What are the guidelines for using prednisone (corticosteroid) during pregnancy?

Prednisone Use in Pregnancy

Prednisone can be safely used during pregnancy when clinically indicated, with low doses (≤10 mg/day) recommended for maintenance therapy, while higher doses should be tapered to <20 mg/day with addition of steroid-sparing agents when possible. 1

Dosing Guidelines

Low-dose therapy (≤10 mg/day prednisone or equivalent) can be continued throughout pregnancy if clinically indicated. 1 This represents a conditional recommendation from the American College of Rheumatology based on the balance between disease control and minimal fetal exposure.

Higher doses must be tapered to <20 mg/day, adding pregnancy-compatible glucocorticoid-sparing agents (such as azathioprine, hydroxychloroquine, or calcineurin inhibitors) if necessary to maintain disease control. 1 This is a strong recommendation reflecting the dose-dependent risks of prolonged high-dose therapy.

Safety Profile and Fetal Considerations

• Only 10% of maternal corticosteroid dose reaches the developing fetus because prednisone and prednisolone are metabolized by placental 11β-hydroxysteroid dehydrogenase type 2. 1

• Older concerns about cleft lip/palate with first-trimester use have not been supported by recent studies. 1 The FDA label notes animal studies showed increased cleft palate, but this is not consistently demonstrated in human pregnancy. 2

• Prednisone is not associated with increased major birth defects when used at appropriate doses. 3, 4, 5 Clinical experience spanning decades supports safety for usual therapeutic doses.

Maternal Risks Requiring Monitoring

Women taking >5 mg prednisolone daily for more than 3 weeks are at increased risk of adrenal suppression and require consideration of stress-dose glucocorticoids at delivery, particularly for cesarean section. 1 The American College of Rheumatology conditionally recommends against routine stress dosing for vaginal delivery but conditionally recommends it for surgical delivery. 1

Screen all women on glucocorticoid therapy for gestational diabetes mellitus as this is a dose-dependent complication. 1

Higher doses (>5 mg/day) carry dose-related risks including:

• Gestational diabetes 1, 3
• Pregnancy-associated osteoporosis 3
• Serious maternal infections 3
• Preterm birth 3, 6
• Premature rupture of membranes 4

Research demonstrates that higher prednisone dose trajectories are associated with reduced gestational age, with the highest versus lowest dose groups showing 2.3-2.6 weeks shorter gestation. 6

Clinical Management Algorithm

Step 1: Assess disease activity and current prednisone dose

• If disease is stable on ≤10 mg/day: Continue current dose 1
• If on >10 mg/day: Proceed to Step 2

Step 2: For doses >10 mg/day, initiate dose reduction strategy

• Target dose <20 mg/day (strong recommendation) 1
• Add pregnancy-compatible steroid-sparing agent (azathioprine, hydroxychloroquine, tacrolimus, or cyclosporine) 1
• Monitor disease activity during taper

Step 3: Implement pregnancy-specific monitoring

• Screen for gestational diabetes (all patients on glucocorticoids) 1
• Monitor blood pressure for preeclampsia risk 1
• Assess for adrenal suppression if dose >5 mg/day for >3 weeks 1

Step 4: Plan delivery management

• For vaginal delivery: Routine stress dosing not recommended 1
• For cesarean delivery: Administer stress-dose glucocorticoids 1
• Consider stress dosing for hyperemesis gravidarum or intercurrent infection 1

Important Caveats

Use nonfluorinated glucocorticoids (prednisone, prednisolone, methylprednisolone) rather than fluorinated forms (betamethasone, dexamethasone) during pregnancy unless fetal treatment is specifically intended, as fluorinated forms cross the placenta more readily. 1

Prednisone exhibits dose- and concentration-dependent pharmacokinetics during pregnancy, with apparent oral clearance increasing from 35.1 L/h at 5 mg to 64.3 L/h at 20 mg doses. 7 This may necessitate dose adjustments to maintain therapeutic effect.

The primary goal is maintaining maternal disease control, as active maternal disease poses greater risks to pregnancy outcomes than appropriate glucocorticoid therapy. 1, 4, 5 Uncontrolled disease increases risks of preterm delivery, preeclampsia, and fetal loss.

Breastfeeding Considerations

Prednisone is compatible with breastfeeding as minimal amounts transfer to breast milk. 4, 5 Breast milk/plasma ratios are 0.5-0.6 for prednisone and 0.02-0.03 for prednisolone, with relative infant doses of only 0.35-0.53% and 0.09-0.18% respectively. 7