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     

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.     

Plasma lipid and apolipoprotein concentrations in full term infants fed formula supplemented with long-chain polyunsaturated fatty acids and cholesterol

Recent data indicate that supplementation of infant formula with ω-3 and ω-6 long-chain polyunsaturated fatty acids might offer developmental benefits for full term infants. We investigated biochemical consequences of feeding formula supplemented with egg lipids to provide long-chain polyunsaturated fatty acids and compared triglyceride, cholesterol, lipoprotein cholesterol (HDL₂-cholesterol, HDL₃-cholesterol, non-HDL-cholesterol) and apolipoprotein A-I, A-II and B concentrations in full term infants fed either conventional formula (n = 10) or a formula supplemented with ω-3 and ω-6 long-chain polyunsaturated fatty acids and cholesterol in amounts similar to those found in mature human milk (n = 12). At the age of 5 days, cholesterol, non-HDL-cholesterol and triglyceride concentrations were significantly higher in infants fed supplemented than in those receiving conventional formula. At the age of 30 days, triglyceride concentrations were significantly higher with supplemented than with conventional formula. Thereafter throughout the study, no significant differences were seen between the two groups. Conclusion Full term infants fed formula supplemented with ω-3 and ω-6 long-chain polyunsaturated fatty acids and cholesterol showed significantly higher plasma cholesterol and triglyceride concentrations than infants receiving conventional formula on day 5 and on days 5 and 30, respectively. Thereafter no appreciable effect of diet on plasma phospholipid, triglyceride, cholesterol, lipoprotein cholesterol and apolipoprotein concentrations were seen. Received: 13 March 1996 / Accepted: 21 October 1996     

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.     

Essential fatty acids in full term infants fed breast milk or formula.

To determine the biochemical effects of the fatty acid composition of plasma lipids, two groups of 10 healthy full term infants who were either exclusively breast fed or received a formula with similar contents of linoleic and alpha linolenic acids, but without long chain polyunsaturated (LCP) fatty acids, were studied prospectively. Plasma phospholipid, triglyceride, and sterol ester fatty acids were determined at the age of 2, 4, and 8 weeks by high resolution capillary gas chromatography. Breast fed infants maintained stable LCP fatty acid concentrations throughout the study. Formula fed infants had significantly lower median values of arachidonic acid (AA) at the ages of 2 (6.9 v 9.5% wt/wt) and 4 weeks (5.9 v 7.9%) and docosahexaenoic acid (DHA) at the ages of 4 (1.1 v 1.7%) and 8 weeks (1.0 v 1.7%) in plasma phospholipids. Median AA values in triglycerides were also significantly lower in the infants receiving formula at the ages of 2 (0.4 v 0.6%) and 4 weeks (0.3 v 0.6%). It is concluded that formula fed full term infants are unable to match the omega-3 and omega-6 LCP status of breast fed full term infants until at least two months after birth.     

Effect of type of early infant feeding on fatty acid composition of plasma lipid classes in full-term infants during the second 6 months of life

BACKGROUND: Previously, the authors found significantly higher arachidonic and docosahexaenoic acid values in plasma lipids in 2-month-old full-term infants fed human milk than in those receiving formula. This is the report of data obtained in full-term infants during the second half of the first year of life. METHODS: Healthy, full-term infants fed human milk (n = 12) or formula without preformed long-chain polyunsaturated fatty acids (n = 12) were investigated. Fatty acid composition of plasma lipid classes was determined by high-resolution capillary gas-liquid chromatography. RESULTS: Linoleic acid acid values in plasma phospholipids (18.5 [3.94] vs. 20.79 [4.34]) and gamma-linolenic acid values in plasma cholesteryl esters (0.17 [0.09] vs. 0.27 [0.20]) and triacylglycerols (0.27 [0.18] vs. 0.46 [0.27]) were significantly (P < 0.05) lower in breast-fed infants than in those receiving formula. Data are percentage weight by weight shown as median (range from 1st to 3rd quartile) for breast-fed vs. formula fed infants, respectively. In contrast, arachidonic acid values in plasma phospholipids (10.05 [2.90] vs. 7.03 [1.87]; P < 0.01), cholesteryl esters (7.54 [3.58] vs. 4.09 [1.81]; P < 0.05), and triacylglycerols (1.28 [0.84] vs. 0.80 [0.39]; P < 0.05), as well as docosahexaenoic acid values in plasma phospholipids (1.92 [0.36] vs. 1.02 [0.31]; P < 0.001), cholesteryl esters (0.39 [0.13] vs. 0.15 [0.13]; P < 0.001), and triacylglycerols (0.17 [0.17] vs. 0.09 [0.04]; P < 0.01) were significantly higher in infants fed human milk than in those receiving formula. CONCLUSION: Healthy, full-term infants fed formula without preformed dietary long-chain polyunsaturated fatty acids are unable to match the arachidonic and docosahexaenoic acid status of breast-fed infants even during the second half of the first year of life.     

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.     

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.     

A multicenter long-term safety and efficacy trial of preterm formula supplemented with long-chain polyunsaturated fatty acids

BACKGROUND: The tissue accretion of long-chain polyunsaturated fatty acids is compromised in infants born prematurely. Human milk contains long-chain polyunsaturated fatty acids, but most preterm infant formulas do not. The long-term effects of preterm formula supplemented with arachidonic acid and docosahexaenoic acid, in proportions typical of those in human milk, were therefore investigated. METHODS: In this double-blind, randomized study, 288 preterm infants received experimental formula (n = 77), unsupplemented (control) formula (n = 78), or human milk (n = 133) until 48 weeks postconceptional age (PCA). Term formula, without supplemental long-chain polyunsaturated fatty acids, was administered from 48 to 92 weeks PCA to formula-fed infants and to infants weaned from human milk. Anthropometric and fatty acid data were assessed by using analysis of variance. RESULTS: At 92 weeks PCA, no statistically significant anthropometric measurement differences were found except for midarm circumference, which was smaller in human milk-fed infants than in those fed formula. Phospholipid concentrations were similar in the experimental and human milk-fed groups, and docosahexaenoic acid levels were significantly greater than in the control group. The types and incidences of adverse events were similar among the feeding groups. CONCLUSIONS: The results of this study demonstrate the efficacy and long-term safety of preterm formula supplemented with long-chain polyunsaturated fatty acids.     

Impact of early dietary intake and blood lipid composition of long-chain polyunsaturated fatty acids on later visual development

BACKGROUND: In contrast to human milk, current infant formulas in the United States do not contain omega3 and omega6 long-chain polyunsaturated fatty acids. This may lead to suboptimal blood lipid fatty acid profiles and to a measurable diminution of visual function in developing term infants. The need for docosahexaenoic acid and arachidonic acid supplementation in the infant diet was evaluated in a double-blind, randomized clinical trial. METHODS: Healthy term infants were randomized to diets of (1) commercial formula, (2) docosahexaenoic acid-enriched formula (0.35% of total fatty acids), or (3) docosahexaenoic acid- (0.36%) and arachidonic acid- (0.72%) enriched formula. Eighty-seven infants completed the 17-week nutritional trial, and 58 were observed until 52 weeks of life. A reference group was exclusively breast fed for at least 17 weeks (n = 29). Outcome measures included electroretinographic responses, visual evoked potentials, and blood fatty acid analysis in infants at birth and at 6, 17, and 52 weeks of age. RESULTS: Commercial formula-fed infants had 30% to 50% lower content of docosahexaenoic acid in total red blood cell lipids during the 17-week feeding trial compared with breastfed infants. Significant differences persisted at the 1-year follow-up. Arachidonic acid content was consistently reduced in the commercial formula group by 15% to 20%. Infants fed long-chain polyunsaturated fatty acid-enriched formulas had docosahexaenoic acid and arachidonic acid blood lipid profiles resembling those of human milk-fed infants. Infants receiving this enriched formula had more mature electroretinographic responses than commercial formula-fed infants at 6 weeks of age. Human milk-fed and docosahexaenoic acid-enriched formula-fed infants had better visual acuity than commercial formula-fed infants at both 17 and 52 weeks of age. Early (17-week) fatty acid profiles in blood lipids were correlated with later (52-week) visual function development in study infants. CONCLUSIONS: Results from this clinical trial demonstrate that long-chain polyunsaturated fatty acid supplementation of formula in term infants produces blood lipid fatty acid profiles that are similar to those observed in breast-fed infants. This supplementation leads to better visual function later in life (i.e., 1 year of age) than that shown by infants fed commercial formula.     

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.     

Essential fatty acid metabolism and requirements for LBW infants

Humans are unable to synthesize linoleic acid (LA) (18: 2ω-6) and α-linolenic acid (LNA) (18: 3ω-3). Most formulas provide ample LA, yet infants are at risk for ω-3 deficiency unless they are fed human milk. Neonates born at 30 weeks received human milk or were randomized to three formulas: formula A, based on corn oil, similar to old commercial formula; formula B, based on soy oil supplied LNA; or formula C, a product similar to B with added marine oil to provide docosahexaenoic acid (22:6 ω-3). The fatty acids of plasma and red blood cells had marked diet-induced differences. The rod photoreceptor tests demonstrated higher threshold and decreased sensitivity in the ω-3-deficient infants. Visual acuity also showed improved function of the brain cortex in the human milk and group C infants at follow-up at 57 weeks. These results suggest that ω-3 fatty acids are needed for optimal development of visual function.     

The influence of dietary nucleotides on erythrocyte membrane fatty acids and plasma lipids in preterm infants

Objective : The objective of this study was to evaluate whether a regular formula for premature infants supplemented with nucleotides has any influence on plasma lipids and erythrocyte membrane fatty acids. Methods : Preterm infants fed either human milk supplemented with human milk protein (HM, n = 14), nucleotide-supplemented preterm formula (NF, n = 13), or a regular preterm formula (F, n = 13) were included in the study. The NF was supplemented with 18.2 mg cytidine monophosphate/1 (CMP), 7.0 mg uridine monophosphate/1 (UMP), 6.4mg adenosine monophosphate/1 (AMP), 3.0mg inosine monophosphate/1 (IMP) and 3.0 mg guanosine monophosphate/1 (GMP). Results : There were significantly higher concentrations of triglycerides (TG) in infants fed NF compared to those fed F (191.42 ± 79.58 vs 108.21 ± 43.73, p < 0.001, mean ± SD lipid concentrations, mg/100ml plasma). Infants fed F had significantly lower concentrations of total cholesterol (94.34 ± 11.71 vs 115.69 ± 39.29, p < 0.01) and TG in plasma (108.21 ± 43.73 vs 172.27 ± 68.19, p < 0.001, mean ± SD lipid concentrations, mg/100ml plasma) when compared to HM-fed infants. There were no significant differences in any of the erythrocyte membrane fatty acids and total long-chain polyunsaturated fatty acids (LC-PUFA) between NF and F during the study period (6 weeks). Furthermore, total LC-PUFA and docosahexaenoic acid (DHA) concentrations in red blood cell were not significantly different when infants fed NF were compared to those fed HM. In contrast, however, infants fed F had significantly lower concentrations of total n-3 LC-PUFA ( p < 0.01) and DHA ( p < 0.01) than those found in HM-fed infants. Conclusions : These results do not suggest an effect of nucleotides on the red blood cell LC-PUFA profile in preterm infants. However, the nucleotides may increase the concentrations of triglycerides in plasma.     

The Groningen LCPUFA study: No effect of short-term postnatal long-chain polyunsaturated fatty acids in healthy term infants on cardiovascular and anthropometric development at 9 years

Conflicting evidence exists on the effect of long-chain polyunsaturated fatty acid (LCPUFA) formula supplementation on cardiovascular health in term infants. It is known that LCPUFA supplementation does not affect infant growth, but long term outcome data are not available. The current study investigates whether 2 mo LCPUFA formula supplementation affects cardiovascular and anthropometric development at 9 y. A prospective, double-blind, randomized trial was performed in healthy term infants: a standard formula control group (CF, n = 169) and a LCPUFA-supplemented group [LF, n = 145; 0.45% (by wt) AA and 0.30% (by wt) docosahexaenoic acid (DHA)]. A breastfed group (BF; n = 159) served as reference. At the age of 9 y, systolic and diastolic blood pressure, heart rate, head circumference, weight, and height were measured. Univariate and multivariate analyses were performed; 63 to 79% of children were assessed. None of the cardiovascular or anthropometric measurements differed between the formula groups. Breastfed children had a marginally lower heart rate than formula-fed children, in particular compared with children fed control formula. Blood pressure and parameters of growth including BMI of breast and formula-fed children did not differ. In conclusion, the study suggests that short-term LCPUFA supplementation does not influence cardiovascular and anthropometric development at 9 y.     

A new breast milk supplement for preterm infants

Objective : To assess the effect of a new formula (Prenan), which contains n-3 and n-6 long-chain polyunsaturated fatty acids (LC PUFA) on the fatty acid profile of preterm infants.
Methodology : Plasma fatty acids were measured in 61 preterm infants at term by gas liquid chromatography. In 20 of these infants, paired samples were collected and changes in fatty acids with time analysed.
Results : Plasma docosahexaenoic acid (DHA) levels were higher in those who had been fed expressed breast milk (EBM) ±/or Prenan compared with those fed standard formula ± EBM, P <0.05. The plasma arachidonic acid (AA) levels of infants fed Prenan were not different to those fed EBM, both groups achieving higher levels than infants fed standard formula, P <0.05. Further, paired analysis demonstrated that DHA levels increased in infants changed from standard formula to Prenan to levels equal or higher than those of fully breast-fed infants ( P <0.01), whereas DHA levels remained unchanged with time in all other groups.
Conclusions : The fatty acid composition of Prenan enables preterm infants fed formula to have plasma DHA and AA levels similar to those of infants fed breast milk and consequently different to those of infants fed standard formula. Prenan is an appropriate supplement to breast milk for preterm infants in that it provides LC PUFA as well as additional phosphorus and protein without exposing the infant to intact cows milk protein.     

Noninvasive assessment of essential fatty acid status in preterm infants by buccal mucosal cell phospholipid analysis.

BACKGROUND: The dietary supply of long-chain polyunsaturated fatty acids is receiving increased attention since a linkage to infant growth and development has been reported. To avoid repeated blood collections for determination of long-chain polyunsaturated fatty acid status, the authors developed and evaluated a noninvasive method for analysis of buccal mucosal cell phospholipids. METHODS: Oral mucosal cells were gently collected with a soft cotton swab, buccal cell lipids separated by thin-layer chromatography, and fatty acid methyl esters of the phospholipid fraction prepared. Subsequently, the fatty acid methyl esters were analyzed by high-resolution gas chromatography. RESULTS: The method allowed reliable analysis from very small amounts of oral mucosal cells, and results were well reproducible. The intraindividual coefficients of variation in four samples of three subjects were less than 5% for both arachidonic and docosahexaenoic acid. Fatty acid composition was not altered by consumption of milk formula before and after sample collection. The method was applied in a clinical trial with preterm infants fed human breast milk or assigned by double-blind randomization to preterm formula with or without arachidonic and docosahexaenoic acid. Buccal mucosal cells were collected in infants less than 14 days of age and at the postconceptional ages of 52 weeks and 64 weeks. Dietary long-chain polyunsaturated fatty acids showed a lasting influence on buccal cell phospholipid composition. In the course of the study, arachidonic and docosahexaenoic acid decreased significantly in the nonenriched formula group, whereas stable or rising values were observed in the groups receiving breast milk or enriched formula. CONCLUSIONS: Buccal mucosal cell phospholipids are feasible for use as a noninvasive marker for long-chain polyunsaturated fatty acid status in preterm infants and yield reliable results. Dietary long-chain polyunsaturated fatty acids have a lasting influence on fatty acid composition of buccal cells in preterm babies.     

Feeding preterm infants a formula containing C20 and C22 fatty acids simulates plasma phospholipid fatty acid composition of infants fed human milk.

Thirty-four premature infants weighing less than 1500 grams at birth were fed preterm formula (formula), preterm infant formula manufactured to contain a balance of C20 and C22 omega 6 and omega 3 fatty acids within the range characteristic of human milk (LCPE-formula) or their mothers' expressed breast milk (EBM). Blood samples were obtained during the first week of life and after 28 days of feeding to determine the effect of feeding C20 and C22 omega 6 and omega 3 fatty acids on plasma lipids. Fatty acid analyses of red blood cell phospholipids indicated few differences between dietary treatment and age. Fatty acid content of plasma cholesterol esters indicated a high plasma cholesterol linoleate level for infants fed formula and a reduced content of C20 and C22 omega 6 and omega 3 fatty acids. For infants fed the modified formula (LCPE-formula) the levels of 20:4 omega 6, 20:5 omega 3 and 22:6 omega 3 were higher than observed for the formula group and similar to those observed for infants fed EBM. By the fifth week of life, feeding the modified formula resulted in plasma phospholipid levels of C20 and C22 omega 6 and omega 3 fatty acids similar to levels of C20 and C22 omega 6 and omega 3 fatty acids found in infants fed EBM and significantly higher than levels characteristic of infants fed formula. It is concluded that infants fed LCPE-formula illustrate an overall balance between C20 and C22 omega 6 to omega 3 fatty acids in the plasma similar to that characteristic of infants fed human milk.     

Requirements for long-chain polyunsaturated fatty acids in the preterm infant

Dietary long-chain polyunsaturated fatty acids have demonstrable beneficial effects on early development. The effects on neural development are of particular interest. Human milk is the best and only time-proven source of fat and essential fatty acids in the infant diet. Technologic procedures based on chemical and physical separation of the unsaturated fatty acids have permitted the isolation of concentrated sources of docosahexaenoic acid and arachidonic acid for clinical use. Virtually all infant formulas in developed countries have increased the levels of gamma-linolenic acid, and several manufacturers in Europe and in Japan have added docosahexaenoic acid, or docosahexaenoic acid plus arachidonic acid, or have also included gamma-linolenic acid in formulas for preterm and term infants. The efficacy of this practice for preterm infants seems fairly well established. The use of stable isotope methods to evaluate biosynthesis of long-chain polyunsaturated fatty acids from dietary precursors may help to better define optimal amounts and relationships of fatty acids in infant formula.     

Fatty acid balance studies in term infants fed formula milk containing long-chain polyunsaturated fatty acids

Long-chain polyunsaturated fatty acids (LCP) are thought to be required for optimal nervous system development in the newborn. A commercial milk formula containing LCP (Aptamil-LCP) with a fatty acid profile closely resembling breast milk, has recently been introduced for term infants. The absorption of fatty acids in term infants was examined in a double-blind randomized controlled trial comparing Aptamil-LCP ( n = 20) and standard Aptamil ( n = 20). Formula-fed newborn infants were studied from birth for 14 d. Fat balances (3 d) were performed from d 10. A 3-d stool collection was performed from d 10 in a parallel breastfed group ( n = 21). Plasma samples were taken on d 6. Median fat excretion (mg kg⁻¹) was 897.1, 615.0 and 355.2 with Aptamil, Aptamil-LCP and breastfeeding, respectively. The median total fat absorption coefficient in Aptamil-LCP-fed infants was higher than in those fed standard Aptamil ( p < 0:01). These findings were accounted for by differences in the excretion and absorption of long-chain saturated fatty acids (C14:0, C16:0 and C18:0). Higher fat excretion was associated with bulkier and firmer stools. Only trace amounts of LCP were detected in the stools of all groups. This accounted for less than 4% of dietary intake in Aptamil-LCP-fed infants. No differences in the utilization of LCP from Aptamil-LCP and breast milk feeding were apparent. Plasma phospholipid fatty acid composition data reflected differences in dietary LCP intake. Thus, PL LCP levels were highest in the breastfed infants and lowest in the Aptamil-fed infants, with values for the Aptamil-LCP-fed group falling in between.     

Visual acuity and cognitive outcomes at 4 years of age in a double-blind, randomized trial of long-chain polyunsaturated fatty acid-supplemented infant formula

BACKGROUND: While there is a large body of data on the effects of long-chain polyunsaturated fatty acid supplementation of infant formula on visual and cognitive maturation during infancy, longterm visual and cognitive outcome data from randomized trials are scarce. AIM: To evaluate docosahexaenoic acid (DHA) and arachidonic acid (ARA)-supplementation of infant formula on visual and cognitive outcomes at 4 years of age. METHODS: Fifty-two of 79 healthy term infants who were enrolled in a single-center, double-blind, randomized clinical trial of DHA and ARA supplementation of infant formula were available for follow-up at 4 years of age. In addition, 32 breast-fed infants served as a "gold standard". Outcome measures were visual acuity and the Wechsler Preschool and Primary Scale of Intelligence--Revised. RESULTS: At 4 years, the control formula group had poorer visual acuity than the breast-fed group; the DHA- and DHA+ARA-supplemented groups did not differ significantly from the breast-fed group. The control formula and DHA-supplemented groups had Verbal IQ scores poorer than the breast-fed group. CONCLUSION: DHA and ARA-supplementation of infant formula supports visual acuity and IQ maturation similar to that of breast-fed infants.