Kathrine Agergård Kaspersen, István Barkos, Lotte Hindhede, Susan Mikkelsen, Khoa Manh Dinh, Nanna Brøns, Jacob Træholt, Christina Mikkelsen, Jakob Thaning Bay, Ole Birger Vesterager Pedersen, Sisse Rye Ostrowski, Erik Sørensen, Bitten Aagaard, Mie Topholm Bruun, Henrik Hjalgrim, Klaus Rostgaard, Henrik Ullum, Erzsébet Horváth‐Puhó, Christian Erikstrup
BACKGROUND AND OBJECTIVES: The demand for plasma-derived medicinal products underscores the need to assess health effects of plasma donation. This study examines the association between plasma donation rates and infection risk in a country with voluntary, non-remunerated donation. MATERIALS AND METHODS: From 2016 to 2024, 45,615 first-time plasma donors were enrolled in a cohort study with time-varying exposure. Follow-up began 90 days after the first plasma donation, with donation rates recalculated every 90 days. Donation rates were categorized as 0, 1 (reference), 2-3, 4-5 or 6-8 donations. Infection was defined using Danish health registers. Survival models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: The median plasma donation rate was 2 (Q1, 1; Q3, 4). During follow-up, 15,498 donors experienced an infection. A trend of decreasing HRs for infection was observed with higher donation rates compared with a single donation (0 donations: HR: 0.89, 95% CI: 0.86-0.93; 2-3 donations: HR: 0.85, 95% CI: 0.81-0.89; 4-5 donations: HR: 0.65, 95% CI: 0.59-0.72; and 6-8 donations: HR: 0.48, 95% CI: 0.36-0.62). Findings were consistent across multiple regression models. CONCLUSION: In this study, higher plasma donation rates were associated with lower infection risk. Importantly, this inverse association is likely due to bias inherent to observational designs, particularly the internal healthy donor effect, which limits interpretation. Thus, no causal relationship between plasma donation rates and infection risk can be inferred. This underscores the challenges of assessing plasma donation safety using non-randomized data.