Evaluating the effect of random multi-donor pooling on the nutritional variability in donor human milk using computer modeling

Authors: SMITH, R. MITCHEL - University Of North Carolina; RICHTER, SCOTT - University Of North Carolina; IWAYEMI, ESTHER - University Of North Carolina; MANSEN, KIMBERLY - Path; ISRAEL-BALLARD, KIERSTEN - Path; HAMPEL, DANIELA - University Of California, Davis; Shahab-Ferdows, Setareh; Allen, Lindsay; BODE, LARS - University Of California, San Diego; PERRIN, MARYANNE - University Of North Carolina

Submitted to: Maternal and Child Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/4/2025
Publication Date: 1/8/2026
Citation: Smith, R., Richter, S., Iwayemi, E., Mansen, K., Israel-Ballard, K., Hampel, D., Shahab-Ferdows, S., Allen, L.H., Bode, L., Perrin, M.T. 2026. Evaluating the effect of random multi-donor pooling on the nutritional variability in donor human milk using computer modeling. Maternal and Child Nutrition. 22(1). Article e70158. https://doi.org/10.1111/mcn.70158.
DOI: https://doi.org/10.1111/mcn.70158

Interpretive Summary: The amounts of some nutrients in donor human milk (DHM) are subjected to a large variation driven by the number of unique donors included in the pool. Therefore, we investigated how that number of unique donors randomly chosen for a pool affect the human milk compositions of the pool by assessing macronutrients, vitamins, minerals, and bioactive factors in DHM. Further, we estimated the smallest number of donors needed to reach the target values for true protein, fat, and the human milk oligosaccharide DSLNT in 80% of the pools, consisting of 2 to 10 donors at random using statistical analyses. These models resulted in 1000 theoretical pools using data from 400 approved milk bank donors. The variation of human milk composition was quantified as a Nutrient Inequality Index (NII) which was computed as the ratio of the 90th percentile to the 10th percentile for each model. We found that a NII <1.3 for macronutrients when 5 or more donors were randomly pooled. For micronutrients, such as biotin, riboflavin, B6, B12, pantothenic acid, iron, copper, zinc, DSLNT and lactoferrin, the NII exceeded 2.0 and therefore none of the pooling models met the respective target values. Thus, only the macronutrient variability can be controlled using the radom pooling strategy, while this strategy is not successful for many micronutrients. Further research is needed to asses if current fortifiers are the needed link for meeting the target values for these micronutrients in DHM.

Technical Abstract: Background: Some nutrients vary 3-fold or more in donor human milk (DHM) and are influenced by the number of unique donors included in the pool. Aim: Primary: characterize how the number of unique donors randomly combined into a pool influences the variability of macronutrients, vitamins, minerals, and bioactive factors in DHM. Secondary: determine the minimum number of donors required so that 80% of pools meet pre-defined targets for true protein, fat, and the human milk oligosaccharide DSLNT. Methods: We used Monte Carlo simulations to evaluate the impact of randomly combining 2 to 10 donors per pool of DHM. Each simulation created 1000 theoretical pools using data from 400 approved milk bank donors to four US milk banks as the underlying dataset. Variability in nutrients was quantified as a Nutrient Inequality Index (NII) which was computed as the ratio of the 90th percentile to the 10th percentile for each simulation (2 to 10 donors). Results: An NII <1.3 could be obtained for macronutrients by randomly pooling 5 or more donors; however, the NII would still exceed 2.0 for many micronutrients including biotin, riboflavin, B6, B12, pantothenic acid, iron, copper, zinc, DSLNT and lactoferrin. We were unable to meet target nutrient values with any pooling simulations. Conclusion: Randomly pooling 5+ donors is a useful tool for milk banks to control macronutrient variability. Clinicians should expect an NII >2-fold for many micronutrients in DHM. Whether current fortifiers are effective at meeting preterm micronutrient goals with DHM is an important future area of research.