Pregnancy: Potential harm

Last updated: Tuesday, September 27, 2022

A drug does not need to cross the placenta to cause embryonic or fetal toxicity. For example, any drug that causes vasoconstriction of the placental vasculature can cause harm. However, almost all drugs do cross the placenta, mostly by simple diffusion. The extent to which compounds will cross the placenta depends upon their molecular size, degree of ionisation, protein binding and lipid solubility:

  • Non-ionised, lipid-soluble drugs will cross in preference to polar, ionised, hydrophilic compounds (e.g. the more lipid-soluble labetalol will cross the placenta to a greater extent than the more hydrophilic atenolol).

  • Drugs with a high molecular weight tend not to cross the placenta (e.g. insulin, heparin) but there are exceptions (e.g. infliximab, adalimumab).

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Although malformations are the most obvious adverse pregnancy outcome that medicines can cause, there are others including the following:

  • Spontaneous abortion (e.g. isotretinoin)
  • Intra-uterine growth restriction or 'IUGR' (e.g. beta-blockers)
  • Prematurity (e.g. statins)
  • Stillbirths (e.g. warfarin)
  • Obstetric complications (e.g. NSAIDs can cause excessive maternal bleeding used near term)
  • Neonatal side effects (e.g. CNS depression due to sedatives)
  • Withdrawal reactions in the neonate (e.g. opioid or benzodiazepine withdrawal)
  • Impaired neurodevelopment (e.g. sodium valproate)
  • Cancer (e.g. cervical adenocarcinoma caused by diethylstilbestrol)