Arthur R. Euler

Lower proportion of CD45R0+ cells and deficient interleukin-10 production by formula-fed infants, compared with human-fed, is corrected with supplementation of long-chain polyunsaturated fatty acids.

Background The immune consequences of adding 20:4n-6 and 22:6n-3 fatty acids to preterm infant formula are not known. Methods The effect of feeding preterm infants (14–42 days of age) human milk (Human Milk group), infant formula (Formula group), or formula with added long-chain polyunsaturated fatty acids 20:4n-6 and 22:6n-3 (Formula + LCP group) on isolated peripheral blood lymphocytes (by flow cytometry) and lipid composition (by gas–liquid chromatography) was determined. Lymphocytes were stimulated in vitro with phytohemagglutinin to measure soluble interleukin (sIL)-2R and IL-10 production (by enzyme-linked immunosorbent assay). Results With age, the percentage of CD3+CD4+ T cells and the percentage of CD20+ cells increased in the Human Milk and Formula + LCP groups (P < 0.05), but not in the unsupplemented Formula group. Compared with the Formula group, CD4+ cells from the Formula + LCP and Human Milk groups expressed more CD45R0 (antigen mature) and less CD45RA (antigen naive) at 42 days of age (P < 0.05). At 42 days, IL-10 production was lower (P < 0.05) in cells of the Formula group than in cells of the Human Milk group. Production of IL-10 by the cells of the Formula + LCP group was not different from that produced by the Human Milk group cells. An age-related decrease (P < 0.05) in sIL-2R production by Formula + LCP lymphocytes was observed, but sIL-2R production at 42 days in the Formula + LCP group did not differ significantly from that in the Human Milk group. Compared with Formula alone, adding LCP to formula resulted in a lower C18:2n-6 and higher C20:4n-6 content in lymphocyte phospholipids (P < 0.05). Conclusions Adding LCP to a preterm infant formula resulted in lymphocyte populations, phospholipid composition, cytokine production, and antigen maturity that are more consistent with that in human milk–fed infants. This may affect the ability of the infant to respond to immune challenges.

Evaluation of a long-chain polyunsaturated fatty acid supplemented formula on growth, tolerance, and plasma lipids in preterm infants up to 48 weeks postconceptional age

BACKGROUND The last trimester of pregnancy is a period of rapid accretion of long-chain polyunsaturated fatty acids, both in the central nervous system and the body as a whole. Human milk contains these fatty acids, whereas some preterm infant formulas do not. Infants fed formulas without these fatty acids have lower plasma and erythrocyte concentrations than infants fed human milk. Preclinical and clinical studies have demonstrated that single-cell sources (algal and fungal) of long-chain polyunsaturated fatty acids are bioavailable. A balanced addition of fatty acids from these oils to preterm formula results in blood fatty acid concentrations in low birth weight infants comparable to those of infants fed human milk. METHODS In the present study the growth, acceptance (overall incidence of discontinuation, reasons for discontinuation, overall incidence and type of individual adverse events), and plasma fatty acid concentrations were compared in three groups of infants fed a long-chain polyunsaturated fatty acid-supplemented preterm infant formula, an unsupplemented control formula, or human milk. The study was prospective, double-blind (formula groups only), and randomized (formula groups only). Two hundred eighty-eight infants were enrolled (supplemented formula group, n = 77; control formula group, n = 78; human milk group, n = 133). RESULTS Anthropometric measurements at enrollment, at first day of full oral feeding, and at both 40 and 48 weeks postconceptional age did not differ between the formula groups, whereas the human milk-fed group initially grew at a lower rate. The incidence of severe adverse events was rare and not significantly different between formula groups. The groups fed either human milk or supplemented formula had long-chain polyunsaturated fatty acid concentrations higher than those in the control formula group. CONCLUSIONS The results of this study demonstrate the safety and efficacy of a preterm formula supplemented with long-chain polyunsaturated fatty acids from single-cell oils.

Growth in human milk-Fed very low birth weight infants receiving a new human milk fortifier.

Background/Aims: Human milk fortification has been advocated to enhance premature infants’ growth. We, therefore, undertook this study of a new human milk fortifier containing more protein than a reference one. Methods: Open, randomized, controlled, multiclinic trial, with weekly growth parameters and safety evaluations in premature infants <1,500 g. Results: The 2 groups did not differ in demographic and baseline characteristics. The adjusted daily milk intake was significantly higher in the infants fed reference human milk fortifier (n = 29; 154.2 ± 2.1 vs. 144.4 ± 2.5 ml/kg/day, mean ± SE; p < 0.05). Both human milk fortifiers produced increases over baseline in weight, length, and head circumference, with greater gains observed in the new human milk fortifier-fed infants for the former two parameters (weight gain 26.8 ± 1.3 and 20.4 ± 1.2 g/day, p < 0.05; head circumference 1.0 ± 0.1 and 0.8 ± 0.1 cm/week; length 0.9 ± 0.1 and 0.8 ± 0.1 cm/week, respectively). Serum chemistries were normal and acceptable for age. Study events were typical for premature infants and similar in both groups. Conclusions: This new human milk fortifier had comparable safety to the reference human milk fortifier and promoted faster weight gain and head circumference growth.

Randomized Multicenter Trial Documenting the Efficacy and Safety of a Lactose-Free and a Lactose-Containing Formula for Term Infants

OBJECTIVE To evaluate the efficacy and safety of a new lactose-free infant formula. DESIGN Randomized, prospective, double-blind, controlled, outpatient, multicenter, parallel 12-week trial. SETTING Ambulatory-care facilities of the participating centers. SUBJECTS 137 healthy term infants (approximately 7 days old at the time of study enrollment). INTERVENTION Healthy term infants, whose mothers had decided not to breast-feed, were randomly assigned 1 of the 2 study formulas. MAIN OUTCOME MEASURES Weight, length, and occipitofrontal circumference measurements were obtained at baseline and when the infant was 2, 4, 8, and 12 weeks old. Formula acceptance and tolerance were also assessed at weeks 2, 4, 8, and 12. Serum albumin concentration, creatirune level, and blood urea nitrogen were determined at baseline and week 12. Adverse events were assessed throughout the study. STATISTICAL ANALYSES PERFORMED Each baseline anthropometric and laboratory variable was analyzed for comparability between groups using the Student t test and was also analyzed using a repeated-measures analysis of variance method. Covariance analysis was applied to the final laboratory data using the respective baseline data as covariates. Decisions about equality of mean responses to formula effects were based on the .05 level of significance in all cases. RESULTS One hundred four infants completed the study. No significant differences between the 2 formula groups were noted for any of the growth and blood parameters. APPLICATIONS This new formula is an effective and safe lactose-free nutrition alternative for infants who require such a diet.

Morphological and functional effects of 16,16-dimethyl-prostaglandin-E2 on mucosal adaptation after massive distal small bowel resection in the rat.

The ability of 16,16-dimethyl-prostaglandin-E2 (PGE) to augment mucosal adaptation 14 days after a 70% distal small bowel resection in the rat was evaluated. In resected (R) and sham operated (S) animals, subcutaneous PGE 75 mg/kg, 2 X/day, induced significant (p less than 0.05) increases in mucosal protein, DNA, and disaccharidase concentrations per centimetre of bowel. The respective per cent increases in the residual proximal small intestine compared with their respective untreated controls were: protein, R = 60%, S = 66%; DNA, R = 69%, S = 29%; maltase, R = 57%, S = 5%. The uptake of leucine by intestinal rings was significantly higher (50%) in the PGE treated group at a concentration of 2 mmol/l of substrate, while the uptake of glucose was similar in all groups. The drug appears to be an effective agent in stimulating morphological and functional adaptation after massive distal small bowel resection.

Augmentation of Mucosal Adaptation following Massive Small-Bowel Resection by 16,16-Dimethyl-Prostaglandin E2 in the Rat

Survival following massive resection of the small intestine is often possible due to substantial hyperplasia of the mucosal surface in the remaining small intestine. While nutrients provide the major stimulus for hyperplasia in the clinical setting, the availability of drugs to augment this process would have obvious therapeutic implications. We evaluated the ability of 16,16-dimethyl-prostaglandin E2 (PGE2 to augment mucosal hyperplasia following massive small bowel resection in the rat. Three groups of 7 Sprague-Dawley rats, 160 g body weight, were subjected to 70% jejunoileal resection. One group was given 150 micrograms/kg of 16,16-dimethyl-PGE2 intragastrically twice daily, a second group 75 micrograms/kg subcutaneously, and a third group was untreated. After 17 days, segmental evaluation of mucosal mass in the remaining small intestine was determined by measuring mucosal protein, DNA, and disaccharidase levels. A significantly greater increase in mucosal mass was developed in the duodenum proximal to the anastomosis in both treatment groups, but neither the proximal nor distal ileum demonstrated significantly more adaptation. Histological examination in the duodenum confirmed the presence of a greater adaptive response in both the intragastrically and subcutaneously treated animals. 16,16-dimethyl-PGE2 appears to augment mucosal adaptation following massive small bowel resection in the rat, primarily in the very proximal small intestine.

A New Arachidonic Acid (ARA) and Docosahexanoic Acid (DHA) Supplemented Preterm Formula: Growth and Safety Assessment. † 1440

A New Arachidonic Acid (ARA) and Docosahexanoic Acid (DHA) Supplemented Preterm Formula: Growth and Safety Assessment. † 1440

A New Arachidonic Acid (ARA) and Docosahexanoic Acid (DHA) Supplemented Preterm Formula: Effect on Plasma and Erythrocyte Phospholipid Fatty Acids † 1376

Objective: To evaluate phospholipid response of a preterm infant formula supplemented with Arachidonic Acid (ARA) and Docosahexanoic Acid (DHA) from microbial fermentation oils.

Comparison of Two Iron Fortification Levels (8 & 12 mg Fe) in Cows Milk-Based Formula: Effect on Growth and Hematology, Second Six Months of Life. |[dagger]| 567

Objective: To evaluate iron status in healthy iron sufficient infants fed an infant formula containing one of two iron fortification levels from six to twelve months of age.