Is it safe to prescribe systemic corticosteroids during pregnancy, and which agents, dosing regimens, and monitoring strategies are recommended?

Systemic Corticosteroids in Pregnancy: Safety, Agent Selection, and Management

Systemic corticosteroids are safe to use during pregnancy when clinically indicated, with prednisone and prednisolone preferred over dexamethasone or betamethasone for maternal conditions because they are extensively metabolized by the placenta, limiting fetal exposure to approximately 10% of the maternal dose. 1

Safety Profile and Teratogenicity Risk

Prednisone and prednisolone do not increase the risk of major birth defects, congenital malformations, or stillbirth when used for disease control in pregnant women. 1

• A large nationwide cohort study of nearly 52,000 pregnancies with first-trimester corticosteroid exposure showed no increased risk of congenital malformations, contradicting older literature that reported increased orofacial clefts. 1
• First-trimester use carries the greatest theoretical risk of teratogenicity, but recent large studies show no increased malformation risk. 1
• The European League Against Rheumatism states that first-trimester prednisone use for disease control is not associated with increased risk of major birth defects, stillbirth, preterm delivery, or congenital malformations. 1
• Hydrocortisone is classified as FDA pregnancy category B and has not been shown to be teratogenic in humans at therapeutic doses. 2

Preferred Corticosteroid Agents for Maternal Indications

Prednisone, prednisolone, and hydrocortisone are the preferred systemic corticosteroids for maternal conditions because placental 11-β-hydroxylase metabolizes them extensively, resulting in only 10% of the maternal dose reaching the fetus. 1, 2

• Dexamethasone and betamethasone cross the placenta more readily and should be reserved exclusively for fetal indications such as lung maturation, not for maternal disease control. 1, 2
• Betamethasone and dexamethasone are used to treat the fetus directly, not the mother. 3

Dose-Dependent Recommendations and Tapering Strategy

Start with 10-20 mg/day of prednisone for maternal disease control, then taper to the lowest effective dose, ideally ≤5 mg/day once disease stability is achieved. 1

• Daily doses ≤5 mg prednisone are associated with low risk. 1
• The American College of Rheumatology conditionally recommends continuing low-dose glucocorticoid treatment (≤10 mg daily) during pregnancy if clinically indicated. 1
• Doses >5 mg/day carry dose-related risks including gestational diabetes, pregnancy-associated osteoporosis, serious maternal infections, and preterm birth. 1
• The American College of Rheumatology strongly recommends tapering higher doses to <20 mg daily, adding pregnancy-compatible glucocorticoid-sparing agents (azathioprine, hydroxychloroquine, cyclosporine, tacrolimus) if necessary. 1

Timing Considerations Across Trimesters

After the first trimester, short bursts of corticosteroids may be used more liberally, especially if maternal disease poses greater risk than the medication. 4, 1

• First trimester use has the greatest theoretical risk of potential teratogenicity, though recent evidence is reassuring. 4
• Corticosteroids in short bursts may be safe after the first trimester, with use better justified in severe disease, especially if causing exacerbation of asthma. 4
• Avoid aggressive tapering in the final weeks before delivery, as rapid dose reduction may precipitate disease flare (e.g., thrombocytopenia). 1

Mandatory Monitoring During Pregnancy

Screen for gestational diabetes, particularly in women on glucocorticoid therapy, as corticosteroids cause hyperglycemia and can lead to or worsen diabetes. 4, 1

• Monitor blood pressure closely for hypertension and preeclampsia in women receiving prednisone. 1
• Increased surveillance for preeclampsia is warranted. 1
• Assess for excessive weight gain, steroid-induced psychosis, and osteoporosis as part of routine follow-up. 1
• Patients should undergo diabetes testing prior to use, especially if a longer course of corticosteroids is being considered. 4

Peripartum Stress-Dose Coverage

Women receiving oral steroids ≥7.5 mg daily for at least 2 weeks require stress-dose hydrocortisone intravenously during active labor and cesarean section to prevent maternal hypothalamic-pituitary-adrenal axis suppression. 1

• Women taking >5 mg prednisolone daily for more than 3 weeks are at increased risk of adrenal suppression and require consideration of increased glucocorticoid dosing at delivery, and during intercurrent infection, vomiting, or hyperemesis gravidarum. 1
• During delivery, 100 mg hydrocortisone should be administered intravenously at the onset of active labor, followed by either continuous infusion of 200 mg/24 hours or 50 mg intramuscularly every 6 hours. 2
• After uncomplicated delivery, rapid tapering over 1-3 days to the regular replacement dose is appropriate. 2

Intranasal Corticosteroids for Rhinosinusitis

All modern intranasal corticosteroids including budesonide, fluticasone propionate, fluticasone furoate, and mometasone are safe at recommended doses during pregnancy. 4, 5

• The European Respiratory Society recommends that inhaled corticosteroids, including fluticasone, are not associated with increased risk of major congenital malformations, intrauterine growth restriction, preterm delivery, or low birth weight at usual therapeutic doses. 5
• A meta-analysis confirmed that intranasal corticosteroids during pregnancy do not increase risks of major malformations, preterm delivery, low birth weight, or pregnancy-induced hypertension. 5
• The off-label use of budesonide irrigations or corticosteroid nasal drops is not recommended. 4

Breastfeeding Compatibility

Prednisone and hydrocortisone are compatible with breastfeeding; low-dose therapy results in minimal drug transfer into breast milk. 1, 2

• The American Academy of Pediatrics considers oral steroids to be compatible with breastfeeding. 4
• For prolonged high-dose maternal therapy, delaying breastfeeding by 3-4 hours after the dose reduces infant exposure. 1, 2
• Hydrocortisone is excreted minimally into breast milk, and breastfeeding by women on low-dose therapy is generally considered safe. 2

Critical Pitfalls to Avoid

Do not withhold necessary prednisone therapy due to pregnancy concerns—uncontrolled maternal disease poses greater risk to both mother and fetus than appropriate prednisone use. 1

• Consultation with the patient's obstetrician is recommended when using corticosteroids, particularly for conditions less severe than life-threatening disease. 4, 1
• Do not confuse prednisone with mycophenolic acid (MPA) products, which are absolutely contraindicated in pregnancy due to high risk of congenital malformations. 1
• Dexamethasone or betamethasone should not be used for maternal conditions, as these cross the placenta more readily and are intended for fetal treatment. 2
• If high-dose prednisone is continued up to birth, the newborn should be monitored for adrenal insufficiency. 1
• Neonatal hypoglycemia has been reported after antenatal betamethasone administration, especially in preterm, low birth weight infants, and when administered close to the time of delivery. 6

Alternative Therapy When Corticosteroids Fail

When prednisone is ineffective or causes significant adverse effects, intravenous immunoglobulin (IVIg) should be considered as an alternative therapeutic option. 1

• Combining pregnancy-compatible immunosuppressive agents (azathioprine, hydroxychloroquine, cyclosporine, tacrolimus) may allow for glucocorticoid dose reduction. 1