Pregnant women may need medicines for pre-existing conditions or problems related to pregnancy. Any drug taken during pregnancy can reach the fetus and may cause harm depending on the stage of fetal development. Safe prescribing requires understanding how drugs cross the placenta, how pregnancy changes drug handling, and which medicines are safe or unsafe.
Fetal Development and Drug Effects
Drug effects depend on the stage of pregnancy during which exposure occurs:
- Blastogenesis (first 15–21 days): Early cell division; embryo is less differentiated.
- Organogenesis (14–56 days): Major organs form. Drug exposure may cause structural birth defects.
- Fetal period (9th week to birth): Organs mature. Drugs may cause growth problems or functional toxicity.
Placental Transfer of Drugs
The placenta connects mother and fetus. It performs nutrition, metabolism, respiration and excretion functions. Drugs usually cross via passive diffusion; therefore, the placenta is not a barrier.
Factors Affecting Placental Drug Transfer
- Molecular weight: <500 Da cross easily; large molecules (e.g., heparin) do not cross.
- pH: Weak acids and bases cross readily.
- Lipid solubility: Moderately lipid-soluble drugs cross easily.
- Absorption changes: Slower gastric emptying prolongs absorption.
- Distribution changes: Increased plasma volume and cardiac output during pregnancy.
- Placental thinning: Progressively increases drug transfer.
- Disease conditions: Hypertension or diabetes may increase or reduce drug transfer.
FDA Pregnancy Risk Categories
The FDA classifies drugs based on risk to the fetus:
- Category A: Safe; controlled studies show no fetal risk.
- Category B: Animal studies safe; no controlled studies in humans.
- Category C: Animal studies show harm; use only if benefit outweighs risk.
- Category D: Proven human fetal risk; may be used only in serious situations.
- Category X: Proven fetal abnormalities; contraindicated in pregnancy.
Teratogenic & Potentially Toxic Drugs
- Vitamin A derivatives (retinoids including isotretinoin)
- ACE inhibitors
- Warfarin
- Estrogens and androgens
- Ethanol
- Tetracyclines, metronidazole, quinolones
- Lithium
- Anticonvulsants (phenytoin, valproic acid, trimethadione)
- Anticancer drugs (cyclophosphamide, methotrexate, busulfan)
- Finasteride
Other Fetotoxic Effects
- CNS depression: barbiturates, narcotics, antidepressants
- Neonatal bleeding: NSAIDs, anticoagulants
- Drug withdrawal: narcotics, benzodiazepines, barbiturates
- Reduced birth weight: alcohol, smoking, substance abuse
Pharmacokinetic Changes in Pregnancy
- Absorption: slower GI motility → delayed absorption.
- Volume of distribution: increases due to higher plasma volume.
- Protein binding: reduced serum proteins → higher free drug levels.
- Renal clearance: GFR increases up to 150% → increased elimination of renally cleared drugs.
- Hepatic clearance: increased metabolism of many drugs.
General Prescribing Principles in Pregnancy
- Involve parents in decision making.
- Treat only when necessary; avoid drugs in the first trimester if possible.
- Weigh benefits vs. risks carefully.
- Use well-established drugs at the lowest effective dose.
- Avoid polypharmacy.
- Monitor pregnancy progression and adjust doses accordingly.
- Document discussions, risks, and decisions.
- Monitor the newborn for withdrawal or adverse effects.
Breast Feeding and Drug Safety
Breastfeeding benefits both mother and baby. Most medicines pass into breast milk, but usually in low amounts that do not harm the infant. However, some drugs concentrate in milk or have harmful effects on the newborn.
Factors Affecting Drug Excretion in Milk
- Maternal metabolism may activate or inactivate drugs.
- Prolactin regulates milk production.
Drugs That Decrease Prolactin
- Ergot alkaloids
- L-dopa
- Bromocriptine
Drugs That Increase Prolactin
- Metoclopramide
- Methyldopa
- Amphetamines
- Haloperidol
- Phenothiazines
- Theophylline
Drugs That Enter Breast Milk Easily
- Narcotics, barbiturates, benzodiazepines → cause sedation in infants
- Antidepressants, antipsychotics
- Metoclopramide → CNS effects
- Anticholinergics → CNS effects
Clinical Decision Making
Prescribing in pregnancy and breastfeeding is challenging. Being too cautious may cause untreated maternal disease; being too careless may harm the fetus or infant. Balanced, evidence-based decisions with good patient counselling are essential.
Detailed Notes:
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