Prescribing in Pregnancy and Breastfeeding: The Principles and the Blacklist

Principle one: the illness is a risk too

Every prescribing decision in pregnancy has two sides of a scale. On one side sits the risk of the drug to the fetus. On the other — and students forget this half constantly — sits the risk of leaving the maternal condition untreated. An uncontrolled illness is rarely neutral for the pregnancy. Poorly controlled epilepsy risks seizures and sudden death; unmanaged asthma starves the fetus of oxygen; untreated hypertension leads to pre-eclampsia and placental failure; an untreated infection can cause miscarriage or preterm labour; venous thromboembolism (VTE) remains a leading cause of maternal death; and untreated maternal depression carries real risk to mother and child. The correct question is never "is this drug completely safe?" — almost none are proven so — but "is the treated illness safer than the untreated illness?" This is the same benefit-versus-risk logic taught in the Principles of Pharmacology section, applied where the stakes are doubled.

Principle two: timing decides the harm

The same drug can be harmless in one week and disastrous in another, because the fetus is a different creature at each stage. The first trimester is the period of organogenesis — organs are being built — and this is the window of teratogenesis, when a drug can cause structural malformations. A neural-tube defect, a heart defect, a limb reduction: these are first-trimester injuries. The second and third trimesters are about growth and function, so later drug effects are different — impaired growth, functional or neurodevelopmental damage, and problems for the newborn (neonatal withdrawal, bleeding, respiratory depression, or the premature closure of a fetal blood vessel). A useful mental rule: early exposure threatens the fetal blueprint; late exposure threatens fetal growth, physiology, and the neonate. Some drugs are dangerous in one window and acceptable in the other — NSAIDs are the classic example, tolerated earlier but hazardous late in pregnancy.

Pregnancy also rewrites pharmacokinetics. The maternal body of pregnancy is not the body the drug was studied in. Plasma volume expands, so the volume of distribution rises and a water-soluble drug is diluted. Renal blood flow and glomerular filtration climb by roughly half, so renally-cleared drugs are eliminated faster and their levels may fall. Plasma albumin falls, altering protein binding and the free fraction of highly-bound drugs. Hepatic enzyme activity shifts. The practical consequence is that a dose that worked before pregnancy may become subtherapeutic — a reason certain drugs (such as some antiepileptics and levothyroxine) need their levels tracked and doses adjusted as pregnancy advances, rather than left untouched. These are the same absorption-distribution-metabolism-excretion principles from the Principles of Pharmacology section, now moving targets.

The blacklist: teratogens to know cold

A prescriber cannot memorise every drug — but must know the true teratogens by heart. Warfarin is the archetype: it crosses the placenta and causes fetal warfarin syndrome (nasal hypoplasia, stippled epiphyses) plus fetal bleeding — replaced in pregnancy by low-molecular-weight heparin (LMWH), which does not cross the placenta. This links to the Cardiovascular and antithrombotic chapters. ACE inhibitors and ARBs damage the developing fetal kidneys and skull (oligohydramnios, renal failure, hypocalvaria) and are avoided throughout — the pregnancy antihypertensives are labetalol, nifedipine and methyldopa instead. Sodium valproate and, to varying degrees, other antiepileptics cause neural-tube defects and a well-documented neurodevelopmental syndrome; valproate is now essentially contraindicated in any woman of childbearing potential unless she is in a strict pregnancy-prevention programme. This ties to the Central Nervous System section, where the antiepileptics are taught in full. Isotretinoin and other retinoids are among the most powerful teratogens known — severe craniofacial, cardiac and CNS defects — and are dispensed only under a formal pregnancy-prevention programme (see the Dermatology chapter). Methotrexate and mycophenolate are abortifacient and teratogenic (methotrexate as a folate antagonist; see the Inflammation section). Lithium carries a specific risk of Ebstein's anomaly, a cardiac defect (Central Nervous System / mood stabilisers).

The blacklist continues with several antimicrobials and a few late-pregnancy hazards. Tetracyclines deposit in developing teeth and bone, staining teeth and impairing growth, so they are avoided from mid-pregnancy; fluoroquinolones are linked to cartilage damage in animal studies and avoided; aminoglycosides (gentamicin) risk fetal ototoxicity. Trimethoprim is a folate antagonist and is avoided in the first trimester (relevant to the neural tube). NSAIDs are the classic timing drug: broadly avoided in the third trimester because they can trigger premature closure of the ductus arteriosus and cause oligohydramnios by reducing fetal renal perfusion. Androgens and the 5α-reductase inhibitor finasteride can virilise or disrupt development of a male fetus — finasteride is teratogenic and women should not even handle crushed or broken tablets. Finally, live vaccines (MMR, varicella, yellow fever) are generally avoided in pregnancy because of the theoretical risk of transmitting the live organism to the fetus. The list is long enough to respect and short enough to memorise — and memorising it is non-negotiable.

The safer choices, scenario by scenario

Reassuringly, most common problems have a well-mapped safe route. Preconception and early pregnancy: folic acid to reduce neural-tube defects (high dose for higher-risk women, including those on antiepileptics). Hypertension: labetalol, methyldopa or nifedipine — never an ACE inhibitor or ARB (see the Pregnancy-hypertension chapter). Anticoagulation and VTE prevention: LMWH throughout. Infection: penicillins, cephalosporins and macrolides (e.g. erythromycin) are the workhorses (see the Antimicrobials section for which antibiotics are safe and which are not). Pain and fever: paracetamol is the analgesic of choice; NSAIDs are avoided late, and opioids used cautiously near term because of neonatal withdrawal and respiratory depression. Diabetes: insulin and metformin are used, with labetalol for co-existing hypertension. Mental illness: some SSRIs are used when the benefit justifies it, weighing the small neonatal risks against the real danger of untreated maternal depression (see the Central Nervous System section). Asthma: inhaled therapy is continued — a controlled airway protects the fetus. The unifying theme is that a safe, effective option almost always exists; the skill is knowing it, not abandoning treatment.

Breastfeeding: mostly reassuring

The milk is a far weaker route of exposure than the placenta. The dose an infant receives through breast milk is usually a tiny fraction of the maternal dose, so the great majority of drugs are compatible with breastfeeding — and the mistake to avoid is discouraging breastfeeding unnecessarily. A few considerations matter: the relative infant dose (how much of the maternal dose reaches the baby), the drug's oral bioavailability in the infant, and the vulnerability of the neonate (especially a premature or unwell one). Some drugs genuinely warrant caution. Codeine is the cautionary tale — a mother who is a CYP2D6 ultra-rapid metaboliser converts it to unexpectedly high morphine levels that can cause life-threatening sedation in the breastfed infant, which is why it is avoided. High-dose aspirin is avoided (Reye's syndrome risk and bleeding), as are some sedating psychotropics, and — absolutely — radioactive isotopes and cytotoxic (chemotherapy) drugs, which require stopping or interrupting breastfeeding. The right move is never to guess: check a dedicated resource — the BNF, the LactMed database, or UKTIS / the "bumps" (best use of medicines in pregnancy) service — which give drug-specific pregnancy and lactation guidance far better than memory.