All drugs cross the placenta to some extent.
General Advice
- Consider non-drug measures first; avoid all drug therapy if possible, especially in the first trimester.
- Use particular care when prescribing for women of childbearing potential. Half of all pregnancies are unplanned.
- Poor disease control (e.g. asthma, epilepsy) may carry a higher foetal risk than drug treatment.
- If drug treatment is necessary, use drugs with a more established safety record.
- Use the lowest effective dose for the shortest possible time.
- Readily seek advice because:
- Readily available references usually offer little in terms of risk assessment.
- Grading systems are over-simplified. Clinical context is important.
Effect of Drugs on Pregnancy, Foetus, or Neonate
Teratogenicity
- Approximately 2 to 4% of live births are associated with a foetal abnormality. Of these, drugs are responsible for 1 to 5% (i.e. affecting < 0.2% of all live births).
- If pregnancy is planned or known, drug-associated malformations may be preventable.
- Accurate timing of drug exposure and examination of the drug pharmacokinetics may help determine the risk.
Drugs with proven teratogenicity in humans
Note: This list is not exhaustive.
| ACE inhibitors | Cytotoxic agents | Tetracyclines (e.g. Doxycycline) |
| Alcohol | Leflunomide | Thalidomide |
| Amiodarone | Lithium | Trimethoprim (1st trimester) |
| Androgens (not accidental oral contraceptive use) | Methotrexate | Warfarin |
| Anticonvulsants (especially valproate sodium) | Misoprostol | |
| Carbimazole | Retinoids (e.g. Isotretinoin) |
Predictable Risks Based on Drug Activity
- NSAIDs cause premature closure of the ductus arteriosus in the third trimester.
- Some antihypertensives may reduce placental perfusion, potentially causing foetal hypoxia and in utero growth retardation.
- Withdrawal reactions or excessive clinical effects may be observed in neonates after in utero exposure to some drugs (e.g. respiratory depression in neonate from maternal use of opioids).
- Beta-agonists and NSAIDs may delay delivery.
- Some drugs are abortifacient (e.g. misoprostol).
Effects of Pregnancy on Drug Pharmacokinetics
- Most drugs undergo increased clearance during pregnancy due to increased organ blood flow and enzyme induction.
- Therapeutic Drug Monitoring (TDM) is complicated during pregnancy (e.g. lamotrigine). Seek specialist advice (e.g. Medicines Information)
- Protein binding changes in pregnancy and this may affect the interpretation of some drug concentrations (e.g. phenytoin).