Which corticosteroids do not cross the placenta?

Corticosteroids That Do Not Cross the Placenta

Prednisolone and prednisone are the preferred corticosteroids during pregnancy as they are largely metabolized by the placenta before reaching the fetus, with approximately 90% inactivation by placental 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) enzyme. 1, 2

Placental Transfer of Different Corticosteroids

Non-Fluorinated Corticosteroids (Limited Placental Transfer)

• Prednisolone/Prednisone:

  • Cross the placenta at only about 10% of maternal concentration 2
  • Placental 11β-HSD2 enzyme converts active prednisolone to inactive prednisone 3
  • Fetal prednisolone levels are approximately 10-fold lower than maternal levels 2
  • Strongly recommended for use during pregnancy when corticosteroids are needed 1

• Hydrocortisone:

  • Similar to prednisolone, metabolized by placental 11β-HSD2 1
  • May be substituted for prednisolone when parenteral administration is needed 1

Fluorinated Corticosteroids (Significant Placental Transfer)

• Dexamethasone and Betamethasone:

  • Readily cross the placenta with minimal inactivation 1, 4
  • Not inactivated by placental 11β-HSD2 enzyme 1
  • Used specifically when fetal exposure is desired (e.g., fetal lung maturation) 1
  • Should be avoided for maternal disease treatment during pregnancy 1
  • Repeated doses associated with neurocognitive and neurosensory disorders in offspring 1

• Budesonide and Fluticasone:

  • Research shows placental 11β-HSD2 does not metabolize these inhaled steroids 5
  • However, at usual inhaled doses, they have not been associated with increased risk of major malformations 1

Clinical Recommendations for Corticosteroid Use in Pregnancy

For Maternal Disease Treatment

• First Choice: Prednisolone or prednisone at lowest effective dose

  • Taper to <20 mg daily if possible, adding pregnancy-compatible steroid-sparing agents if necessary 1
  • Low-dose treatment (≤10 mg daily) can be continued throughout pregnancy if clinically indicated 1

• For Inhaled Corticosteroids:

  • Generally considered safe at usual doses 1
  • Budesonide and beclomethasone have more safety data during pregnancy and are preferred 1

Important Considerations

• Monitor for maternal complications:

  • Screen for gestational diabetes with glucocorticoid treatment 1
  • Consider adrenal suppression risk with >5 mg prednisolone daily for >3 weeks 1
  • May need increased glucocorticoid dose during delivery or with intercurrent illness 1

• Neonatal considerations:

  • With prolonged high-dose treatment, consider potential for neonatal adrenal insufficiency 1
  • With high doses, delay breastfeeding for 3-4 hours after dose to minimize transfer to breast milk 1

Summary

When treating maternal conditions during pregnancy, prednisolone and prednisone are the preferred corticosteroids due to their limited placental transfer. Fluorinated corticosteroids (dexamethasone and betamethasone) should be reserved for situations where fetal exposure is specifically desired, such as promoting fetal lung maturity in threatened preterm birth.