Prescribing in Pregnancy and Breastfeeding
Key points
- Principle: prescribe the lowest effective dose of the best-evidenced drug for the shortest necessary time, and never stop a needed medication without checking the alternative risk of undertreated disease.
- First trimester: the period of organogenesis (weeks 3-8) carries the highest teratogenic risk; the embryo is relatively protected before implantation ('all or nothing').
- Absolute avoid list: sodium valproate, ACE inhibitors/ARBs, warfarin, methotrexate, isotretinoin, and most statins are teratogenic or contraindicated.
- Safer alternatives: labetalol/nifedipine for hypertension, LMWH for anticoagulation, levetiracetam/lamotrigine for epilepsy where possible, and penicillins for infection.
- Breastfeeding: most drugs pass into breast milk in small amounts; the decision weighs infant drug exposure against the benefits of breastfeeding and the risk of untreated maternal disease.
- Key resource: the BNF and UKTIS (UK Teratology Information Service) should be checked for any drug outside routine obstetric practice.
- NSAIDs: avoided from 30 weeks due to risk of premature ductus arteriosus closure and oligohydramnios; used cautiously earlier.
- Folic acid: 5 mg (high-dose) rather than 400 microgram is used in women on antiepileptics, with diabetes, obesity, or a previous neural tube defect.
Introduction
Roughly nine in ten pregnant women take at least one medicine during pregnancy, and many have chronic conditions - epilepsy, hypertension, diabetes, depression - that cannot simply be left untreated.1 Prescribing safely in pregnancy is therefore not about avoiding all drugs, but about weighing the risk of drug exposure to the fetus against the risk of undertreated maternal disease, which itself often carries fetal risk.
This article covers the general principles and the specific drugs most commonly tested in UKMLA-style questions. It is a foundational companion to the pregnancy-specific articles on hypertension, gestational diabetes and venous thromboembolism, which give the full prescribing detail for those conditions.
Principles of teratogenicity
Drug risk to the fetus depends heavily on timing.2
| Stage | Timing | Effect of drug exposure |
|---|---|---|
| Pre-implantation | Weeks 0-2 | 'All or nothing' - the embryo is either unaffected or does not survive; structural malformation is rare |
| Organogenesis | Weeks 3-8 | Highest risk of structural teratogenesis (major malformations of organs and limbs) |
| Fetal period | Weeks 9 to term | Organs are formed; exposure now causes growth restriction, functional or minor structural defects rather than major malformation |
| Late third trimester / peripartum | Weeks 30+ | Risk of effects on labour, delivery and neonatal adaptation (e.g. withdrawal, floppy baby syndrome) |
A drug's placental transfer also depends on its size, lipid solubility, protein binding and ionisation - small, lipophilic, unbound and unionised drugs cross most readily. In practice, assume any drug crosses the placenta to some degree unless there is specific evidence otherwise.
Drugs to avoid in pregnancy
A relatively short list of drugs accounts for most of what is tested, and each has a distinct, memorable mechanism of harm.3
| Drug/class | Risk | Notes |
|---|---|---|
| Sodium valproate | Neural tube defects, developmental delay, autism spectrum disorder | Contraindicated unless no alternative under the Valproate Pregnancy Prevention Programme |
| ACE inhibitors / ARBs | Fetal renal impairment, oligohydramnios, skull ossification defects | Switch to labetalol or nifedipine before conception where possible |
| Warfarin | 'Warfarin embryopathy' - nasal hypoplasia, stippled epiphyses; fetal/intracranial haemorrhage later | Switch to LMWH, ideally before 6 weeks' gestation |
| Methotrexate | Multiple malformations ('fetal methotrexate syndrome'), miscarriage | Stop at least 3-6 months before conception (both partners) |
| Isotretinoin | Severe craniofacial, cardiac and CNS malformations | Pregnancy Prevention Programme mandates contraception |
| Statins | Theoretical risk of cholesterol-dependent embryogenesis disruption | Stopped in pregnancy; evidence is weaker than for the drugs above but practice is cautious |
| Lithium | Cardiac malformations (classically Ebstein's anomaly) if used in first trimester | Weigh against relapse risk in bipolar disorder; monitor levels closely if continued |
| Tetracyclines (e.g. doxycycline) | Discoloured teeth, inhibited bone growth | Avoid throughout pregnancy |
| Trimethoprim | Folate antagonist - neural tube defects | Avoid particularly in the first trimester; give with folic acid if unavoidable |
| NSAIDs (from ~30 weeks) | Premature closure of the ductus arteriosus, oligohydramnios, delayed labour | Short-term, low-dose use earlier in pregnancy is generally acceptable |
| Aminoglycosides (e.g. gentamicin) | Fetal ototoxicity and nephrotoxicity | Use only if benefit clearly outweighs risk, with level monitoring |
Safer alternatives for common chronic conditions
Hypertension
Labetalol is first-line; nifedipine (modified-release) and methyldopa are alternatives. ACE inhibitors and ARBs are avoided (see above). Full detail is in the article on hypertension in pregnancy.
Epilepsy
Levetiracetam and lamotrigine have the most reassuring safety data and are preferred where seizure control allows. Valproate is avoided wherever possible. Anticonvulsants are continued through pregnancy in most cases because uncontrolled seizures pose a greater risk to mother and fetus than most anticonvulsant exposure - the decision to switch or stop is made with a neurologist, ideally before conception, and high-dose (5 mg) folic acid is given.4
Diabetes
Metformin and insulin are both used in pregnancy; most other oral hypoglycaemics are avoided. Full detail is in the article on gestational diabetes.
Anticoagulation
Low molecular weight heparin (LMWH, e.g. enoxaparin) is the anticoagulant of choice throughout pregnancy - it does not cross the placenta. Warfarin is teratogenic and DOACs are avoided due to insufficient safety data. Full detail is in the article on venous thromboembolism in pregnancy.
Depression and anxiety
SSRIs (e.g. sertraline) are generally continued if a woman is stable on treatment, as the risks of untreated depression (poor engagement with antenatal care, self-harm, impaired bonding) usually outweigh drug risk. Paroxetine is best avoided due to an association with fetal cardiac defects. Late third-trimester exposure to SSRIs can cause transient neonatal adaptation symptoms (jitteriness, poor feeding), which are usually mild and self-limiting.
Infection
Penicillins, cephalosporins and macrolides (except clarithromycin, which is avoided) are considered safe. Nitrofurantoin is avoided at term due to a theoretical risk of neonatal haemolysis, and trimethoprim is avoided in the first trimester (see above).
Supplements in pregnancy
Folic acid
Folic acid reduces the risk of neural tube defects, and because the neural tube closes by around day 28 - often before a woman knows she is pregnant - it must be started before conception to be effective, ideally at least one month before, and continued until the end of the 12th week.1
| Dose | Who it applies to |
|---|---|
| 400 micrograms daily | All women planning a pregnancy or in the first trimester (standard dose) |
| 5 mg daily (high dose) | Previous pregnancy affected by a neural tube defect; the woman or her partner has a neural tube defect, or a family history of one; diabetes mellitus; BMI 30 or above; taking antiepileptic drugs; sickle cell disease, thalassaemia or other haemolytic anaemia; coeliac disease or other malabsorption |
Vitamin D
All pregnant and breastfeeding women are advised to take 10 micrograms (400 units) of vitamin D daily throughout pregnancy and while breastfeeding, to support fetal bone development and prevent maternal deficiency. Higher doses are considered in women at increased risk of deficiency, such as those with darker skin, limited sun exposure, or obesity.
What to avoid
Vitamin A (retinol) supplements and liver/liver products should be avoided in pregnancy, as high-dose vitamin A is teratogenic - this is the same mechanism that makes isotretinoin so hazardous. Standard pregnancy multivitamins are formulated without retinol for this reason, which is why a general over-the-counter multivitamin is not an appropriate substitute.
Vaccination in pregnancy
Inactivated vaccines are safe and recommended: influenza (any trimester) and pertussis (from 16 weeks, to transfer protective maternal antibodies to the neonate before the primary immunisation schedule starts). Live attenuated vaccines (MMR, varicella, yellow fever, BCG) are avoided in pregnancy because of a theoretical risk to the fetus, and pregnancy should be avoided for one month after a live vaccine is given.
Prescribing in breastfeeding
Almost all drugs pass into breast milk to some extent, but the absolute dose reaching the infant is usually very small. The decision to prescribe balances infant drug exposure, the benefits of breastfeeding for both mother and infant, and the risk of undertreated maternal disease if breastfeeding is stopped to accommodate a drug.5
Drug factors that predict low transfer into milk and low infant risk include high maternal protein binding, low lipid solubility, a large molecular size, and a short half-life. Neonates - particularly those born preterm or with reduced hepatic/renal clearance - are more vulnerable to accumulation than older infants.
| Drug/class | Compatible with breastfeeding? |
|---|---|
| Penicillins, cephalosporins | Yes - considered safe |
| Warfarin, heparin/LMWH | Yes - negligible transfer into milk |
| Labetalol, nifedipine | Yes |
| Sertraline, most SSRIs | Generally yes - preferred over drugs with less data |
| Amiodarone | Avoid - high iodine content, accumulates in milk |
| Lithium | Avoid - narrow therapeutic index, significant transfer |
| Methotrexate, cytotoxic drugs | Avoid |
| Codeine | Avoid - unpredictable maternal metabolism can cause neonatal opioid toxicity |
| Aspirin (regular, analgesic dose) | Avoid - theoretical risk of Reye's syndrome; low-dose (75 mg) aspirin for pre-eclampsia prophylaxis is compatible |
Sources of prescribing information
For any drug outside routine obstetric practice, check the BNF (which flags pregnancy and breastfeeding cautions for every entry) and the UK Teratology Information Service (UKTIS), which provides individualised risk assessments based on the specific drug, dose and gestation.6 Medicines optimisation should always be a shared decision with the woman, explaining both the risk of the drug and the risk of leaving her condition untreated.
Red flags
Prognosis
With careful medicine selection, most women with chronic conditions have healthy pregnancies. Pre-conception counselling - ideally starting before contraception is stopped - allows time to switch to safer alternatives, optimise disease control, and start high-dose folic acid where indicated, and is consistently associated with better maternal and fetal outcomes than reactive management once pregnancy is already confirmed.
References
- NICE Clinical Knowledge Summaries (CKS). Prescribing in pregnancy. Available here
- UK Teratology Information Service (UKTIS). Available here
- BNF. Guidance on prescribing - pregnancy. Available here
- MHRA. Valproate use by women and girls. Available here
- BNF. Guidance on prescribing - breastfeeding. Available here
- NICE NG192. Intrapartum care - medicines guidance cross-reference. Available here
This article is written for revision and education. It is not clinical guidance and must not be used to make decisions about the care of a patient. Always check current NICE guidance and local protocols.