Azathioprine Safety in First Trimester of Pregnancy for Takayasu Arteritis
Yes, azathioprine should be continued throughout the first trimester and entire pregnancy in a woman with Takayasu arteritis, as the risk of disease flare from discontinuation substantially outweighs any potential fetal risk. 1
Guideline-Based Recommendation for Continuation
The American College of Rheumatology (ACR) strongly recommends continuing azathioprine throughout pregnancy for rheumatic diseases, including Takayasu arteritis, as it is considered compatible with pregnancy. 1 This recommendation is based on extensive human cohort data from inflammatory bowel disease, lupus nephritis, and autoimmune hepatitis demonstrating relative safety despite the FDA category D classification. 2, 1
Critical Safety Evidence
Azathioprine appears to be a safe drug during pregnancy, although it is teratogenic in animals. Steadily increasing experience is being reported in women with autoimmune hepatitis, rheumatoid arthritis, inflammatory bowel diseases, and after organ transplantation. 2
Large cohort studies have linked azathioprine use to low birth weight and preterm birth but not to an increased rate of congenital malformations overall. 1 A Swedish registry study of 476 women found a trend toward increased malformations (6.2% vs 4.7%, adjusted OR 1.41,95% CI 0.98-2.04) that did not reach statistical significance, though a specific association with ventricular/atrial septal defects was observed (adjusted OR 3.18,95% CI 1.45-6.04). 3
Glucocorticoids, hydroxychloroquine, azathioprine, tacrolimus, and cyclosporine are considered safe immunosuppressive treatments during pregnancy. 2
Risk of Discontinuation vs. Continuation
Discontinuing or tapering azathioprine during pregnancy increases the risk of disease flare, which poses a greater threat to maternal and fetal health than continued therapy. 2, 1 In a small case series of 14 autoimmune hepatitis patients in whom immunosuppression was reduced during pregnancy, 12/14 patients had a rapid flare following delivery (or stillbirth in one patient). 2
For Takayasu arteritis specifically, prednisolone ± azathioprine for treatment should be continued during pregnancy to prevent disease flares, which might be more deleterious to pregnancy outcome than any potential risk of the medication. 2
Disease Activity Monitoring During Pregnancy
The ACR recommends assessing disease activity and inflammatory markers (ESR, CRP) at least once per trimester during pregnancy. 1
Vascular examination for new bruits or pulse deficits should be performed at each prenatal visit to detect new stenoses. 1
Four-extremity blood pressures should be obtained at every assessment. 1
Dosing and Management Strategy
Azathioprine dosing may be escalated up to 2 mg/kg/day if needed for disease control during pregnancy. 1 The typical maintenance dose is 1-2 mg/kg/day. 2
If disease flare occurs during pregnancy, the ACR advises increasing the prednisone dose (40-60 mg daily for active inflammation) rather than introducing additional immunosuppressants. 1
Medications to Avoid
Methotrexate, mycophenolate mofetil, leflunomide, and cyclophosphamide are contraindicated in pregnancy due to teratogenicity and must be discontinued before conception. 1 Mycophenolate formulations are particularly problematic and should be switched to azathioprine at least 6 weeks before planned conception. 2
Postpartum Considerations
The ACR notes a heightened risk of disease flare during the first 3-6 months after delivery; immunosuppression should not be tapered for at least three months postpartum. 1 Flares during pregnancy occurred in 21-33% of patients in various series, whereas 52% of patients had postpartum flares. 2
Conventional therapy must be resumed pre-emptively 2 weeks before anticipated delivery and maintained throughout the postpartum period to prevent exacerbation. 2
Breastfeeding Compatibility
Azathioprine, prednisone, and low-dose aspirin are all compatible with breastfeeding. 1 Although very little azathioprine is excreted in breast milk, azathioprine metabolites can be detected in breastmilk but have not been linked to adverse infant outcomes. 2, 1
Additional Pregnancy Management
Low-dose aspirin (75-162 mg daily) should be initiated in the first trimester to lower the risk of fetal loss, preeclampsia, and intra-uterine growth restriction in patients with inflammatory vascular disease. 2, 1
Hydroxychloroquine should be continued during pregnancy if the patient is taking it, as withdrawal has been associated with disease flare. 2
Common Pitfalls to Avoid
Do not discontinue azathioprine due to FDA category D classification alone—this rating reflects animal teratogenicity data, not human experience. The extensive human safety data supports continuation. 2, 1
Do not rely on inflammatory markers alone for disease activity assessment—they are elevated in only 50% of active Takayasu arteritis cases. Clinical assessment combined with vascular examination is essential. 1
Do not taper immunosuppression during pregnancy or early postpartum—this is the highest-risk period for disease flare. 2, 1
Do not switch from azathioprine to another agent during pregnancy if disease is well-controlled—medication changes introduce unnecessary risk. 1