Do high-dose corticosteroids (steroids) during pregnancy cause fetal anomalies?

From the Guidelines

High-dose steroids during pregnancy do not significantly increase the risk of major fetal anomalies, and their use is considered relatively safe when medically necessary. According to the most recent study 1, corticosteroids like prednisone, prednisolone, and methylprednisolone are associated with a low risk of congenital abnormalities, with some studies suggesting a small increased risk of cleft palate with first-trimester exposure to high doses. However, this risk is not supported by more recent studies, and the benefits of steroid use in pregnancy typically outweigh the potential risks.

Key Points to Consider

• The lowest effective dose of steroids should be used during pregnancy to minimize potential risks 1.
• Patients should be monitored for maternal complications like gestational diabetes, hypertension, and preeclampsia, which can occur with prolonged steroid use 1.
• Some steroids, like betamethasone and dexamethasone, are specifically used to promote fetal lung maturity when preterm delivery is anticipated, demonstrating that controlled steroid use can benefit fetal development in specific circumstances.

Important Considerations

• The safety profile of azathioprine is excellent, and it is considered a safe option during pregnancy 1.
• Cyclosporine and tacrolimus are also considered safe during pregnancy, with no significant malformation risk associated with their use 1.
• Mycophenolate mofetil (MMF) is contraindicated in pregnancy due to its high risk of miscarriage, stillbirth, and structural anomalies 1.

From the FDA Drug Label

Corticosteroids have been shown to be teratogenic in many species when given in doses equivalent to the human dose Animal studies in which corticosteroids have been given to pregnant mice, rats, and rabbits have yielded an increased incidence of cleft palate in the offspring. Pregnancy Category C Corticosteroids should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus

High-dose steroid use in pregnancy may cause fetal anomalies, such as cleft palate, as seen in animal studies.

• The FDA drug label indicates that corticosteroids are teratogenic in many species.
• Pregnancy Category C implies that the potential benefit of corticosteroid use during pregnancy must be weighed against the potential risk to the fetus.
• The label advises careful observation of infants born to mothers who have received substantial doses of corticosteroids during pregnancy for signs of hypoadrenalism 2.

From the Research

High Dose Steroid Use in Pregnancy

• The use of high-dose steroids in pregnancy has been associated with potential risks to the fetus, including fetal anomalies 3.
• However, studies have shown that low to moderate doses of corticosteroids are safe throughout pregnancy 4, 5.
• High-dose prednisone is reserved for severe lupus complications but is associated with significant pregnancy-related complications and poor obstetrical outcomes 3.
• The pharmacokinetics of corticosteroids change during pregnancy, but systemic corticosteroids are not teratogenic 5.

Fetal Anomaly Risk

• There is no clear evidence that high-dose steroid use in pregnancy causes fetal anomalies, but it may increase the risk of premature rupture of amniotic membranes and low birthweight babies 5.
• A study on azathioprine use during pregnancy in systemic lupus erythematosus patients found no association with poor fetal outcome, including congenital malformations 6.
• Another study suggested that azathioprine, cyclosporine, hydroxychloroquine, and steroids are relatively safe during pregnancy, whereas methotrexate, cyclophosphamide, mycophenolate mofetil, and leflunomide are contraindicated 7.

Safety Considerations

• When prescribing immunosuppression medication to pregnant women, it is essential to consider the potential risks and benefits, as well as the lack of controlled trials on the safety of these medications 7.
• Prospective registries and outcome studies on the offspring are necessary to answer questions about the incidence of fetal malformations and long-term safety 7.