Prescribing in Pregnancy
All medicines cross the placenta to some extent.
When medicines are prescribed for pregnant women, either for acute or chronic conditions, weigh the potential benefits to the mother against the risk of adverse effects on the fetus/neonate.
Dosages of medicines may need to be adjusted during pregnancy as medicines may have altered pharmacokinetics, typically increased clearance due to increased organ blood flow and enzyme induction.
General Advice
- Medicines can have harmful effects on the embryo or fetus at any time during pregnancy. It is important to bear this in mind when prescribing for a woman of child-bearing age or for men trying to father a child.
- During the first trimester medicines can produce congenital malformations (teratogenesis), and the period of greatest risk is from the third to the eleventh week of pregnancy. Medicines with long half-life given pre-conception may confer risk even if ceased before or early in pregnancy.
- During the second and third trimesters, medicines can affect the growth or functional development of the fetus, or they can have toxic effects on fetal tissues (e.g. teeth, bones, kidney, brain, and nervous system).
- Medicines given shortly before term or during labour can have adverse effects on labour or on the neonate after delivery (e.g. withdrawal syndrome).
- Not all the damaging effects of intrauterine exposure to medicines are obvious at birth. Some may only manifest later in the child’s life. Such late-onset effects include malignancy, e.g. adenocarcinoma of the vagina after puberty in females exposed to diethylstilbestrol in utero, and adverse effects on intellectual, social, and functional development.
- For general advice, see Individualising Drug Therapy, including: consider non-medicine measures first; avoid all medicine 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. diabetes, asthma, epilepsy, inflammatory conditions) may carry a higher fetal and/or pregnancy risk than medicine treatment.
- If medicine treatment is necessary, use medicines with a more established safety record.
- Use the lowest effective dose for the shortest possible time.
- Seek advice (e.g. from Medicines Information
80900) because:- readily available references usually offer little in terms of risk assessment.
- grading systems are over-simplified. Clinical context is important.
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Effect of Medicines on Pregnancy, Fetus, or Neonate
Medicine toxicity in pregnancy, including teratogencity
- Approximately 2 to 4% of all live births (i.e., regardless of in utero exposure to medicines) are associated with a fetal abnormality. Of these, medicines are responsible for 1 to 5% (i.e. affecting < 0.2% of all live births).
- Complementary and alternative products may also cause fetal abnormalities – seek specialist advice (e.g. Medicines Information).
- If pregnancy is planned or known, medicine-associated malformations may be preventable.
- Accurate timing of medicine exposure and examination of the medicine pharmacokinetics may help determine the risk.
- Some medicines are abortifacient (e.g. misoprostol, methotrexate).
- Some antihypertensives may reduce placental perfusion, potentially causing fetal hypoxia and in utero growth retardation.
- NSAIDs cause premature closure of the ductus arteriosus in the third trimester.
Medicines with proven toxicity in humans
- ACE inhibitors (e.g. perindopril)
- alcohol
- amiodarone
- antiepileptic (especially valproate sodium)
- carbimazole
- cytotoxic agents (e.g. methotrexate)
- leflunomide
- lithium carbonate
- misoprostol
- retinoids (e.g. isotretinoin)
- tetracyclines (e.g. doxycycline)
- thalidomide (and analogues)
- trimethoprim (first trimester)
- warfarin
Note: occasionally a known teratogen may be clinically necessary, but alternatives should be considered. If used, this should be prescribed and supervised by a specialist – consult with Obstetric Medicine
Predictable Risks Based on Drug Activity
- Beta-agonists and NSAIDs may delay birth
- Withdrawal reactions or excessive clinical effects may be observed in neonates after in utero exposure to some medicines (e.g. respiratory depression in neonate from maternal use of opioids).
Effects of Pregnancy on Medicine Pharmacokinetics
- Most medicines undergo increased clearance during pregnancy due to increased organ blood flow and enzyme induction. For a given dose of medicine, this is expected to result in decreased concentrations and decreased effect.
- Therapeutic Drug Monitoring (TDM) provides a guide to account for changes in concentration. Protein binding changes in pregnancy and this may affect the interpretation of some medicine concentrations (e.g. carbamazepine), so measuring free drug concentration is useful for medicines.
- Dose adjustment is complicated during pregnancy (e.g. lamotrigine, levetiracetam) especially peripartum. Seek specialist advice (e.g. Medicines Information 80900).
Topic Code: 93259
