Risk of Adverse Pregnancy Outcomes in Patients with Non-Communicable, Chronic Inflammatory Barrier Diseases Under Systemic Treatment: A Large-Scale Retrospective Cohort Study

Chronic inflammatory barrier diseases (CIBDs) affect many women of reproductive age, yet the safety of biologics during pregnancy remains inadequately investigated. This retrospective cohort study used the US Collaborative Network of TriNetX to evaluate the risk of adverse pregnancy outcomes (APOs) among women with CIBD receiving tumor necrosis factor inhibitors (TNFis), interleukin-23 inhibitors (IL-23is), or conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), compared with untreated CIBD controls and the general pregnant population. Among 1842 pregnant women with CIBD receiving systemic therapy, 1188 were exposed to TNFis, 170 to IL-23is, 370 to azathioprine (csDMARD), and 114 to methotrexate (MTX) (csDMARD). The incidence of any APO ranged from 11% in untreated CIBD controls to 19% with ustekinumab (IL-12/23i). Among treatment groups, rates were 17% with TNFis, 18% with IL-23is, 13% with azathioprine, and 15% with MTX, compared with 17% in the general pregnant population. APO rates were comparable between the overall TNFi group and the TNFi group excluding certolizumab pegol (CZP) (TNFi). In the only non-exploratory comparison, TNFi exposure was associated with higher risks of (pre-)eclampsia and hypertension but a lower risk of abortion or intrauterine death versus CIBD controls, with no significant difference for overall APO. No treatment group showed a markedly increased overall APO risk, supporting tailored decision-making that balances the consequences of uncontrolled maternal disease against individual treatment-associated risks.