Background: Evidence suggests that pregnant women are disproportionally and more severely affected by infections. As pregnancy already leads to a decreased immune response, using tumour necrosis factor inhibitors (TNFi) during pregnancy could further impede the immune response and increase risk of serious infections. Pregnant women are commonly excluded from clinical trials and the main studies on serious infections occurring in pregnant women with chronic inflammatory diseases do not specifically focus on TNFi and/or fail to assess the postpartum period, which is a critical flaw, as women with chronic inflammatory diseases have a higher rate of caesarean delivery, which itself is associated with infectious complications.

Objectives: We assessed risk of hospitalized infection during the gestational and postpartum periods in mothers exposed to TNFi compared to unexposed mothers with chronic inflammatory diseases.

Methods: Using MarketScan (2011-2021), an administrative health database from the United States, we created a real-world cohort of pregnant women with a chronic inflammatory disease for which TNFi are routinely indicated (i.e. rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, psoriasis, and/or inflammatory bowel disease). The use of TNFi (i.e. adalimumab, certolizumab, etanercept, golimumab, infliximab) during gestation (i.e. onset of gestation until delivery) and postpartum (i.e. delivery until 90 days postpartum) was modelled as a time-varying variable and compared to no use. Cox proportional hazards models with frailties were used to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CI) associated with TNFi and hospital admissions for infections as the primary diagnosis. In these models, we controlled for maternal age, comorbidities, and drug use. In the multivariable analysis pertaining to the postpartum, we further adjusted for preterm birth and serious infections during pregnancy.

Results: We identified 62,813 women with chronic inflammatory disease, contributing 70,529 pregnancies and 51,320 person-years of follow-up during the gestational period. Overall, 4,485 (6.4%) pregnancies were exposed to at least one prescription for TNFi during the gestational period. During this period, 449 women were hospitalized for a serious infection, of which 418 (93.1%) had no use of TNFi, and 31 (6.9%) were TNFi users (Table 1). Compared with non-exposure, TNFi was associated with an increased risk of hospitalizations for infection (aHR 1.49; 95% CI 1.01, 2.19) during pregnancy. A total of 69,412 pregnancies resulted in a delivery, contributing to 16,266 person-years of follow-up during the 90-day postpartum period. A total of 3,559 (4.8%) of those deliveries were in women exposed to TNFi during the postpartum period. During this postpartum period, 205 women were hospitalized for infection, of which 17 (8.3%) were TNFi users, and 188 (91.7%) had no TNFi use. TNFi during postpartum was associated with an overall increased risk of serious infections during this period compared to non-TNFi users (aHR 1.68; 95% CI 1.01, 2.81). The most common infections in those exposed to TNFi were urinary tract during gestation and viral/systemic infections in postpartum. The most frequent infection for those unexposed to TNFi were viral/systemic in gestation and soft tissue infections in postpartum.

Conclusion: In the largest real-world study to date, women on TNFi had roughly a 50% and 70% higher risk of serious infections during gestation and postpartum, respectively. Our findings should prompt initiatives to minimize infectious complications during pregnancy and postpartum.

REFERENCES: NIL.

Acknowledgements: This research was funded by the Canadian Institutes of Health Research (CIHR) project grant awarded to EV. LKF is supported by a CIHR Canada Graduate Scholarships Doctoral Award. EV is supported by a salary support award from the Arthritis Society.

Disclosure of Interests: None declared.