Blood sample volumes in child health research: review of safe limits.

OBJECTIVE: To determine paediatric blood sample volume limits that are consistent with physiological "minimal risk."
METHODS: A literature review was performed to search for evidence concerning the adverse effects of blood sampling in children and for guidelines on sampling volume in paediatric research. The search included Medline, EMBASE, other web-based and non-web-based sources and the bibliographies of the sources identified. Experts were also consulted.
FINDINGS: Five studies and nine guidelines were identified. Existing guidelines specify paediatric blood sample volume limits ranging from 1% to 5% of total blood volume (TBV) over 24 hours and up to 10% of TBV over 8 weeks. The evidence available is limited and includes findings from non-randomized studies showing a minimal risk with one-off sampling of up to 5% of TBV.
CONCLUSION: The evidence available is consistent with the conclusion that all identified guidelines are within the limits of "minimal risk." However, more and better evidence is required to draw firmer conclusions. Researchers and institutional review boards need to take into account the total sampling volume needed for both clinical care and research rather than for each alone. The child's general state of health should be considered and extra caution should be observed particularly with children whose illness can deplete blood volume or haemoglobin or hinder their replenishment. Local policies must also address the appropriateness and local acceptability of collection procedures and of the blood volumes drawn.