Background/Purpose: Tumor Necrosis Factor inhibitors (TNFi) are increasingly used during RA pregnancy. Most of these are actively transported across the placenta, reaching higher fetal than maternal blood levels. Despite concerns that these drugs cause immunosuppression, there are no data on the risk of serious infections in exposed offspring. Thus, we evaluated serious infections in RA offspring exposed to TNFi in the preconception and/or gestational period compared to unexposed RA offspring, as well as to children from the general population.

Methods: The “PregnAncies in RA mothers and Outcomes in offspring in the United States cohort (PAROUS)” includes all women with ≥1 hospitalization for delivery after RA diagnosis, identified through MarketScan commercial databases (2011-2014). PAROUS also includes a randomly selected control group of women, matched ≥4:1 for age, year of delivery, and state of residence, without an RA diagnosis prior to or at the time of delivery. Only women continuously enrolled within MarketScan for ≥12 months prior to delivery and with available child linkage were included in PAROUS. We identified children born live to RA mothers and their matched controls, and defined TNFi exposure based on ≥1 filled prescription of adalimumab, certolizumab, etanercept, golimumab, or infliximab during pregnancy and/or the preconception period (ie 12 weeks prior to conception). We ascertained serious infections based on ≥1 hospitalization with infection as a primary diagnosis, ≤12 months of life. We performed multivariate analyses with generalized estimating equations to adjust for maternal demographics, co-morbidities, pregnancy complications, and drugs.

Results: We identified 2455 RA offspring and 11 018 matched controls. Among children born to RA women, 290 (11.8%) were exposed to TNFi during pregnancy (ie TNFi pregnancy) (including 109 in the third trimester), 109 (4.4%) were unexposed during pregnancy but exposed in the preconception period (ie TNFi preconception), and 2056 (83.7%) were unexposed both during the pregnancy and preconception periods (ie RA with no TNFi). Each group of RA offspring experienced more serious infections vs general population controls [TNFi pregnancy 3.1% (95%CI 1.5,6.0), TNFi third trimester 2.8% (95%CI 0.7,8.4), TNFi preconception 1.8% (95%CI 0.5,6.4), RA with no TNFi 2.1% (95%CI 1.6,2.9), vs controls 0.2% (95%CI 0.1,0.2)]. In multivariate analyses, children born to RA women had a substantially increased risk of serious infections vs controls [OR for TNFi pregnancy 15.4 (95%CI 6.2,38.6), OR for TNFi preconception 9.6 (95%CI 2.1,43.8), OR for RA with no TNFi 12.8 (95%CI 6.9,23.8)]. We were unable to establish an increased risk of serious infections in RA offspring exposed to TNFi during pregnancy compared to unexposed RA offspring (OR 1.2; 95%CI 0.6,2.6); results were similar when we restricted TNFi exposure to the third trimester (OR 1.0; 95%CI 0.3,3.4).

Conclusion: Compared to children from the general population, children born to RA women have a substantially increased risk of serious infections. We were unable to establish a marked excess risk for serious infections in RA offspring exposed to TNFi during pregnancy, including the third trimester, vs unexposed RA offspring.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/serious-infections-in-ra-offspring-exposed-to-tumor-necrosis-factor-inhibitors/