Introduction: Thiopurines, including azathioprine (AZA), are commonly used immunosuppressants in pregnant women with chronic kidney disease (CKD). While generally considered safe, studies in inflammatory bowel disease populations have suggested possible associations with intrahepatic cholestasis of pregnancy (ICP) and altered thiopurine metabolism during pregnancy. Evidence in CKD populations remains limited.
Methods: A retrospective single-centre cohort study of pregnant women exposed to thiopurines at the Royal Women’s Hospital (RWH) was conducted (2020–2025). Maternal, renal, neonatal outcomes, and thiopurine metabolite data were extracted from electronic medical records. Associations were analysed using Fisher’s exact and Wilcoxon rank-sum tests.
Results: 32 pregnancies in 30 women were included. No disease flares or transplant rejection were observed. ICP occurred in 6/31 (19.4%) pregnancies and was associated with preterm birth (p = 0.021). 5/6 (83.3%) ICP cases were severe. 6-TGN levels remained relatively stable during pregnancy, while 6-MMP levels and 6-MMP/6-TGN ratios demonstrated greater variability across pregnancy. Pregnancies complicated by ICP demonstrated numerically higher metabolite ratios and frequent metabolite shunting (75%). Cytopenia occurred in 6/15 (40%) neonates with available data and was transient in all cases.
Conclusion: Thiopurines appeared generally safe in pregnancy. However, increased thiopurine metabolite shunting during pregnancy may be associated with severe ICP and subsequent preterm birth. Transient neonatal cytopenia was relatively common, although the underlying cause is uncertain. Associations between thiopurine metabolite levels and adverse pregnancy outcomes in CKD cohorts warrant further investigation in larger prospective studies.