TNF-alpha Concentrations in Serum and Human Milk of Mothers With Insufficient Versus Sufficient Milk Production

Walker Rachel, Gernand Alison, Schozer Frederick, Tso Patrick, Wagner Erin, Riddle Sarah, Ward Laura, Thompson Amy, Nommsen-Rivers Laurie
2021 Current Developments in Nutrition  
Objectives Obesity and poor metabolic health are associated with poor lactation outcomes, potentially driven by elevated tumor necrosis factor alpha (TNF-α) from chronic inflammation. TNF-α reduces lipoprotein lipase (LpL) activity, limiting triglyceride (TG) uptake by the mammary gland for milk synthesis. Our objective here is to determine if TNF-α concentrations in serum and milk are higher in mothers with severely low compared to sufficient milk production and if TNF-α is associated with
more » ... ma TG. Methods Mothers screened for low milk production were categorized into very low (VL; 177 [87,219] mL/d; n = 23) and moderately low/normal (ML; Median [IQR]: 467 [373,655] mL/d; n = 20) milk production. An external control group had sufficient milk production (EC; 783 [717,818] mL/d; n = 18). Mothers provided a spot milk sample at a morning clinic visit, where fasting blood samples were taken for clinical metabolic health measures. TNF-α concentrations were measured in duplicate by high-sensitivity ELISA in serum and aqueous milk. Group differences were assessed by Wilcoxon Rank Sums Tests or Fisher's Exact Chi Square Test (α = 0.05). Correlations were assessed by Spearman rank order. Results Mothers were 31.3 [27.3, 34.1] years old, delivered at gestational age of 39.4 [38.6, 40.3] weeks, and were 43 [35, 56] days postpartum, with no significant differences among groups. Milk TNF-α was detected in 47% of samples (1.3 [0.8, 2.2] pg/mL). The proportion of detectable TNF-α (D-TNF) in milk was higher in VL compared with ML and EC (71%, 32%, 33% respectively; p = 0.02). Compared to undetected (U-TNF), subjects with D-TNF in milk had higher plasma TG (D-TNF: 94 [68,140] mg/dL; U-TNF: 60 [49, 84] mg/dL; p = 0.001). Serum TNF-α was not significantly different by group (VL: 6.3 [5.8, 7.0] pg/mL; ML: 6.1 [5.6, 6.5]; EC: 5.8 [5.3, 6.6]; p = 0.31), but was correlated with plasma TG (ρ = 0.40, p = 0.002). Conclusions In this exploratory cohort, TNF- α levels were higher in milk from mothers with low milk production, and both milk and serum TNF- α was associated with higher plasma TG. This suggests that proximal TNF-α expression is more associated with reduced mammary LpL activity than circulating serum TNF-α, leading to low milk production. Funding Sources NIH and USDA.
doi:10.1093/cdn/nzab046_123 fatcat:g3r6xgdebbejtmoz5hu2dgeop4