Osmolality of fortified donor human milk: An experimental study.

BACKGROUND: We quantify the osmolality of human milk fortified with human milk fortifiers (HMFs), powder infant formulas and protein additives. METHODS: Commercial liquid HMFs and powder infant formulas were added to pasteurized pooled donor human milk in triplicate and stirred. The osmolality of unfortified and fortified human milk at 22, 24, 26, 27, 28, and 30 kcal/oz (0.73, 0.8, 0.87, 0.9, 0.93, and 1 kcal/ml, respectively) was determined using freezing-point depression. RESULTS: The osmolality of fortified human milk associated with energy density in a linear relationship regardless of the fortification strategies. Multiple liquid HMFs and every powder infant formula exceeded the osmolality threshold of 450 mOsm/kg H2 O within the energy densities tested. CONCLUSION: The osmolality of fortified human milk is highly variable and should be considered when selecting a fortifying agent for human milk.

Displacement of human milk during fortification: An experimental study.

BACKGROUND: This study quantified the displacement of human milk by commercial human milk fortifiers (HMFs) and infant formulas. METHODS: Commercial liquid HMFs and powder infant formulas were added to pasteurized pooled donor human milk in triplicate, stirred, and weighed. The difference in weight between unfortified and fortified human milk at 22, 24, 26, 27, 28, and 30 kcal/ounce was calculated. RESULTS: The displacement of human milk by liquid HMFs and powder infant formulas and powder HMF was highly associated with energy density. A human milk-derived HMF displaced significantly more human milk when compared with bovine milk-derived HMFs at equivalent energy densities. Similarly, powder infant formulas displaced less human milk when compared with a powder HMF, and the addition of hydrolyzed powder infant formulas resulted in less human milk displacement when compared with nonhydrolyzed powder infant formulas. CONCLUSIONS: The displacement of human milk by commercial liquid HMFs and infant formulas must be considered when selecting a fortifying strategy.

Nutrient Composition of Donor Human Milk and Comparisons to Preterm Human Milk.

BACKGROUND: Human milk is the preferred diet for very low birth weight (VLBW, <1500 g) infants. When mother's own milk is unable to meet the needs of VLBW infants, donor human milk (DHM) is the preferred alternative. Unfortunately, the composition of DHM remains elusive and no comparative studies between preterm human milk and DHM have been performed previously. OBJECTIVES: We aimed to analyze the nutrient content of commercial pooled DHM and compare nutrient content in DHM with that of early and mature preterm human milk. METHODS: We analyzed nutrient content in 15 DHM samples provided from 7 commercial milk banks including calories, carbohydrate, fat, protein, sodium, chloride, potassium, zinc, calcium, phosphorus, magnesium, and vitamin D and compared each nutrient to early (7 d of life) and mature (28 d of life) preterm human milk samples (n = 28-36 per nutrient, gestational age = 28 ± 3 wk). Protein-to-energy ratio and carbohydrate-to-nonprotein energy ratio were calculated for each sample and compared. RESULTS: Mean values for all macro- and micronutrients in DHM are reported. In comparison to early or mature preterm human milk, DHM had significantly lower protein, sodium, chloride, potassium, and zinc content. Calorie, carbohydrate, calcium, phosphorus, magnesium, and vitamin D content did not differ statistically between DHM and early or mature preterm human milk. Fat content was modestly lower in early but not mature human milk when compared with DHM. CONCLUSIONS: We provide mean values for several macro- and micronutrients for DHM and identify key differences between DHM and preterm human milk, which may be considered when designing human milk-based feeding plans. This study was registered at clinicaltrials.gov as NCT05742815.

Acid/base balance in fortified donor human milk: An experimental study.

BACKGROUND: Our goal was to quantify the pH and total acidity of human milk fortified with human milk fortifiers (HMFs), powder infant formulas, and protein additives. METHODS: Commercial liquid HMFs and powder infant formulas were added to pasteurized pooled donor human milk in triplicate and stirred. The pH of unfortified and fortified human milk at 22, 24, 26, 27, 28, and 30 kcal/ounce (624, 680, 737, 765, 794, and 850 kcal/g, respectively) was determined using a pH meter. Phenolphthalein acidity at 24 and 30 kcal/ounce (680 and 850 kcal/g, respectively) was determined using diluted sodium hydroxide. RESULTS: The pH of unfortified human milk increased within the first hour (6.52 ± 0.06 vs 6.62 ± 0.05, P < 0.0001). Changes in pH largely correlated with caloric density; however, directional changes varied considerably between HMFs and powder infant formulas. Two liquid HMFs demonstrated modest reductions in pH with increasing caloric density whereas one liquid HMF alkalinized human milk with increasing caloric density (analysis of variance P < 0.0001). Phenolphthalein acidity was significantly higher for five HMFs and lower for one HMF at 30 kcal/ounce (850 kcal/g) but not 24 kcal/ounce (680 kcal/g). Powder infant formulas generally increased pH with increasing caloric density (analysis of variance P < 0.0001), but no differences in phenolphthalein acidity were noted. CONCLUSION: Changes in acid/base balancefor fortified human milk are variable and may be a consideration when selecting a fortifying agent for human milk.

Nutrient composition of preterm mother's milk and factors that influence nutrient content.

BACKGROUND: Breast milk feedings are the optimal feeding choice for premature infants. Clinicians depend on accurate nutrient profiles of the breast milk in order to make informed decisions regarding the need for nutrient supplementation. Existing data for nutrient composition of preterm breast milk are dated and not representative of the current population of women delivering prematurely in the United States. OBJECTIVES: The purpose of this prospective, longitudinal, single-center observational study was to measure the macronutrient and micronutrient composition of breast milk expressed by mothers, including women who self-identify as black, delivering preterm infants at ≤33 completed weeks of gestation. METHODS: We collected breast milk samples from mothers of preterm infants admitted to the neonatal intensive care unit at Augusta University Medical Center from January 2019 through November 2019. Mother's milk samples were collected on postpartum days 7, 14, 21, and 28 and analyzed for macronutrients (energy, fat, protein, and carbohydrates) and micronutrients (sodium, potassium, chloride, calcium, phosphorus, magnesium, vitamin D, and zinc). RESULTS: Thirty-eight mothers, mean age 27 ± 5.1 y and majority black (66%), provided milk for the study. The mean estimated gestational age and birth weight were 28.2 ± 2.8 weeks of gestation and 1098 ± 347 g, respectively, with 42% of mothers in the cohort delivering before week 28 of pregnancy. Differences in protein, sodium, potassium, calcium, phosphorus, and zinc concentrations based on race, day, and milk volume were identified. Dilution effects for protein, sodium, chloride, and vitamin D concentrations over time were identified. CONCLUSIONS: Our study is among the first to characterize breast milk composition from women who delivered extremely preterm infants and adds to the evidence that race, gestational age, and volume influence the composition of preterm mother's milk. These factors should be considered when designing mother's milk-based feeds for premature infants.

Review of Preterm Human-Milk Nutrient Composition.

BACKGROUND: The human milk-fed preterm infant is at risk for growth failure, micronutrient deficiencies, and neurocognitive delay. Although protective and better tolerated than formula, human milk alone cannot meet the high nutrient requirements of this population, and fortification is necessary. Clinicians use assumptions of preterm human-milk composition to determine the type and quantity of fortification. OBJECTIVES: The objectives of this review were to identify evidence of macronutrient and micronutrient concentration in preterm human milk and to identify knowledge gaps regarding composition. METHODS: PubMed and the Cumulative Index to Nursing and Allied Health Literature were used to identify original articles published between January 1950 and December 2019. RESULTS: Twenty-seven articles were found containing original data on macronutrients and micronutrients. Most (67%) of the studies published after 2011 measured the macronutrients and included gestational ages from 28 to 36 weeks. Milk collection methods, experimental design, and analytical methods varied between studies. There are 15 countries represented in this review; all of the American studies (n = 7) were published from 1980 to 1984. CONCLUSIONS: African American women, or women delivering before 28 weeks' gestation are not represented in the literature. Accurate and targeted human-milk fortification depends on comprehensive, complete, and representative human-milk nutrient data. We have aggregated all available preterm human-milk macronutrient and micronutrient data and reported trends associated with lactation stage and gestational age. This report can aid in the design of feeding plans that are appropriate for the gestational age of the preterm infant and the lactation stage of the breastmilk.

Niacin protects against abdominal aortic aneurysm formation via GPR109A independent mechanisms: role of NAD+/nicotinamide.

AIMS: Chronic adventitial and medial infiltration of immune cells play an important role in the pathogenesis of abdominal aortic aneurysms (AAAs). Nicotinic acid (niacin) was shown to inhibit atherosclerosis by activating the anti-inflammatory G protein-coupled receptor GPR109A [also known as hydroxycarboxylic acid receptor 2 (HCA2)] expressed on immune cells, blunting immune activation and adventitial inflammatory cell infiltration. Here, we investigated the role of niacin and GPR109A in regulating AAA formation. METHODS AND RESULTS: Mice were supplemented with niacin or nicotinamide, and AAA was induced by angiotensin II (AngII) infusion or calcium chloride (CaCl2) application. Niacin markedly reduced AAA formation in both AngII and CaCl2 models, diminishing adventitial immune cell infiltration, concomitant inflammatory responses, and matrix degradation. Unexpectedly, GPR109A gene deletion did not abrogate the protective effects of niacin against AAA formation, suggesting GPR109A-independent mechanisms. Interestingly, nicotinamide, which does not activate GPR109A, also inhibited AAA formation and phenocopied the effects of niacin. Mechanistically, both niacin and nicotinamide supplementation increased nicotinamide adenine dinucleotide (NAD+) levels and NAD+-dependent Sirt1 activity, which were reduced in AAA tissues. Furthermore, pharmacological inhibition of Sirt1 abrogated the protective effect of nicotinamide against AAA formation. CONCLUSION: Niacin protects against AAA formation independent of GPR109A, most likely by serving as an NAD+ precursor. Supplementation of NAD+ using nicotinamide-related biomolecules may represent an effective and well-tolerated approach to preventing or treating AAA.

Role of myeloperoxidase in abdominal aortic aneurysm formation: mitigation by taurine.

Oxidative stress plays a fundamental role in abdominal aortic aneurysm (AAA) formation. Activated polymorphonuclear leukocytes (or neutrophils) are associated with AAA and express myeloperoxidase (MPO), which promotes inflammation, matrix degradation, and other pathological features of AAA, including enhanced oxidative stress through generation of reactive oxygen species. Both plasma and aortic MPO levels are elevated in patients with AAA, but the role of MPO in AAA pathogenesis has, heretofore, never been investigated. Here, we show that MPO gene deletion attenuates AAA formation in two animal models: ANG II infusion in apolipoprotein E-deficient mice and elastase perfusion in C57BL/6 mice. Oral administration of taurine [1% or 4% (wt/vol) in drinking water], an amino acid known to react rapidly with MPO-generated oxidants like hypochlorous acid, also prevented AAA formation in the ANG II and elastase models as well as the CaCl2 application model of AAA formation while reducing aortic peroxidase activity and aortic protein-bound dityrosine levels, an oxidative cross link formed by MPO. Both MPO gene deletion and taurine supplementation blunted aortic macrophage accumulation, elastin fragmentation, and matrix metalloproteinase activation, key features of AAA pathogenesis. Moreover, MPO gene deletion and taurine administration significantly attenuated the induction of serum amyloid A, which promotes ANG II-induced AAAs. These data implicate MPO in AAA pathogenesis and suggest that studies exploring whether taurine can serve as a potential therapeutic for the prevention or treatment of AAA in patients merit consideration.NEW & NOTEWORTHY Neutrophils are abundant in abdominal aortic aneurysm (AAA), and myeloperoxidase (MPO), prominently expressed in neutrophils, is associated with AAA in humans. This study demonstrates that MPO gene deletion or supplementation with the natural product taurine, which can scavenge MPO-generated oxidants, can prevent AAA formation, suggesting an attractive potential therapeutic strategy for AAA.