. The risks and benefits must be carefully evaluated.
- Category X: Clear teratogenic effects demonstrated in both animals and humans. These medications are strictly contraindicated during pregnancy.
This classification method has limitations. Only 40% of medications are included in the FDA's pregnancy categorization, with over 60% classified as Category C. This implies that harm cannot be ruled out, requiring the weighing of potential benefits against risks. Additionally, the classification system does not provide evidence of fetal harm during different stages of pregnancy or address the effects of varying dosages. As a result, the classification system alone can be overly general, complicating medication counseling.
In 2008, the FDA proposed replacing the previous classification system with a more detailed and informed approach comprising the following components:
- Fetal Risk Summary: This section details the effects of the medication on the fetus and specifies whether the data is derived from animal studies or human trials.
- Clinical Considerations: This section includes the impact of the drug, especially in women unaware of their pregnancy at the time of use, along with information on dosage and potential complications.
- Data Section: A more detailed presentation of relevant data from animal or human studies, serving as the evidence basis for the "Fetal Risk Summary."
Gestational Timing and Medication Use
The timing of medication use during pregnancy is closely related to the nature of potential harm:
Within Two Weeks of Fertilization
The effects of medication on the embryo follow an "all-or-none" principle. "All" refers to early embryonic death leading to miscarriage, while "none" refers to normal embryonic development without abnormalities.
Three to Eight Weeks after Fertilization
This stage corresponds to organogenesis, during which the embryo undergoes directed differentiation and development. Exposure to harmful medications during this period may result in structural abnormalities, known as teratogenic-sensitive periods. For instance, neural tissue is most vulnerable between days 15–25 post-fertilization, the heart between days 21–40, and the limbs and eyes between days 24–46.
Nine Weeks after Fertilization to Term
This stage involves fetal growth, organ development, and functional maturation. During this period, only the nervous system, reproductive organs, and teeth continue to undergo differentiation, with neurological development peaking in late pregnancy and the neonatal stage. Exposure to medications during this time may lead to fetal damage due to immature liver enzyme functions and high blood-brain permeability. Effects can include fetal growth restriction, low birth weight, and functional or behavioral abnormalities in neonates.
The teratogenic risk increases markedly with prolonged or chronic exposure to harmful agents, whereas short-term exposure rarely leads to teratogenic effects. Generally, higher exposure dosages lead to greater harm to the embryo or fetus. Due to the heightened sensitivity of embryos to harmful factors, adverse effects on the embryo may occur at exposure levels that do not noticeably affect the mother.
Medication counseling should consider both the duration of exposure and the dosage, requiring a comprehensive evaluation to assess risks effectively.