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Editorial: severe outcomes are rare in pregnancy with autoimmune hepatitis

In a recent issue of AP&T, Grønbaek et al examine the association between pregnancy and birth outcomes in women with autoimmune hepatitis using Danish population‐based registers. It is an interesting paper confirming previous population‐based data from Sweden with regard to not only preterm birth, but also offering new insights into miscarriages and fertility among women with autoimmune hepatitis. Although records may not be complete (the Grønbaek et al study was restricted to hospital‐recorded events and could not capture early miscarriages), there were still 28 miscarriages in 721 pre‐menopausal women with autoimmune hepatitis. This number did not constitute an excess risk (odds ratio = 1.17; 95% CI: 0.81‐1.68), which is comforting to patients, families and physicians. None of the 70 women with autoimmune hepatitis in the Danish study had a record of stillbirth. Meanwhile Stokkeland et al reported a stillbirth rate of 1.2% (two of 171 infants) in women with autoimmune hepatitis. Add to this, that the Swedish study found no increase in neonatal mortality and it seems reasonable to conclude that autoimmune hepatitis is no major risk factor for “very severe” pregnancy/perinatal outcome. However, it is when we turn our eyes to “moderately severe” pregnancy outcome that we perceive the consequences of autoimmune hepatitis (as well as of other chronic liver diseases). The odds ratios for preterm birth for women with AIH compared to controls were almost identical in the Grønbaek et al and the Stokkeland et al studies (3.19 and 3.21 respectively). And it should be noted that most cases of preterm birth reflect moderate and not very preterm birth. Only 1 in 23 births to women with autoimmune hepatitis ended with a very preterm birth (<32 gestational weeks), even if this compares with 1 in 132 births to control women. As opposed to the Swedish study, Danish data indicate that autoimmune hepatitis may be a risk factor for small for gestational age. More data are obviously needed here given the conflicting results. We urge caution when interpreting null findings with regards to congenital malformations in autoimmune hepatitis. First, Grønbaek et al did not have access to data on malformations from other registers than the medical birth register and may therefore have missed a substantial proportion of malformations (for instance, heart birth defects are often found after birth). Second, their study had limited power to detect malformations (recent Swedish data suggest that only one in 67 children in the general population have a heart birth defects, and the Danish study only included 70 women with autoimmune hepatitis). Limited statistical power also means that a link between adverse pregnancy outcome in autoimmune hepatitis and immunosuppression and/or presence of concomitant cirrhosis cannot be ruled out. For that, larger studies are probably needed. Additional caveats include risk of misclassification bias as 13% of women did not have a liver biopsy, a requirement for the AIH diagnosis. Finally, women with concurrent liver diseases, including hepatitis C, were not excluded. With these limitations, the paper from Grønbaek et al nevertheless adds important insights using population‐based register data thereby avoiding the kind of selection bias from which tertiary centre studies may suffer.