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Serious Infections in Offspring Exposed to Tumor Necrosis Factor Inhibitors During Pregnancy: Comparison of Timing
Leah K Flatman1,2, Sasha Bernatsky1,2,3,4,5, Yvan St-Pierre2
1Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada.
Insights
Tumor necrosis factor inhibitors (TNFi) use in pregnancy did not significantly increase serious infection risk in newborns overall. However, third-trimester exposure showed a potential increased risk, warranting further investigation.
Area of Science:
- Immunology
- Pharmacology
- Pediatrics
Background:
- Tumor necrosis factor inhibitors (TNFi) are used to treat chronic inflammatory diseases.
- Understanding the risk of serious infections in offspring exposed to TNFi in utero is crucial for patient counseling and clinical practice.
Purpose of the Study:
- To evaluate the risk of serious infections in infants born to mothers who used TNFi during pregnancy.
- To analyze this risk based on the timing of TNFi exposure during pregnancy and the drug's placental transfer ability.
Main Methods:
- A retrospective cohort study using MarketScan data (2011-2021) identified pregnancies with chronic inflammatory diseases.
- TNFi exposure was defined by prescription fills, categorized by trimester and placental transfer.
- Cox proportional hazards models were used to assess the association between TNFi exposure and serious infections in the first year of life, adjusting for confounders.
Main Results:
- Of 56,866 offspring, 6.5% were exposed to TNFi. Overall TNFi exposure was not significantly associated with increased serious infection risk (HR 0.85).
- Offspring exposed during the third trimester showed a 70% higher risk of serious infections (HR 1.70), though not statistically significant.
- Exposure to TNFi with higher placental transfer ability showed a trend towards increased risk, particularly in the third trimester, but lacked statistical significance.
Conclusions:
- Overall TNFi exposure in utero is not linked to a statistically significant increase in serious infections in offspring.
- Exploratory findings suggest potential increased risk with third-trimester exposure and high-placental transfer TNFi, but these signals require further research due to imprecision.
Objective:
We evaluated serious infection risk in offspring exposed to tumor 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 at least one 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 vs 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 0.96-3.01). Additionally, we observed an increased risk with exposure to any TNFi with high 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.
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