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

Kelley L Baumgartel,Diane L Spatz,Dianxu Ren,Maureen W Groer,Yvette P Conley,Susan M Cohen

doi:10.1177/0890334416646725

Abstract

BackgroundBreast 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.ObjectiveThe 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.MethodsMilk 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.ResultsTrajectory 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.ConclusionMaternal IL SNPs may affect IL breast milk levels and IL milk levels may be associated with infant outcomes.

Highlights

Breast milk concentrations of immune components are variable between women and interleukin (IL) differences may be associated with infant outcomes
Maternal IL single nucleotide polymorphisms (SNPs) may affect IL breast milk levels and IL milk levels may be associated with infant outcomes
Serum interleukin (IL) levels are influenced by single nucleotide polymorphisms (SNPs)

Summary

Introduction

Breast milk concentrations of immune components are variable between women and interleukin (IL) differences may be associated with infant outcomes. Preterm infants no longer receive maternal immunological protection in utero; it is essential that they receive passive immunity through breast milk. Interleukins (ILs) are an integral part of the inflammatory response, and preterm infants are vulnerable to complications due, in part, to an underdeveloped immunological system. Interleukins are present in breast milk, their concentration is highly variable between women.[9] Breast milk from mothers with allergies is higher in IL4 concentration when compared to milk from mothers without allergies.[10,11] IL4 is relevant to the preterm population because serum IL4 induces both antibody and IgE production,[12] it is unclear if exogenous milk IL4 has this effect on the breastfed infant. Serum IL4 levels have been associated with 2 single nucleotide polymorphisms (SNPs) at the gene's promoter region,[14,15] this relationship has never been explored in breast milk

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Conclusion