Blood sampling for research purposes in children: a practical guide to volume limits and minimisation strategies

Blood sampling performed only for research purposes usually offers no direct benefit to the child, and children's limited total blood volume and susceptibility to anaemia call for a cautious, standardised approach. This review summarises published recommendations on blood sampling volumes for research purposes in children and translates them into practical guidance for protocol design and everyday research practice. Guidance from WHO, the European Commission, PedCRIN and ICH documents was synthesised together with current empirical literature on the safety of blood sampling and on volume-minimisation techniques in paediatric studies. Published recommendations are heterogeneous and rest on limited evidence. European recommendations propose that research-related blood loss should as a general rule not exceed 1% of total blood volume (TBV) at any single time point and 3% of TBV over 4 weeks. We present these as reference values in a weight-based table, applied over a rolling 4-week window. In children with clinically significant anaemia, research-only sampling should be deferred or individually justified. Residual diagnostic samples, small-volume collection tubes, sparse sampling with population pharmacokinetic modelling, and volumetric microsampling (VAMS/DBS) substantially reduce blood burden, although microsampling has analytical limitations. Practical tracking of cumulative blood volume and coordination between teams are described. Parental informed consent must be complemented by the child's assent, sought according to age and maturity and checked during the study. CONCLUSION: These reference values and minimisation strategies offer a practical starting point for protocol design and ethics review. They are not proof of safety and need individual adjustment in sick children. WHAT IS KNOWN: • Published recommendations on research blood sampling in children are heterogeneous; European recommendations propose ≤ 1% of total blood volume at a single time point and ≤ 3% over 4 weeks. • Evidence supporting these thresholds is limited. WHAT IS NEW: • This review translates these recommendations into a practical framework: a weight-based reference table, rolling 4-week tracking of research blood loss alongside clinical sampling, and coordination between clinical and research teams. • It summarises residual-sample and microsampling strategies, including their limitations.