Learning Objectives
Master the Comprehensive List of Teratogens and their specific clinical impacts. Understand the windows of susceptibility and recognize the distinct “signature” defects associated with specific medications and maternal conditions for the USMLE Step 1.
1. Principles of Teratogenicity
Susceptibility to teratogens varies with the developmental stage at the time of exposure.
| Period | Timing | Effect |
|---|---|---|
| Pre-implantation | Weeks 1–2 | “All-or-none” effect. |
| Embryonic Period | Weeks 3–8 | Organogenesis: Highest susceptibility to structural defects. |
| Fetal Period | Week 8+ | Affects growth and function. |
2. Teratogenic Medications
The following medications are known to cause specific, predictable malformations.
| Medication | Clinical Effect on Fetus |
|---|---|
| ACE Inhibitors | Renal failure, Oligohydramnios, and hypocalvaria. |
| Alkylating agents | Multiple anomalies (e.g., ear/facial abnormalities, absence of digits). |
| Aminoglycosides | Ototoxicity (“A mean guy hit the baby in the ear”). |
| Antiepileptics | Neural tube defects, cardiac defects, cleft palate, and phalanx/nail hypoplasia. (High-dose folate recommended). |
| Diethylstilbestrol | Vaginal clear cell adenocarcinoma, congenital Müllerian anomalies. |
| Fluoroquinolones | Cartilage damage. |
| Folate antagonists | Neural tube defects (Trimethoprim, Methotrexate). |
| Isotretinoin | Craniofacial, CNS, cardiac, and Thymic defects. (Contraception is mandatory). |
| Lithium | Ebstein anomaly (apical displacement of the tricuspid valve). |
| Methimazole | Aplasia cutis congenita (congenital absence of scalp skin). |
| Tetracyclines | Discolored teeth (“Teethracyclines”) and inhibited bone growth. |
| Thalidomide | Limb defects (Phocomelia/flipper limbs). |
| Warfarin | Stippled epiphyses (bone/cartilage deformities) and nasal hypoplasia. Use Heparin instead. |
3. Substance Use & Other Factors
Environmental exposures and maternal health states significantly influence fetal outcomes.
| Exposure | Effect on Fetus |
|---|---|
| Alcohol | Fetal Alcohol Syndrome (intellectual disability, facial dysmorphism). |
| Cocaine | Preterm birth and Fetal Growth Restriction (FGR) via vasoconstriction. |
| Tobacco | Low birth weight (leading cause in resource-rich areas), SIDS, and ADHD. |
4. Other Factors
Environmental exposures and maternal health states significantly influence fetal outcomes.
| Exposure | Effect on Fetus |
|---|---|
| Iodine (Lack/Excess) | Congenital hypothyroidism. |
| Maternal Diabetes | Caudal regression syndrome, transposition of great arteries (TGA), and Macrosomia. |
| Maternal PKU | Microcephaly, intellectual disability, and heart defects. |
| Methylmercury | Neurotoxicity (found in large predator fish). |
| X-rays | Microcephaly and intellectual disability. Lead shielding minimizes risk. |
Activity
High-Yield Mnemonics & Tips:
- Aminoglycosides: “A mean guy hit the baby in the ear” (Ototoxicity).
- Warfarin: “In war, you need strong bones to march and optics to see the enemy” (Bone deformities, Optic nerve atrophy).
- Maternal Diabetes: Classic for Caudal Regression Syndrome (agenesis of the sacrum/lumbar spine).
- Isotretinoin: Contraception is vital because of Thymic and cardiac malformations.