TOPLINE:

In utero exposure to TNF inhibitors among offspring born to mothers with chronic inflammatory diseases was not associated with an increased risk for serious infections. However, among those exposed to TNF inhibitors, third‑trimester exposure or exposure to high-placental-transfer inhibitors was associated with a nonsignificantly increased risk for serious infections during the first year of life.

METHODOLOGY:

• Researchers conducted a retrospective population-based cohort study to assess whether in utero exposure to TNF inhibitors — categorized by timing and by placental-transfer potential — was associated with an increased risk for serious infections in offspring after birth.
• They analyzed data of 56,866 offspring born to mothers with chronic inflammatory diseases such as inflammatory bowel disease, rheumatoid arthritis, psoriatic arthritis, or psoriasis.
• In utero exposure to TNF inhibitors was defined as the mother having at least one filled prescription or claim for an infusion procedure during pregnancy; 3711 exposed offspring were compared with 53,155 unexposed offspring.
• The timing of exposure was classified by trimester, and TNF inhibitors were stratified into two groups based on placental-transfer potential: high (infliximab, adalimumab, or golimumab) and low (certolizumab pegol or etanercept).
• The primary outcome measure was the time to first serious infection occurring in the offspring within the first 12 months of life; maternal demographics, disease type, comorbidities, pregnancy complications, and drug exposure were adjusted for in the analysis.

TAKEAWAY:

• Overall, exposure vs nonexposure to TNF inhibitors during pregnancy showed no statistically significant association with the risk for serious infections (adjusted hazard ratio [aHR], 0.85; 95% CI, 0.68-1.07).
• Offspring exposed during the third trimester had an estimated 70% higher risk for serious infections than those exposed only in the first and/or second trimesters (aHR, 1.70; 95% CI, 0.96-3.01), but this association was not statistically significant.
• Exposure to high-placental-transfer TNF inhibitors was associated with a higher, though not statistically significant, risk for serious infections than exposure to low-placental-transfer TNF inhibitors at any time (aHR, 1.49; 95% CI, 0.83-2.69) or during the third trimester (aHR, 1.30; 95% CI, 0.65-2.61).

IN PRACTICE:

“Despite the potential relative increased risk of serious infections associated with third-trimester exposure and/or high placental transfer, the absolute risk was small, with up to 35 cases per 1000 person-years. This small absolute risk should be emphasized in counselling patients who often fear that their medications will harm their fetus,” the authors wrote.

“Controlling disease activity with [TNF inhibitors] may enable some women to carry their pregnancies to term, making a potentially increased risk of neonatal infections an acceptable trade-off in cases where these women might not have otherwise been able to have children,” they added.

SOURCE:

This study was led by Leah K. Flatman, PhD, Department of Epidemiology, Biostatistics and Occupational Health, McGill University in Montreal, Quebec, Canada. It was published online on December 1, 2025, in Arthritis & Rheumatology.

LIMITATIONS:

This study’s retrospective nature and use of administrative data may have led to potential residual confounding due to unmeasured factors such as BMI, smoking, and disease activity. The database captured only a commercially insured US population, potentially limiting generalizability to uninsured or publicly insured Americans. Additionally, the outcome definition relied on inpatient codes to identify serious infections, potentially missing infections recorded only in outpatient data.

DISCLOSURES:

The research received funding from the Canadian Institutes of Health Research project grant and an Arthritis Society Stars Career Development Award. None of the authors had relevant financial relationships to disclose.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.