Liver enzyme alterations during pregnancy in IBD are not attributable to disease activity or medication

BACKGROUND: Inflammatory bowel disease (IBD) is often diagnosed during reproductive age, requiring adequate management during pregnancy. Physiological changes during pregnancy affect liver enzymes, complicating interpretation in a population prone to liver test abnormalities. This study aims to investigate liver enzyme trends throughout pregnancy in women with IBD. METHODS: A retrospective cohort study was conducted in three Dutch university hospitals. Pregnant women with IBD were included; liver enzyme levels were analyzed throughout pregnancy using Bayesian modeling. The association between liver enzymes and IBD disease activity, medication, pregnancy and adverse pregnancy outcomes was assessed, with estimated marginal means (EMMs) reported across trimesters and clinical subgroups. RESULTS: Liver enzyme levels exhibited significant trimester-specific variations in pregnant individuals with IBD. Levels of aminotransferases, γ-glutamyl transferase (γGT) and bilirubin generally declined, particularly in the second trimester, whereas alkaline phosphatase (ALP) levels increased markedly in the third trimester, mirroring physiological changes observed in healthy pregnancies. Adverse pregnancy outcomes were not associated with differences in liver enzyme levels. Several medications - particularly ustekinumab, vedolizumab, thiopurines, corticosteroids and amino salicylates - were associated with liver enzyme values or interacted with pregnancy, modulating the direction or magnitude of change. However, these effects were generally modest and remained within reference values. CONCLUSIONS: In pregnant women with IBD, changes in liver enzyme levels reflect physiological gestational adaptations rather than pharmacologic effects. Although medication-specific interactions were detected, their clinical significance appears limited. Marked elevations in liver enzymes during pregnancy cannot routinely be attributed to IBD activity or medication and warrant urgent analysis.