Effect of Promoter Polymorphisms on Cytokine Concentration in Preterm Breast Milk and Subsequent Infant Outcomes

Abstract

Background: Breast milk concentrations of immune components are variable between women and interleukin (IL) differences may be associated with infant outcomes. Molecular mechanisms for milk variability remain unknown. Objective: The aims were to (1) examine the relationship between maternal IL genotypes and milk concentrations of IL4, IL6, and IL10, (2) describe the trajectories of milk IL change, (3) examine whether maternal IL genotypes predict IL trajectories and/or average weekly IL concentration, and (4) examine if weekly IL levels and/or IL trajectories are associated with infant outcomes. Methods: Milk aliquots were collected from each feeding of mother’s own milk and pooled weekly. DNA was extracted from 1 sample of each mother’s breast milk whey (n = 64), and single nucleotide polymorphisms (SNPs) of IL genes were genotyped. Milk IL concentrations were measured and trajectory analysis examined IL milk change over time. Multivariate breast milk IL concentration analyses controlled for gestational age and prepregnancy body mass index. Multivariate infant outcome (n = 73) analyses controlled for gestational age and the ratio of human milk to total milk. Results: Trajectory analysis resulted in linear group shapes, with 2 distinct subgroups in IL6 and 3 subgroups in IL4 and IL10. Trajectory groups trended toward significance with calprotectin, intraventricular hemorrhage, and blood transfusions. Multivariate analyses resulted in trending associations between maternal SNPs and subsequent IL6 and IL10 milk levels. There was a trending relationship between IL milk levels and both fecal calprotectin and intraventricular hemorrhage. Conclusion: Maternal IL SNPs may affect IL breast milk levels and IL milk levels may be associated with infant outcomes.