USMLE Step 1: Teratogens Drill

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Comprehensive Step 1 Teratogen Master Table

Medications and Chemical Agents

Teratogen	Classic Clinical Findings (High-Yield)	Key Notes / Mechanism
ACE Inhibitors / ARBs	Renal dysgenesis, oligohydramnios (leads to Potter sequence), hypocalvaria (skull defects).	Contraindicated in all trimesters; affects fetal blood pressure/renal development.
Alkylating Agents	Absence of digits, multiple anomalies.	Chemotherapy drugs (e.g., cyclophosphamide).
Aminoglycosides	Ototoxicity (CN VIII damage).	"A mean guy hits the baby in the ear."
Carbamazepine	Neural tube defects (spina bifida), fingernail hypoplasia, craniofacial defects.	Cytochrome P450 inducer; often used for trigeminal neuralgia or seizures.
Diethylstilbestrol (DES)	Clear cell adenocarcinoma of the vagina, Müllerian anomalies in daughters.	Historically used to prevent miscarriage.
Fluoroquinolones	Cartilage damage (arthropathy).	Think: "Fluoroquinolones hurt the bones (and attachments)."
Isotretinoin	Severe microcephaly, thymic aplasia, cardiovascular defects.	Vitamin A derivative; requires two forms of contraception and a negative pregnancy test.
Lithium	Ebstein anomaly (apical displacement of tricuspid valve, "atrialization" of the right ventricle).	Used for bipolar disorder.
Methimazole	Aplasia cutis congenita (focal absence of skin on the scalp).	Used for hyperthyroidism. Use PTU (Propylthiouracil) in the 1st trimester instead.
Methotrexate	Neural tube defects, spontaneous abortion.	Folate antagonist.
Phenytoin	Fetal Hydantoin Syndrome: Cleft lip/palate, congenital heart disease, hypoplastic nails/digits.	Related to folate interference and oxidative metabolites.
Statins	CNS and limb defects.	Generally contraindicated.
Sulfonamides	Kernicterus (bilirubin-induced neurological damage).	Displace bilirubin from albumin; avoid in the 3rd trimester.
Tetracyclines	Discolored teeth, inhibited bone growth.	"Teeth-tracyclines."
Thalidomide	Phocomelia (flipper-like limbs).	Historically used for morning sickness; now used for leprosy and multiple myeloma.
Valproate	Neural tube defects (highest risk of all AEDs).	Inhibits maternal folate absorption.
Vitamin A (Excess)	Spontaneous abortion, cleft palate, cardiac abnormalities.	Similar mechanism to Isotretinoin.
Warfarin	Nasal hypoplasia, stippled epiphyses (bone abnormalities).	"Do not wage warfarin on the baby." Use Heparin instead (does not cross placenta).

Social and Environmental Factors

Teratogen	Classic Clinical Findings	Key Notes / Mechanism
Alcohol	Fetal Alcohol Syndrome (FAS): Smooth philtrum, thin upper lip, small palpebral fissures, microcephaly, intellectual disability.	Leading cause of intellectual disability in the US.
Cocaine	Low birth weight, placental abruption, preterm birth.	Due to severe fetal/placental vasoconstriction.
Smoking (Nicotine)	Low birth weight (intrauterine growth restriction), preterm labor, SIDS.	Nicotine causes vasoconstriction; CO displaces O2 from hemoglobin.
Methylmercury	Neurotoxicity similar to cerebral palsy.	Often found in large fish (e.g., shark, swordfish).
Ionizing Radiation	Microcephaly, intellectual disability.	Usually associated with high-dose therapeutic radiation, not standard X-rays.

Maternal Health Conditions & Infections

Condition	Classic Clinical Findings	Key Notes / Mechanism
Maternal Diabetes	Caudal regression syndrome (anal atresia to sirenomelia), macrosomia, transposition of great vessels, VSD.	Strictly controlled glucose levels minimize risk.
Maternal Phenylketonuria	Microcephaly, intellectual disability, congenital heart defects.	Caused by high maternal levels of phenylalanine crossing the placenta.
Parvovirus B19	Hydrops fetalis (severe fetal anemia/edema).	"Slapped-cheek" rash in the mother.
Toxoplasmosis	Chorioretinitis, hydrocephalus, intracranial calcifications.	"The Classic Triad." Avoid cat litter and undercooked meat.
Syphilis	Saber shins, saddle nose, Hutchinson teeth, mulberry molars.	CN VIII deafness is also common.

High-Yield Mnemonics and Tips

• Valproate: Think Valproate = Very high risk for Neural Tube Defects (inhibits folate).
• ACE Inhibitors: Think ACE = Anuria/Oligohydramnios, Calvaria (skull) defects, Extremity contractions (Potter sequence).
• Warfarin vs. Heparin: "Warfarin crosses the ponderous placenta (large/bad), Heparin stays in the hep-house (safe)."
• FAS Facial Features: To remember the philtrum and lip, imagine a "smooth" upper face with "short" eyes (palpebral fissures).
• "C"arbamazepine: Think Cranial/Neural tube defects.
• "S"ulfonamides: Think Secondary jaundice (Kernicterus).
• "M"ethimazole: Think Missing skin (Aplasia cutis).
• "P"henytoin: Think Pinkies (hypoplastic nails/digits).

Comparative "Red Flag" Guide

• Maternal Acne: Isotretinoin → Microcephaly/Thymic aplasia.
• Maternal Bipolar: Lithium → Ebstein Anomaly (Tricuspid valve).
• Maternal Seizures: Phenytoin → Fingernail hypoplasia. Valproate/Carbamazepine → Spina Bifida.
• Maternal Hyperthyroidism: Methimazole → Scalp defects (Aplasia cutis).
• Maternal Clot/PE: Warfarin → Stippled epiphyses/Nasal hypoplasia (Use Heparin instead).