Serious Infections in Offspring Exposed to Tumour Necrosis Factor Inhibitors During Pregnancy: Comparison of Timing During Pregnancy and Placental Transfer Ability

Objective We evaluated serious infection risk in offspring exposed to tumour necrosis factor inhibitors (TNFi) in utero, separated by TNFi timing and placental transfer ability. Methods Using MarketScan (2011‐2021), we identified offspring born to mothers with chronic inflammatory diseases. TNFi exposure was defined as ≥1 filled prescription during pregnancy, further subdivided by trimesters and placental transfer. The event of interest was the time to first hospitalization with infection in the offspring's first year of life. We estimated associations between TNFi exposure and infection risk using multivariable Cox proportional hazards models, adjusting for maternal demographics, disease type, comorbidities, pregnancy complications, and drug exposure. Results We identified 56,866 offspring; 3,711 (6.5%) were exposed to TNFi during pregnancy. Overall, the association of TNFi exposure with the risk of serious infections versus unexposed offspring was not statistically significant (hazard ratio, HR, 0.85; 95% confidence interval, CI, 0.68, 1.07). However, offspring exposed during the third trimester had a 70% higher risk of serious infections than those exposed only in the first and/or second trimesters (HR 1.70; 95% CI 0.96, 01). Additionally, we observed an increased risk with exposure to any TNFi with higher placental transfer ability (infliximab, adalimumab, golimumab) overall (HR 1.49; 95% CI 0.83, 2.69) and during the third trimester (HR 1.30, 95% 0.65, 2.61), compared to only low placental transfer TNFi (certolizumab, etanercept), though both HR were not statistically significant. Conclusion Overall, TNFi exposure was not associated with serious infections; exploratory signals by timing and placental transfer were imprecise and require confirmation.