Richard J. Schanler

Origin of intact lactoferrin and its DNA-binding fragments found in the urine of human milk-fed preterm infants. Evaluation by stable isotopic enrichment.

ABSTRACT: The origin of intact (78-kD) lactoferrin found in the urine of human milk-fed preterm infants was investigated using human milk containing proteins enriched with [13C]leucine and [15N2]lysine or [2H4]lysine. Mothers of infants selected for the study were infused i.v. with [13C]leucine and [15N2]lysine or [2H4]lysine to label milk proteins. The labeled milk was collected from each mother, pooled, fortified with a lyophilized human milk fraction, and fed to her preterm infant by continuous orogastric infusion for a period of 48 h. Urine was collected from each infant for 96 h. Intact lactoferrin (78 kD) and DNA-bioding lactoferrin fragments (51 and 39 kD) were purified from the urine by affinity chromatography on columns of immobilized single-stranded DNA-agarose. The concentration and isotopic enrichment of the intact lactoferrin and DNA-binding fragments were determined separately after their isolation by high-performance reverse-phase (phenyl) chromatgraphy. Mass spectral analyses indicated that the isotopic enrichment of the purified urinary lactoferrin was 87 to 100% of that in the labeled human milk lactoferrin. Similar results were obtained for the isolated DNA-binding lactoferrin fragments. The ratios of isotopically labeled leucine to lysine in the purified milk lactoferrins and urinary lactoferrins were similar for each mother/infant pair. Isotopically labeled lysine, added to the milk as free amino acid, was not incorporated into the purified urinary lactoferrin. These results demonstrate that undegraded (78-kD) lactoferrin of maternal origin is absorbed by the gut and excreted intact in the urine of preterm infants; nearly all of the urinary lactoferrin was of maternal origin. The possible immunoregulatory functions of the absorbed intact, maternal lactoferrin are discussed.

Concentrations of IL‐10 in preterm human milk and in milk from mothers of infants with necrotizing enterocolitis

Background: Despite the protective effects of human milk against necrotizing enterocolitis, the incidence is highest in the extremely premature infant, and only minimally decreased with feeding human milk. This suggests that certain protective agents may be lower in milk from mothers delivering extremely premature infants. The anti‐inflammatory cytokine IL‐10 was one possibility. Aim: We hypothesized that low concentrations of IL‐10 in preterm milk contribute to the development of necrotizing enterocolitis in extremely premature infants. Methods: IL‐10 in human milk collected at weeks 1, 2, and 4 postpartum was measured by ELISA in mothers of infants born extremely premature at 23–27 wk gestation (group EP), premature at 32–36 wk gestation (group P), and term at 38–42 wk gestation (group T). Single milk samples were collected from a separate group of mothers whose infants developed necrotizing enterocolitis. Results: There were no significant differences in concentrations of milk IL‐10 among groups EP, P, or T. Concentrations of IL‐10 declined as lactation progressed (p > 0.001). IL‐10 in milk was frequently undetected in all groups, but even more so in the milk of the group of women whose infants had necrotizing enterocolitis (86%) than in groups EP (40%) and P (27%) (p > 0.01).

Nutrient Accretion in Preterm Infants Fed Formula With Different Protein: Energy Ratios

BACKGROUND Although standard formulas for preterm infants promote intrauterine rates of weight gain, fat deposition in preterm infants fed these formulas has been reported to be considerably higher than that in the fetus. We hypothesized that a preterm infant formula with a higher protein:energy (P:E) ratio would promote accretion rates of fat, fat-free mass, and minerals closer to those of the fetus. METHODS As part of a larger study to determine whether accretion rates of fat and fat-free mass closer to those of the fetus can be achieved with a higher P:E ratio, we present a descriptive analysis of 72-h nutrient balance studies performed on a subset (n = 15/30) of the infants randomly assigned to be fed formula with a P:E ratio of either 3.2 g/100 kcal or 2.6 g/100 kcal. RESULTS Despite the higher intake and net absorption of nitrogen by infants fed the higher P:E formula, there was no statistically significant difference in net nitrogen retention between groups. There also were no statistically significant differences between groups in digestible energy, metabolizable energy, energy expenditure, or energy storage. Thus, partitioning of stored energy as protein and fat did not differ between groups. The retention of calcium, phosphorus, sodium, potassium, copper, and zinc also did not differ between groups, and nitrogen intake did not affect mineral retention. CONCLUSIONS In this study, formula for preterm infants with a P:E ratio of 3.2 g/100 kcal vs. 2.6 g/100 kcal provided no apparent benefit in terms of the proportion of fat to lean tissue accretion as determined from nutrient balance data.

Human milk supplementation for preterm infants: Human milk supplementation for preterm infants

Nutrition support of the premature infant must be designed to compensate for metabolic and gastrointestinal immaturity, immunologic compromise, and associated medical conditions. The beneficial effects of human milk extend to the feeding of premature infants. However, nutritional concerns arise because the quantity of nutrients in human milk may not meet the great nutrient needs of the premature infant born weighing less than 1500 g. Human milk fortifiers are available to provide optimum nutrition. This review summarizes the benefits and limitations of human milk for the premature infant.

Ehrlich-Koldovsky Young Investigator Award

The Society recognizes investigators at the junior faculty level who have begun to make outstanding, original scientific contributions to the study of human milk and lactation with the EHRLICH-KOLDOVSKY YOUNG INVESTIGATOR AWARD FOR RESEARCH IN HUMAN MILK AND LACTATION. Paul Ehrlich was known for his work on the principles of immunology and theories of antibody responses as magic bullets which would go straight to the organisms at which they were aimed. Otakar Koldovsky studied intestinal maturation during the suckling period and the importance of mammalian milk for its growth-promoting properties, exclusive of the known nutrients present. This led him to develop the concept of “Biologically Active Substances” in milk and to explore what these substances might be and how they might act using artificially reared animals, the ‘pup in the cup’ model. Ehrlich-Koldovsky Young Investigator awardees are listed below. Additional information about Dr. Koldovsky can be found on the Society website at www.ISRHML.org.

Macy-György Award

At each bi-annual international meeting since 1995, the Executive Committee of the International Society for Research in Human Milk and Lactation has honored outstanding investigators in the field of human milk and lactation. Senior scientists whose work has been recognized internationally and whose many papers have appeared in prominent peer-review journals are candidates for the MACY-GYORGY AWARD FOR RESEARCH IN HUMAN MILK AND LACTATION. This award honors individuals who have made outstanding, original scientific contributions to the study of human milk and lactation. This award is appropriately named for two outstanding scholars in the field of human milk and lactation, Drs. Icie G. Macy and Paul Gyorgy.