In the Hopkins Lupus Cohort, 31 pregnancies were exposed to azathioprine.20 There was no increase in the rate of miscarriages for pregnancies exposed to azathioprine in the first 20 weeks of pregnancy. The risk of stillbirth was increased in pregnancies with azathioprine, however this appeared to be related to higher lupus activity among women taking the medication. Among the 18 women who conceived while taking azathioprine, two of the four that developed highly active lupus in pregnancy suffered a loss. Another two of the four that discontinued the drug suffered a loss. The remaining 10 pregnancies in which the woman continued the drug and maintained low activity lupus resulted in live births. I recommend continuing azathioprine during pregnancy if it was required prior to conception to treat SLE. Based on the current evidence, the risk of discontinuation prompting a significant flare may outweigh the toxicity to the fetus.
Corticosteroids can be used in pregnancy when needed, though prophylactic treatment is not recommended. Routine use of corticosteroids may increase the risk for hypertension, diabetes, infection, and preterm birth. Moderate doses of corticosteroids to treat active lupus, however, are well tolerated. Prednisone and prednisolone are metabolized by the placenta, allowing only 10% of the maternal dose to reach the fetus. Fluorinated corticosteroids, such as dexamethasone and betamethasone, are not metabolized and thus easily transfer to the fetus. Therefore, fluorinated steroids can be used to treat the fetus, such as to modify congenital heart block or prior to a preterm delivery, but they should be avoided in routine treatment of lupus during pregnancy. Corticosteroid use in the first trimester has been associated with a three-fold increased risk for cleft lip and palate.21 The absolute risk for this complication is low, occurring in an average of three per 1,000 live births with early corticosteroid exposure. Lip and palate formation are complete by the eighth week of gestation, so steroid use later in pregnancy may not increase this risk.
Medications not considered safe in pregnancy include cyclophosphamide, mycophenolate mofetil, methotrexate, and leflunomide.19 Each of these drugs has been clearly associated with congenital anomalies, particularly when exposure occurs in the first trimester. If a woman contemplating pregnancy is taking one of these medications, it should be discontinued if possible and replaced with azathioprine, sulfasalazine, or a moderate dose of prednisone. If pregnancy occurs while the patient is taking one of these drugs, close obstetrical follow-up is required. The rate of congenital abnormalities does not dictate routine pregnancy termination, but fetuses should be examined closely for abnormalities via ultrasound. Women on leflunomide should be treated with cholestyramine to eliminate the drug if pregnancy is desired or discovered.
