What is the comparative teratogenicity of prednisolone (corticosteroid) and dexamethasone (corticosteroid) during pregnancy?

Prednisolone is Preferred Over Dexamethasone During Pregnancy Due to Lower Teratogenic Risk

Prednisolone should be used instead of dexamethasone during pregnancy when corticosteroid therapy is required for maternal conditions, as it has a lower teratogenic risk due to reduced placental transfer. 1

Comparative Teratogenicity of Prednisolone vs. Dexamethasone

Placental Transfer

• Prednisolone/Prednisone: Only about 10% of maternal dose crosses the placenta to reach the fetus 1
• Dexamethasone: Crosses the placenta more readily as it is not well metabolized by the placenta, resulting in higher fetal exposure 1

Safety Profile

• Prednisolone: Not associated with increased rate of major birth defects and can be safely used during pregnancy if needed to control active disease 1
• Dexamethasone: Specifically used for fetal conditions (e.g., lung maturity) precisely because it reaches the fetus in higher concentrations 1
• FDA Classification: Prednisolone is classified as Category B (no evidence of risk in humans), while dexamethasone carries Category C classification (risk cannot be ruled out) 2, 3

Clinical Recommendations for Corticosteroid Use in Pregnancy

Dosing Guidelines

• Taper prednisolone when possible to ≤5 mg/day maintenance dose during pregnancy 1
• Daily doses ≤5 mg of prednisolone are associated with low risk of maternal-fetal complications 1
• Higher doses should be weighed against potential risks including:
  • Pregnancy-associated osteoporosis
  • Gestational diabetes
  • Serious maternal infections
  • Preterm birth 1

Disease-Specific Considerations

• For immune thrombocytopenia: Low-dose prednisolone (10-20 mg/day) is recommended as first-line treatment, adjusted to minimum effective dose 1
• For rheumatic diseases: Prednisolone is preferred over dexamethasone for maternal conditions 1
• For severe, refractory maternal disease: IV methylprednisolone pulses may be considered 1

Potential Adverse Effects of Corticosteroids in Pregnancy

Maternal Risks

• Hypertension and preeclampsia
• Hyperglycemia/gestational diabetes
• Premature rupture of membranes 4

Fetal Risks

• Conflicting data regarding birth defects:
  • Some studies show no increased risk 1
  • Others indicate potential 3-fold increased risk of isolated cleft lip/palate with first trimester exposure 1, 4
• High doses have been associated with low birth weights 1

Breastfeeding Considerations

• Prednisolone is excreted minimally into breast milk 1
• Breastfeeding by women on low-dose prednisolone therapy is generally considered safe 1
• To minimize infant exposure, breastfeeding can be avoided during the first 4 hours after prednisolone intake 1

Common Pitfalls and Caveats

1. Avoid dexamethasone for maternal conditions: Reserve dexamethasone for specific fetal indications like lung maturation
2. Don't abruptly discontinue: Tapering is essential to prevent adrenal insufficiency
3. Monitor closely: Women on corticosteroids during pregnancy need close monitoring for diabetes, hypertension, and infections
4. Consider lowest effective dose: Always use the minimum dose required to control disease activity

When corticosteroid therapy is required during pregnancy, prednisolone should be the first choice for maternal conditions due to its reduced placental transfer and established safety profile, while dexamethasone should be reserved for specific fetal indications.