Pregnancy: Potential harm

Last updated: Sunday, July 12, 2015

A drug does not need to cross the placenta to cause fetal toxicity. For example, any drug that causes vasoconstriction of the placental vasculature can harm the fetus. 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).

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Although fetal 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 retardation or 'IUGR' (e.g. many street drugs have been associated with IUGR although other factors may be responsible)

  • Prematurity (e.g. warfarin)

  • Stillbirths (e.g. warfarin)

  • Obstetric complications (e.g. NSAIDs can cause excessive maternal bleeding)

  • 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. phenytoin, sodium valproate)

  • Cancer (e.g. cervical adenocarcinoma caused by stilboestrol)