Fatty acid balance studies in preterm infants fed formula milk containing long-chain polyunsaturated fatty acids (LCP) II

A milk formula (Prematil-LCP) containing long-chain polyunsaturated fatty acids (LCP) and with a fatty acid profile closely resembling breast milk has recently been introduced for preterm infants. A double-blind randomized controlled trial was performed comparing fatty acid absorption from Prematil-LCP (n = 10) and standard Prematil (n = 10). Formula-fed preterm infants underwent 3 d fat balances (once full enteral feeds were established) along with a parallel human milk fed group (n = 11). Plasma samples were taken on the last day. Median total fat excretion (absorption, %) was 2.34 g kg (82.0), 2.64 g kg (82.9) and 1.65 g kg (87.8) with Prematil, Prematil-LCP and human milk feeding, respectively. This reflected differences in the excretion and absorption of long-chain saturated fatty acids. All groups excreted detectable LCP. LCP disappearance was higher in infants fed human milk than in those fed Prematil-LCP, particularly for n -6 LCP (p <0:01). Nevertheless, excreted LCP equated to <30% dietary intake, with Prematil-LCP feeding. Plasma lipid fatty acid composition reflected differences in dietary LCP intake.     

Polyunsaturated fatty acids in infant nutrition

The availability of long-chain polyunsaturated fatty acids (LCP), such as arachidonic (C20:4n-6) and docosahexaenoic (C22:6n-3) acids, is important for early human growth and development. The capacity for endogenous synthesis of LCP from the precursor fatty acids lineoleic (C18:2n-6) and alpha-linolenic (C18:3n-3) acid is limited in preterm and probably also in term infants. In utero, LCPs seem to be transferred preferentially from the mother to the foetus by the placenta. After birth, breastfed infants receive preformed dietary LCP with human milk. In contrast, most current infant formulae are devoid of LCP. Premature infants fed such formulae develop rapid LCP depletion of plasma and tissue lipids, which is associated with reduced visual acuity during the first postnatal months. Therefore, LCP enrichment of formulae for premature infants is desirable. Recent observations indicate that term infants fed conventional formulae also exhibit lower plasma LCP values and may show functional disadvantages, but these data require further confirmation prior to drawing definite conclusions.     

Plasma fatty acid composition during the first week of life following feeding with human milk or formula

Plasma fatty acids were studied in 20 full-term newborn infants fed human milk and in 17 newborn infants of identical characteristics fed an adapted cow's milk formula. Plasma fatty acids were measured in cord blood and at 7-9 days of age. No differences were present at birth but, after a period of feeding, infants receiving breast milk had higher plasma concentrations of stearic acid, di-homo-gamma-linolenic acid and arachidonic acid, while infants receiving formula had a higher plasma concentration of oleic acid. The importance of these findings in relation to the lipidic structure of the nervous system remains to be determined.     

Plasma Fatty Acid Composition during the First Week of Life Following Feeding with Human Milk or Formula

ABSTRACT. Plasma fatty acids were studied in 20 full-term newborn infants fed human milk and in 17 newborn infants of identical characteristics fed an adapted cow's milk formula. Plasma fatty acids were measured in cord blood and at 7–9 days of age. No differences were present at birth but, after a period of feeding, infants receiving breast milk had higher plasma concentrations of stearic acid, di-homo-γ-linolenic acid and arachidonic acid, while infants receiving formula had a higher plasma concentration of oleic acid. The importance of these findings in relation to the lipidic structure of the nervous system remains to be determined.     

Fatty acid composition of human milk during the 1st month after term and preterm delivery

The fatty acid composition of human breast milk was determined longitudinally after term and preterm delivery by high resolution gas liquid chromatography. Milk samples were obtained at days 5, 10, 20 and 30 after term (n = 38) or preterm (n = 19) delivery. The saturated fatty acids C10:0 and C12:0 and the polyunsaturates linoleic acid (C18:2ω-6) and α-linolenic acid (C18:3ω-3) increased significantly from day 5 to day 10, whereas arachidonic acid (C20:4ω-6), total ω-6 long-chain polyunsaturates (LCP), docosahexaenoic acid (C22:6ω3) and total ω-3 LCP decreased significantly. Term and preterm milk did not differ in percentage content of linoleic acid, α-linolenic acid and LCP at any time point. Preterm milk contained significantly more medium and intermediate chain fatty acids (C10:0, C12:0 and C14:0) than term milk on days 5 (12.28 vs 9.78%; P > 0.05), 10 (16.25 vs 12.62%; P > 0.05) and 20 (17.29 vs 13.47%; P > 0.005). Conclusion The milk of mothers of preterm infants is not better suited to meet the high LCP requirements of their infants during the first weeks after birth. The slightly higher proportion of medium and intermediate chain fatty acids in preterm milk during the 1st month after birth might be advantageous for the fat and calcium absorption of preterm infants. Received: 22 February 1996 / Accepted: 1 August 1996     

Docosahexaenoic and arachidonic acid content of serum and red blood cell membrane phospholipids of preterm infants fed breast milk,standard formula or formula supplemented with n-3 and n-6 long-chain polyunsaturated fatty acids

The contents of docosahexaenoic (DHA) and arachidonic acid (AA) of plasma and red blood cell membrane phospholipids were studied in 41 very low birth weight infants fed either breast milk (n=18), a standard formula without long-chain polyunsaturated fatty acids with 20 or 22 carbon atoms (LCP) but with -linolenic acid and linoleic acid (n=11) or a formula additionally supplemented with n-3 and n-6 LCP in relations typical for human milk (n=12) after 2, 6, and 10 weeks of feeding. The content of DHA and AA in plasma phospholipids declined in the infants fed the LCP-free formula but remained more or less constant during the whole feeding period in those infants fed breast milk as well as in those fed the LCP-supplemented formula. The differences between the group fed the LCP-free standard formula and the two groups fed LCP-containing diets became significant during the first 2 weeks of feeding. In contrast, there were no differences between the group fed breast milk and the group fed the supplemented formula during the study period. Similar effects could be observed regarding the composition of red blood cell membrane phospholipids, but the differences between the infants fed the LCP-free standard formula and the two other groups with LCP-containing diets were significant only for AA. The data indicate that very low birth weight infants are unable to synthesize LCP from -linolenic acid and linoleic acid in sufficient amounts to prevent a decline of LCP in plasma and red blood cell phospholipids. Additionally, the data show, that supplementation of formulas with n-3 and n-6 LCP in amounts typical for human milk fat results in similar fatty acid profiles of plasma and red blood cell membrane phospholipids as found during breast milk feeding.Conclusion Supplementation of formula with long-chain polyunsaturated fatty acids improves the LCP status of very low birth weight infants.     

The fatty acid composition of banked human milk and infant formulas: The choices of milk for feeding preterm infants

The fatty acid composition of 48 samples of banked human milk for preterm infants and four standard infants formulas available in Finland were analysed by capillary gas liquid chromatography. The banked milk was collected from mothers who had given birth 0–8 weeks previously. Saturated fatty acids accounted for approximately 50% of the fatty acids in both human milk and the formulas, while the relative content of monoenoic fatty acids tended to be higher in human milk than in the formulas. The relative content of 182n–6 was higher in the formulas (range 14.7%–23.2%) than in human milk (median 9.1%, range 6.3%–13.4%). Fat of banked human milk contained 0.9% and 0.7% polyunsaturated fatty acids with 20 and 22 carbon atoms (LCP), respectively, which is comparable to that of fresh mature human milk. In contrast, LCP could not be detected in any of the formulas. Conclusion: Banked human milk is a good source of LCP and offers a good alternative to LCP containing formulas.     

Effects of dietary long-chain polyunsaturated fatty acids on the essential fatty acid status of premature infants

The effect of different diets on the percentage content of long-chain polyunsaturated fatty acids (LCP; metabolites of linoleic and alpha-linolenic acids) in plasma lipids was studied in 29 premature infants on days 4 and 21 of life. Eleven infants were fed human milk which supplies LCP (1.7% of the fatty acids), 10 a commercially available milk formula without LCP, and 8 a new formula enriched with LCP of the omega-6 and the omega-3 series (0.5% LCP). LCP values in plasma lipids remained stable during the observation period in infants fed human milk. In contrast, LCP decreased markedly in plasma lipids of infants fed the conventional formula. Since the precursor fatty acids linoleic and alpha-linolenic acids were high in their diet and plasma, this finding indicates that premature infants have a limited capacity for LCP biosynthesis and may require their dietary supplementation. Infants fed the LCP enriched formula had significantly higher LCP proportions in plasma lipids than infants given the conventional formula, but less than infants fed human milk. Our results demonstrate that small concentrations of dietary LCP have marked effects on plasma lipid composition, particularly on phospholipids, suggesting that dietary LCP are preferentially channelled into structural lipids. We conclude that the essential fatty acid status of formula-fed premature infants can be improved by a supplementation of omega-6- and omega-3-LCP.Abbreviation LCP long-chain polyunsaturated fatty acids     

Effect of preterm formula with and without long-chain polyunsaturated fatty acids on the urinary excretion of F2-isoprostanes and 8-epi-prostaglandin F2alpha

BACKGROUND: The objective of this study was to evaluate the effect of conventional and long-chain polyunsaturated fatty acids (LCP)-enriched preterm formula on the endogenous formation of F2-isoprostanes and 8-epi-prostaglandin (PG) F2alpha as possible markers of lipid peroxidation in preterm infants during their first weeks of life. METHODS: In a prospective, randomized, double-blind study, infants received either formula enriched with LCP (n = 8), standard preterm formula (n = 7), or (expressed) breast milk (n = 8). Urine was sampled at study entry and after the study period of 3 weeks. The formation of F2-isoprostanes and 8-epi-PGF2alpha was evaluated by measuring the urinary excretion by gas chromatography-mass spectrometry. RESULTS: No differences in the urinary excretion of F2-isoprostanes and 8-epi-PGF2alpha were observed at the end of the study period. CONCLUSIONS: This result suggests that supplementation of a preterm formula with LCP for a period of 3 weeks does not stimulate lipid peroxidation in preterm infants.     

Serum cholesterol ester fatty acids in 7- and 13-month-old children in a prospective randomized trial of a low-saturated fat, low-cholesterol diet: the STRIP baby project

To evaluate changes that occur in serum cholesterol ester fatty acid composition during the transition from typical infant feeding to a more adult type of nutrition, this study compared the effects on serum cholesterol ester fatty acids of breast milk or formula at the age of 7 mo with effects caused by 6-mo dietary intervention in 137 children. The intervention [Special Turku coronary Risk factor Intervention Project for children (STRIP baby project)] aimed at a reduction of saturated fat intake to 10% of energy after the age of 1 y without purposefully influencing total fat intake. Nutrient intakes were calculated from 3-d food records. At the age of 7 mo, i.e. before dietary education began, milk type markedly influenced dietary and serum cholesterol ester fatty acid composition (mean serum cholesterol ester 16:0 in breastfed vs formula-fed infants, 13.7% vs 12.0%, respectively, p < 0.001; serum cholesterol ester 18:2n-6 50.6% vs 57.6%, p < 0.001). At the age of 13 mo the calculated fat intake of the intervention and control children differed markedly but serum cholesterol ester fatty acid compositions in all children resembled closely those measured in 7-mo-old breastfed infants, e.g. at the age of 13 mo the relative proportions of 18:2n-6 were 49.9% and 51.1% in previously formula-fed intervention and control children, respectively, and 50.3% and 50.1% in previously breastfed intervention and control children, respectively. In conclusion, serum cholesterol ester fatty acid composition reflected differences in dietary fat quality (breast milk or formula) at the age of 7 mo, whereas dietary intervention as applied in the STRIP baby project had only a minimal effect.     

Fatty acid composition in colostrum and mature milk from non-atopic and atopic mothers during the first 6 months of lactation

The fatty acid composition of total lipids was analysed in colostrum and mature human milk samples obtained at 1, 3, 4 and 6 months from 17 non-atopic and at 1 and 3 months from 17 atopic mothers. The relative levels of linoleic acid and α-linolenic acid increased up to 3 months after delivery and then declined. In contrast, the levels of their metabolites were higher in colostrum than in mature milk. The levels of dihomo-γ-linolenic acid, eicosapentaenoic acid, docosapentaenoic acid and docosahexaenoic acid were all lower in atopic than non-atopic mothers in milk samples obtained after 1 month of lactation (all p < 0:05). The ratio of total n -6 to n -3 long-chain polyunsaturated fatty acids (LCP) in milk at 1 and 3 months was higher in atopic than non-atopic mothers (all p < 0:05). Lower levels of the monounsaturated fatty acids (MUFA) were also observed in atopic mothers, as compared to non-atopic mothers. In the non-atopic mothers, the levels of individual n -6 LCP correlated and also correlated with n -3 LCP in colostrum and early mature milk ( r = 0:60-0.92, all p < 0:01). These correlations within n -6 and between n -6 and n -3 LCP were mostly absent in atopic mothers. The findings suggest that the LCP metabolism in human milk is disturbed in atopic mothers, as indicated by the lower relative levels of some LCP at 1 month, higher ratios of n -6 to n -3 LCP and poor correlations between the levels of the various compounds during the first 3 months of lactation.     

The effect of food supplements on the bioavailability of breast milk for premature infants--fecal fat and carbohydrate excretion

Faecal excretion of fat and carbohydrates was studied in 14 preterm infants fed on raw mother's milk (group I) or banked fortified human milk (group II) at days 7, 14, 21 and 28 of postnatal life: group I: n = 5; 31.0 +/- 2.0 weeks; 1954 +/- 441 g; group II: n = 9; 32.0 +/- 1.0 weeks; 1806 +/- 176 g. Mixtures of amino acids, peptides, minerals, dextrine and maltose were designed for fortifying banked human milk. There were no significant differences between faecal excretion of fat and carbohydrates in both feeding groups. The investigated human milk fortifier helps to realize the protein-energy ratio needed in preterm infants with well tolerable volumes of feeding and without stressing their limited digestive capacity.     

Breast milk levels of zinc and omega-6 polyunsaturated fatty acids and growth of healthy Chinese infants

AIM: To examine the concentrations of zinc and omega-6 polyunsaturated fatty acids (omega-6 PUFAs) in breast milk, the impact of zinc on omega-6 PUFA metabolism, and the growth rate of infants. METHODS: Forty-one mother-term infant pairs from a rural area of northern Beijing, China, who were 1 month (n = 18, group I) and 3 months (n = 23, group II) old and exclusively breastfed, were studied. The dietary records and the concentrations of zinc and omega-6 PUFAs in the milk of lactating women and the increase in weight and length of their infants during 1 and 3 postnatal months were analysed. RESULTS: The dietary intakes of mothers in the two groups were the same, i.e. high in carbohydrate and low in fat, protein and energy. The maternal zinc intake was 7.5mg/d and thus reached only 34.6% of the current Recommended Nutrient Intake (RNI). The levels of zinc and arachidonic acid (AA, C20:4 omega-6) in the milk of group I were significantly higher than those in group II. Furthermore, significant positive correlations were found between the concentrations of zinc and AA in the breast milk and between the level of milk AA and weight gain. CONCLUSION: Zinc may be a co-factor and essential for essential fatty acids (EFA) metabolism. Thus suboptimal zinc intake may cause EFA imbalance. Further studies of Chinese rural mother-infant pairs are necessary to determine whether zinc supplementation should be recommended when lactation exceeds 3 months.     

Effect of supplementation of preterm formula with long chain polyunsaturated Fatty acids on mineral balance in preterm infants

BACKGROUND: Incorporation of long chain polyunsaturated fatty acids (LCP) into formulas may interfere with mineral metabolism. We investigate mineral balance in preterm infants who were fed a formula with LCP. METHODS: Infants were randomized in a double-blind manner, 20 infants in each group, to receive a formula with LCP (F+LCP) or without LCP (F) for 30 days. Plasma levels (at the beginning and after 30 days) and nutritional balance (after 1 week) for Ca, P, Mg, Zn, and Cu were obtained for all infants. RESULTS: Groups were similar regarding birth weight, gestational age, weight, and corrected age at study start. During the 30-day study period, the groups had comparable milk intake and reached similar and satisfactory weight gains and longitudinal growth. Within each group, there was no change in plasma mineral concentrations over the course of the study, and there were no differences at each time point between groups. All values were within the normal range for age. No differences in mineral balance were detected between the F and F+LCP groups, with both groups demonstrating comparable intake, net retention, and fecal losses of each mineral. CONCLUSIONS: Adding a content of LCP blend similar to that of human milk to a preterm formula caused no disturbance in Ca, P, Mg, Zn, or Cu nutritional balance.     

Taurine supplementation of a premature formula improves fat absorption in preterm infants

The predominance of taurine (Tau) conjugated over glycine conjugated bile acids in infants fed human milk as opposed to those on formulas without added Tau could account for a more complete absorption of fat. Fifteen low birth weight infants were randomized to either Enfamil Premature or to Enfamil Premature added with 40 mumol/dl of Tau and compared to a third group made up of nine low birth weight infants fed their own mother's preterm milk. Formulas and human milk were fed according to tolerance and constituted the sole nutrition for 3 months. A metabolic study was carried out at 3 wk of age and control of growth was done periodically. Urinary Tau excretion (mumol/dl) was very low (p less than 0.001) in the group fed Enfamil Premature (0.3 +/- 0.1) when compared to the values obtained in infants supplemented with Tau (51.6 +/- 12.5) and in those on human milk (36.3 +/- 7.9). Infants supplemented with Tau (92.5 +/- 1.2) had a coefficient of fat absorption which was higher (p less than 0.05) than the unsupplemented group (87.5 +/- 7.9) and comparable to the human milk-fed group (91.6 +/- 1.4). The effect was more pronounced on the saturated fatty acids and varied inversely with their individual water solubility. There was no effect of Tau on nitrogen retention and growth was identical in the three groups. These data show that the addition of Tau to formula had no effect on growth but improved the absorption of fat especially saturated fatty acids which require higher concentrations of bile acids to form mixed micelles.     

Growth, fatty acid composition of plasma lipid classes, and plasma retinol and a-tocopherol concentrations in full-term infants fed formula enriched with Zω-6 and u-3 long-chain polyunsaturated fatty acids

Full-term infants fed formula without dietary long-chain polyunsaturated fatty acids (LCF) exhibit significantly lower plasma LCP values than breast-fed infants. We studied prospectively two groups of healthy full-term infants fed conventional infant formula without LCP (F, n = 10) or the same formula enriched with both ω-6 and ω- 3 LCP (LCP-F, n = 12). Anthropometric data were obtained and fatty acid (FA) compositions of plasma phospholipids, triglycerides and sterol esters as well as plasma retinol and α-tocopherol concentrations were determined at 5 days and 1, 2, 3 and 4 months of age. Gains in weight, length and head circumference did not differ between the two groups throughout the study period. Plasma FA values did not differ at 5 days of age. Between 1 and 4 months of age, plasma phospholipids of infants fed LCP-F consistently had significantly (p < 0.05) higher percentages of arachidonic acid (1 month: 9.7 (0.8) versus 7.0 (1.3) %wt/wt, 4 months: 8.7 (0.5) versus 6.6 (1.0) %wt/ wt, median (interquartile range), LCP-F versus F) and docosahexaenoic acid (1 month: 2.9 (0.5) versus 1.6 (0.3) %wt/wt; 4 months: 2.9 (0.4) versus 0.9 (0.3) % wt/wt). Plasma retinol and a-tocopherol concentrations did not differ between the two groups throughout the study. We conclude that this form of LCP enrichment of formula for full-term infants effectively enhances plasma LCP contents without detectable adverse effects. The potential effects on functional outcome need to be studied carefully in prospective clinical trials. Growth, infant formula, infant nutrition, long-chain polyunsaturated fatty acids, retinol, α-tocopherol     

Long-chain polyunsaturated fatty acids in human milk and brain growth during early infancy

Long-chain polyunsaturated fatty acids are essential for growth and development, and their crucial role in the development of the central nervous system and in retinal function has been the subject of many studies. As the balance between n-6 and n-3 fatty acids has to be optimal, their concentrations in the milk given to infants who are exclusively breastfed is of major importance. In this study, the composition of fatty acids in mothers' milk and the growth rate of the infant brain were analysed. Nineteen mother-term infant pairs from Stockholm, Sweden, were studied from birth to 1 mo and 3 mo of age, during which time the infants were breastfed exclusively. The dietary intake of the mothers was calculated and found to concur with the recommended daily dietary allowances of Swedish lactating women as regards energy, protein, fat and carbohydrates. The amounts of linoleic acid and alpha-linolenic acid in the diet were similar to those reported for European and North American women. The ratio between arachidonic acid (AA) and docosahexaenoic acid (DHA) in the milk from Swedish mothers is approximately the same as in the brain of infants, and was found to be positively correlated with the rate of gain of the occipito-frontal head circumference and of the calculated brain weight at 1 mo (p < 0.01) and 3 mo (p < 0.01) of age, respectively. However, further studies are needed to establish the exact requirements of AA and DHA for optimal growth and development during early infancy in exclusively breastfed infants.     

Fat intake and metabolism in Swedish and Italian infants

The purpose of the study was to compare fat intake and metabolism between two infant populations from Sweden and Italy given breast milk or similar infant formulas, but different weaning foods. Nutrient intake and fat metabolism were studied prospectively from 3-12 mo in 68 Swedish and 46 Italian healthy infants, breastfed or given similar infant formulas in combination with Swedish or Mediterranean weaning foods. Although nutrient intake and fat metabolism were similar at 6 mo, fat intake was lower at 12 mo in the Italian than in the Swedish formula group (p < 0.001). At 6 and 12 mo, higher dietary ratios of monounsaturated to saturated fatty acids (p < 0.01 and p < 0.001, respectively), and monounsaturated to polyunsaturated fatty acids (p < 0.05, p < 0.001) were found in the Italian than in the Swedish formula group. Total cholesterol and apolipoprotein B were lower at 6 mo (p < 0.01) in Italian breastfed infants than in Swedish ones. Lower concentrations at 6 and 12 mo of total cholesterol (p < 0.05, p < 0.05, respectively), apolipoprotein B (p < 0.05, p < 0.01) and triglycerides (p < 0.001, p < 0.01), and of apolipoprotein A1 (p < 0.01) at 12 mo, were found in the Italian formula group than in the Swedish one. In conclusion, plasma total cholesterol, apolipoprotein B and triglycerides were found to be lower in Italian infants than in Swedish infants during the second half of infancy. These findings may partly result from differences in fat compositions between Swedish and Mediterranean weaning diets and in total fat intake in late infancy. Differences in duration of breastfeeding and possibly in breast milk composition may also have influenced our results.     

NUTRITION IN LOW-BIRTH-WEIGHT INFANTS

ABSTRACT: Olegård, R., Gustafson, A., Kjellmer, I. and Victorin, L. (Department of Paediatrics I, University of Göeborg, Göteborg, Sweden). Nutrition in low-birth-weight infants. III. Lipolysis and free fatty acid elimination after intravenous adminstration of fat emulsion. Acta Paediatr Scand, 64: 745, 1975.–Triglyceride linoleic acid in a fat emulsion for intravenous administration (Intralipid) was used as a marker in an evaluation of fat metabolism in newborn low-birth-weight (LBW) infants. Qualitative data on fatty acids as well as quantification of triglycerides and free fatty acids were obtained by gas-liquid chromatography. Influences on these parameters after a single and after repeated injections of Intralipid revealed differences between low-birth-weight infants appropriate-for-date (AFD) (n =8) and those light-for-date (LFD) (n =5). The LFD exhibited in comparison with the AFD infants an impaired lipolysis of injected triglycerides and a retarded elimination from plasma of released free fatty acids. In LFD, in general, this resulted in triglyceride accumulation and low free fatty acid levels. Heparin facilitated plasma triglyceride lipolysis and free fatty acid elimination from the blood stream.