Leukocytes in human breastmilk: mapping the evidence through a scoping review

Abstract

The immunological composition of breastmilk has gained research interest as breastfeeding correlates with improved health outcomes in infants, short and long term. Within this field, breastmilk leukocytes (BreLeuk) have remained underexplored. In this scoping review, we map and synthesize all available published literature on human BreLeuk to establish a State-of-the-Art. A systematic search across 4 databases from inception until February 10th 2025, yielded 216 relevant peer-reviewed research articles from 4336 collected abstracts. Colostrum was the most studied milk type. Macrophages were the most reported BreLeuk population with 110 associated studies (>50% of total), followed by T cells. On the other end, eosinophils and basophils were rarely studied (15 and 4 studies, respectively) and mast cells were investigated, but not found in human milk. Research has predominantly focused on analyzing BreLeuk relative proportions, immunophenotype, morphology, and phagocytosis/killing activity, and comparing to paired blood circulating leukocytes. Overall, BreLeuk research has been dominated by high-income countries (80%), with minimal representation from low-income regions (1.7%). Maternal demographics have been historically underreported, hampering correlations with BreLeuk composition, although the most recent studies have more consistently reported these variables. Over 63.9% of studies evaluated BreLeuk characteristics in healthy mothers, while the others studied conditions such as HIV (14 studies, 6.5%), and to a lesser extent allergies, obesity or infections. We provide a comprehensive database of human BreLeuk identification and reported phenotypes and functions, to facilitate future research.