Reply

We would like to thank Efe et al. for their interest in our review article. [1] The authors referenced the Pregnancy Inflammatory bowel disease And Neonatal Outcomes registry data that demonstrated adverse pregnancy outcomes with corticosteroid exposure in patients with inflammatory bowel disease (IBD). [2] Corticosteroid use in IBD is associated with disease activity (DA), and doses are typically higher than maintenance dose used with autoimmune hepatitis (AIH). In the IBD cohort, it is difficult to differentiate the impact of DA versus corticosteroid use on pregnancy related outcomes. Data from systemic lupus erythematosus (SLE) pregnancies show the mean dose of corticosteroids greater than 6.5 and 10 mg per day is associated with an adverse outcome and preterm birth (PTB) respectively. [3] However, these adverse outcomes in SLE pregnancies were also associated with increased DA. This highlights the importance of maintaining inflammatory conditions in remission at conception and avoid flares necessitating the use of high dose corticosteroids during pregnancy. Data from the Danish and Swedish registry study of pregnancy outcomes in rheumatoid arthritis (RA) suggest that the DA may be the most significant risk factor for PTB and small for gestational age (SGA) compared with immunosuppression use including corticosteroids. [4] When 1739 pregnancies with RA were compared with 17,390 agematched population controls, RA pregnancies with high DA had increased risk for PTB and even more so for SGA. Corticosteroid use in RA pregnancies showed significantly increased risk of PTB (adjusted odds ratio [aOR], 2.62; 95% confidence interval [CI], 1.23– 5.59). However, when adjusted for DA, the risk was not statistically significant (aOR, 2.11; 95% CI, 0.94– 4.74). The outcome associated with corticosteroid use may be a reflection of severe DA. A recent metaanalysis of AIH pregnancy outcomes showed no significant difference in fetal loss or PTB between patients receiving corticosteroid monotherapy and patients receiving corticosteroids with azathioprine. [5] This supports the use of azathioprine in AIH pregnancy in addition to more expansive data from IBD and rheumatology cohorts. The same metaanalysis demonstrated lower DA and risk of biochemical flare intrapartum compared to postpartum (relative risk, 0.31; p < 0.00001) except in those with portal hypertension who had increased risk of intrapartum loss of biochemical remission (LOBR). [5] Interestingly, stable disease at conception was associated with fewer postpartum LOBR and PTB. Preconception counseling would be the ideal opportunity to optimize DA before conception and manage patients with high risk with significant portal hypertension. Overall, patients with AIH, especially those of childbearing age, should aim for steroidsparing immunosuppression to achieve stable disease ideally before conception. Once pregnancy is achieved, it would be reasonable to use the lowest corticosteroid dose to maintain biochemical remission (BR). Despite the increased risk in LOBR postpartum, not all patients will lose BR and preemptively increasing immunosuppression in all patients is not recommended. We endorse close monitoring 8– 12 weeks postpartum for LOBR that can be effectively managed with augmentation of immunosuppression. To conclude, achieving stable disease at conception and risk stratification of individuals’ risk through preconception counseling would benefit patients with AIH and achieve the best pregnancy related outcomes.