Warfarin, retinoids, ACE inhibitors, valproate and tetracyclines among others
Mnemonic
The classic teratogens, each with its lesion:
- ACE inhibitors and angiotensin receptor blockers - renal dysgenesis, oligohydramnios
- Warfarin - nasal hypoplasia, stippled epiphyses, fetal haemorrhage
- Sodium valproate - neural tube defects, the highest risk antiepileptic
- Phenytoin - fetal hydantoin syndrome, cleft lip and palate
- Isotretinoin and high dose vitamin A - severe craniofacial and cardiac defects
- Methotrexate - abortifacient, skeletal defects
- Tetracyclines - teeth and bone discolouration
- Aminoglycosides - ototoxicity
- Trimethoprim - a folate antagonist, avoided in the first trimester
- Nitrofurantoin - haemolysis, avoided at term
- NSAIDs - premature closure of the ductus arteriosus in the third trimester
- Lithium - Ebstein’s anomaly
- Thalidomide - phocomelia
“Trimethoprim early, nitrofurantoin late” is the pair to remember for urinary infection: each is avoided at the opposite end of pregnancy.
Epilepsy is the case where the drug is usually safer than the disease: uncontrolled seizures carry a greater risk than most antiepileptics, so treatment is optimised preconception with high dose folate rather than stopped.
Expansion
| Drug | Effect |
|---|---|
| Sodium valproate | Neural tube defects, neurodevelopmental harm; highest risk antiepileptic |
| Warfarin | Chondrodysplasia punctata in the first trimester, fetal haemorrhage later |
| ACE inhibitors and ARBs | Renal dysgenesis, oligohydramnios, skull defects |
| Retinoids (isotretinoin) | Craniofacial, cardiac and CNS malformations; extremely potent |
| Methotrexate | Multiple malformations, abortifacient |
| Tetracyclines | Tooth discolouration, bone growth inhibition |
| Aminoglycosides | Ototoxicity |
| Lithium | Ebstein anomaly |
| Carbimazole | Aplasia cutis |
| Phenytoin | Fetal hydantoin syndrome |
| NSAIDs (third trimester) | Premature closure of the ductus arteriosus |
| Alcohol | Fetal alcohol syndrome |
Timing determines the effect: exposure before implantation is all or nothing; weeks 3 to 8 (organogenesis) causes structural malformation; later exposure causes growth and functional effects.
Relatively safe and commonly needed: paracetamol, penicillins and cephalosporins, methyldopa, labetalol, nifedipine, insulin, low molecular weight heparin (which does not cross the placenta).
The practical principle is that untreated maternal illness is often more dangerous than the drug, particularly for epilepsy, asthma and infection.