Effect of dietary intervention to reduce the n-6/n-3 fatty acid ratio on maternal and fetal fatty acid profile and its relation to offspring growth and body composition at 1 year of age.

BACKGROUND/OBJECTIVE: Evidence is accumulating that the long-chain PUFA (LCPUFA) are associated with offspring growth and body composition. We investigated the relationship between LCPUFAs in red blood cells (RBCs) of pregnant women/breastfeeding mothers and umbilical cord RBCs of their neonates with infant growth and body composition ≤ 1 year of age. SUBJECTS/METHODS: In an open-label randomized, controlled trial, 208 healthy pregnant women received a dietary intervention (daily supplementation with 1200 mg n-3 LCPUFAs and dietary counseling to reduce arachidonic acid (AA) intake) from the 15th week of gestation until 4 months of lactation or followed their habitual diet. Fatty acids of plasma phospholipids (PLs) and RBCs from maternal and cord blood were determined and associated with infant body weight, body mass index (BMI), lean body mass and fat mass assessed by skinfold thickness measurements and ultrasonography. RESULTS: Dietary intervention significantly reduced the n-6/n-3 LCPUFA ratio in maternal and cord-blood plasma PLs and RBCs. Maternal RBCs docosahexaenoic acid (DHA), n-3 LCPUFAs and n-6 LCPUFAs at the 32nd week of gestation were positively related to birth weight. Maternal n-3 LCPUFAs, n-6 LCPUFAs and AA were positively associated with birth length. Maternal RBCs AA and n-6 LCPUFAs were significantly negatively related to BMI and Ponderal Index at 1 year postpartum, but not to fat mass. CONCLUSION: Maternal DHA, AA, total n-3 LCPUFAs and n-6 LCPUFAs might serve as prenatal growth factors, while n-6 LCPUFAs also seems to regulate postnatal growth. The maternal n-6/n-3 LCPUFA ratio does not appear to have a role in adipose tissue development during early postnatal life.

Early neutral prebiotic oligosaccharide supplementation reduces the incidence of some allergic manifestations in the first 5 years of life.

BACKGROUND: A mixture of neutral prebiotic oligosaccharides has been shown to reduce the incidence of atopic dermatitis (AD) and allergy associated symptoms during the first 2 years of life. OBJECTIVE: To evaluate if this protective effect against allergy lasted beyond the intervention period until 5 y of age. METHODS: In a prospective, double blind, placebo-controlled fashion, healthy term infants at risk of atopy were fed either a prebiotic-supplemented (0.8 g/100 ml scGOS/lcFOS) or placebo-supplemented (0.8 g/100 ml maltodextrin) hypoallergenic formula during the first 6 mo of life. Following this intervention period, follow-up continued until 5 y of life. The present study evaluated (i) the cumulative incidence of allergic manifestations during 5 y, and (ii) the prevalence of allergic and persistent allergic manifestations at 5 y. Monitored allergic manifestations were AD, recurrent wheezing, allergic rhinoconjunctivitis and urticaria. RESULTS: Ninety-two children (50 in placebo group, 42 in intervention group) completed the 5-y follow-up. The 5-y cumulative incidences of any allergic manifestation and atopic dermatitis were significantly lower in the scGOS/lcFOS group (30.9, 19.1 %, respectively) compared to placebo group (66, 38 %, respectively) (p< 0.01 and< 0.05). Children in the scGOS/lcFOS group tended to have a lower incidence of allergic rhinoconjunctivitis, and allergic urticaria (4.8 vs 16% for both manifestations, p=0.08). There was no difference in the cumulative incidence of recurrent wheezing. With regard to the prevalences at 5 y, intervention group had significantly lower prevalence of any persistent allergic manifestation and rhinoconjunctivitis (4.8, 2.4 %, respectively) compared to placebo (26, 14 %, respectively) (p < 0.01 and =0.05). Prevalence of persistent AD tended to be lower in the intervention group (2.4 vs 12%, p= 0.09). Although intervention group had 75% reduction in the prevalence of persistent wheezing (4.8 vs 14 %), no significance was shown. CONCLUSION: Oligosaccharide prebiotics (scGOS/lcFOS), when started early in life have a protective effect against allergic manifestations in high risk infants. The protection lasts beyond infancy until 5 y of life, for AD and allergic rhinoconjunctivitis. Long-term follow-up studies in larger populations are warranted to evaluate the potential preventive effect of this mixture on asthma.

Immune-modulatory effects and potential working mechanisms of orally applied nondigestible carbohydrates.

Orally applied nondigestible carbohydrates (NDC) have been associated with immune-modulating effects and other health benefits. The effects of prebiotic carbohydrates have recently received much attention, but other NDC have been reported to induce immune modulation as well. Many different effects have been shown on parameters of innate and specific immunity, mostly in animal experiments or in vitro. Data from clinical trials are limited, but promising studies have reported beneficial effects on mucosal and systemic immunity in humans. NDC are fermented to various degrees by the intestinal microbiota. Therefore, immune-modulatory properties have often been attributed to microbiota-dependent effects, especially in the case of prebiotic NDC. However, some NDC have been reported to bind to specific receptors on cells of the immune system, suggesting microbiota-independent, immune-modulatory effects play a role as well. This review aims to provide an overview of the published immune-modulatory effects in vitro and in vivo induced by NDC such as fructans, galactooligosaccharides, beta-glucans, pectins, and resistant starch. In addition, issues related to the underlying mechanisms are discussed: interaction between bacteria, their metabolites and the immune system, as well as direct effects of NDC via lectin receptors.

Acidic oligosaccharides from pectin hydrolysate as new component for infant formulae: effect on intestinal flora, stool characteristics, and pH.

OBJECTIVES: To come even closer to the functional composition of human milk, acidic oligosaccharides (AOS) from pectin were added to well known neutral prebiotics (galacto-oligosaccharides (GOS) and long-chain fructo-oligosaccharides (FOS)). The effect of AOS and GOS/FOS/AOS on intestinal flora, stool characteristics as well as acceptance and tolerance was investigated. METHODS: Human milk contains 75% to 85% neutral and 15% to 25% acidic oligosaccharides. In this prospective, randomized, double blind study, a mixture of 80% neutral oligosaccharides (from long-chain galacto- and long-chain fructo-oligosaccharides) with 20% acidic oligosaccharides derived from pectin hydrolysis was investigated. Forty-six term infants were fed a standard formula supplemented with either maltodextrin as control (n=15), or with 0.2 g acidic oligosaccharides (n=16), or with the latter plus 0.6 g neutral oligosaccharides (mixture of galacto- and fructo-oligosaccharides; n=15). Fecal flora using plating technique and pH were measured. Stool characteristics and possible side effects (crying, vomiting, and regurgitation) were recorded. RESULTS: There was no difference in the bifidobacteria counts between the control and the group supplemented with acidic oligosaccharides alone (8.75+/-0.50 vs. 8.58+/-0.94 log colony forming units [CFU]/g stool). In infants fed the combination of acidic and neutral oligosaccharides, bifidobacteria were increased (9.61+/-0.70 log CFU/g stool; P<0.01). The same pattern was observed with lactobacilli. Stool consistency was softest in infants fed the complete oligosaccharide mixture, but also in those fed formula supplemented with acidic oligosaccharides alone, the stool consistency was significantly softer compared with the control group. Fecal pH increased in the controls, remained constant in acidic oligosaccharides alone, and decreased in the complete mixture of oligosaccharides group. CONCLUSION: There was no difference in growth, crying, vomiting, and regurgitation patterns between the groups. In summary, acidic oligosaccharides from pectin hydrolysate are well tolerated as ingredient in infant formulae but do not affect intestinal microecology.

Long-chain polyunsaturated fatty acids and neurological developmental outcome at 18 months in healthy term infants.

AIM: Previously, we found a beneficial effect of 2 mo supplementation of infant formula with long-chain polyunsaturated fatty acids (LC-PUFA) on neurological condition at 3 mo in healthy term infants. The aim of the present follow-up study was to evaluate whether the effect on neurological condition persists until 18 mo. METHODS: A prospective, double-blind, randomized control study was conducted. Three groups were formed: a control (CF; n = 169), an LC-PUFA-supplemented (LF; n = 146) and a breastfed (BF; n = 159) group. Information on potential confounders was collected at enrolment. At the age of 18 mo, neurodevelopmental condition was assessed by the age-specific neurological examination of Hempel and the Bayley scales. The Hempel assessment resulted in a clinical neurological diagnosis, a total optimality score and a score on the fluency of motility. The Bayley scales resulted in mental and psychomotor developmental indices. Attrition at 18 mo was 5.5% and non-selective. Multivariate regression analyses were carried out to evaluate the effect of type of feeding while adjusting for confounders. RESULTS: None of the children had developed cerebral palsy and 23 (CF: n = 8; LF: n = 10; BF: n = 5) showed minor neurological dysfunction. The groups did not show statistically significant differences in clinical neurological condition, neurological optimality score, fluency score, and the psychomotor and mental development indices. Multivariate analysis confirmed that there was no effect of type of feeding on neurological condition. CONCLUSION: This study indicates that the beneficial neurodevelopmental effect of 2 mo LC-PUFA supplementation in healthy term infants can not be detected at the age of 18 mo.

Oligosaccharides might stimulate calcium absorption in formula-fed preterm infants.

UNLABELLED: Among other components of human milk, oligosaccharides might contribute to the high efficiency of calcium absorption of breastfed infants. In adults, it can be shown that dietary oligosaccharides can improve calcium absorption. The present analysis was performed to evaluate a possible influence of dietary oligosaccharides on parameters of calcium metabolism in preterm infants. The concentrations of calcium and phosphorus in plasma and in spot urine samples as well as the plasma activity of the alkaline phosphatase were measured in preterm infants fed either a standard formula (n = 15) or a formula supplemented with dietary oligosaccharides (n = 15) at the end of a 4-wk feeding period. CONCLUSIONS: There was no influence of the different diets on the plasma concentration of calcium and phosphorus or on the plasma activity of alkaline phosphatase. In urine, there was a tendency towards higher calcium concentrations in the group fed the supplemented formula compared concentrations in the group fed the standard formula. The concentrations of phosphate were not significantly different and, as a consequence, there was a tendency towards a higher Ca/P molar ratio in the group fed the supplemented formula. The data indicate that the calcium absorption might be influenced by the dietary oligosaccharides. Thus, the possible effect of dietary oligosaccharides on calcium homeostasis should be included in the discussion concerning the consequences of the use of dietary oligosaccharides in preterm infant nutrition.

Long chain polyunsaturated fatty acid supplementation in infant formula and blood pressure in later childhood: follow up of a randomised controlled trial.

OBJECTIVE: To determine whether supplementation of infant formula milk with long chain polyunsaturated fatty acids (LCPUFAs) influences blood pressure in later childhood. DESIGN: Follow up of a multicentre, randomised controlled trial. SETTING: Four study centres in Europe. PARTICIPANTS: 147 formula fed children, with a reference group of 88 breastfed children. INTERVENTION: In the original trial newborn infants were randomised to be fed with a formula supplemented with LCPUFAs (n=111) or a formula without LCPUFAs but otherwise nutritionally similar (n=126). In the present follow up study the blood pressure of the children at age 6 years was measured. MAIN OUTCOME MEASURES: Systolic, diastolic, and mean blood pressure. RESULTS: 71 children in the LCPUFA supplementation group (64% of the original group) and 76 children in the non-supplementation group (60%) were enrolled into the follow up study. The LCPUFA group had significantly lower mean blood pressure (mean difference -3.0 mm Hg (95% confidence interval -5.4 mm Hg to -0.5 mm Hg)) and diastolic blood pressure (mean difference -3.6 mm Hg (-6.5 mm Hg to -0.6 mm Hg)) than the non-supplementation group. The diastolic pressure of the breastfed children (n=88 (63%)) was significantly lower than that of the non-supplemented formula group but did not differ from the LCPUFA formula group. CONCLUSIONS: Dietary supplementation with LCPUFAs during infancy is associated with lower blood pressure in later childhood. Blood pressure tends to track from childhood into adult life, so early exposure to dietary LCPUFAs may reduce cardiovascular risk in adulthood.

Dietary threonine reduces plasma phenylalanine levels in patients with hyperphenylalaninemia.

BACKGROUND: In order to achieve normal intellectual development, the plasma phe-nylalanine (PHE) levels of patients with hyperphenylalaninemia should not exceed toxic levels. This goal is usually accomplished by employing special diets in which the patient's protein intake is in the form of PHE-free mixtures of amino acids. There is evidence from our own observations in animals and a preliminary observation in patients with hyperphenylalaninemia that supplemental dietary threonine (THR) might decrease plasma PHE concentrations. METHODS: In this placebo-controlled crossover study, the effect of supplemental oral THR on the plasma amino acid concentrations of 12 patients with hyperphenylalaninemia was investigated. Before starting the first treatment period of this cross-over study, the patients were randomly assigned to one of two groups supplemented either with approximately 50 mg THR/kg per day or with a similar amount of maltodextrin as placebo. After a feeding period of 8 weeks and a wash-out period of 8 weeks, the supplements were crossed over and the study continued for an additional 8 weeks. Blood was obtained at the start and the end of each supplementation period. RESULTS: Dietary THR supplementation of approximately 50 mg/kg per day resulted in a significant decrease of plasma PHE levels ( P = 0.0234). There was a close positive correlation between plasma and urinary PHE concentrations ( P < 0.001) indicating that the lower plasma PHE levels in the THR supplemented patients were not caused by higher urinary excretion of PHE. CONCLUSIONS: The data of the present study show that oral THR supplementation has a clear plasma-PHE-reducing effect but they do not allow any conclusion about the mechanisms responsible for the observed effect. Although it seems attractive on the basis of the present data to use THR supplementation in patients with hyperphenylalaninemia, the mechanism of the observed effect should be clarified before introduction of such a treatment in these patients.

Significant utilization of dietary arachidonic acid is for brain adrenic acid in baboon neonates.

Dietary arachidonic acid (20:4n-6) utilization in-vivo for carbon recycling into de-novo lipogenesis and conversion to n-6 long chain polyunsaturates was investigated in baboon neonates using [U-(13)C]20:4n-6. Neonates consuming a formula typical of human milk received a single oral dose of [(13)C]arachidonic acid in sn-2 position of either triglyceride or phosphatidylcholine at 18-19 days of postnatal life. Neonate brain, retina, liver, and plasma were obtained 10 days later (28-29 days of life). Low isotopic enrichment (0.27-1.0%Total label) was detected in dihomo-gamma-linolenic acid (20:3n-6) in all tissues, but label incorporation into saturates or monounsaturates was not detected. In neonate brain and retina, 16% and 11% of total label was recovered in 22:4n-6, respectively. The relative contribution of dietary fatty acids to postnatal brain 22:4n-6 accretion can be estimated for dietary 20:4n-6 and preformed 22:4n-6 as 17% and 8%, respectively, corresponding to efficiencies of 0.48% and 0.54% of dietary levels, respectively. These results demonstrate in term baboon neonates that in vivo 1) 20:4n-6 was retroconverted to 20:3n-6, 2) 20:4n-6 did not contribute significantly to de novo lipogenesis of saturates and monounsaturates, and 3) the preformed 20:4n-6 contribution to brain 22:4n-6 accumulation was quantitatively a significant metabolic fate for dietary 20:4n-6.

Supplementation of a bovine milk formula with an oligosaccharide mixture increases counts of faecal bifidobacteria in preterm infants.

BACKGROUND: The establishment of a balanced intestinal microflora which may protect against infection is desirable for the preterm infant. OBJECTIVE: To investigate the effect of a preterm formula milk supplement consisting of oligosaccharides in similar proportions to human milk on the faecal flora and stool characteristics of preterm infants. STUDY DESIGN: To resemble the effect of human milk, an oligosaccharide mixture consisting of 90% galacto-oligosaccharides and 10% fructo-oligosaccharides was used to supplement a standard preterm formula at a concentration of 10 g/l. This supplemented formula was studied in 15 preterm infants, and the results were compared with those found in 15 infants fed a formula supplemented with maltodextrin as placebo. A group fed fortified mother's milk was investigated as a reference group (n = 12). On four days during a 28 day feeding period (1, 7, 14, and 28), the faecal flora was investigated, and stool characteristics, growth, and possible side effects were recorded. RESULTS: During the study period, the number of bifidobacteria in the group fed the oligosaccharide supplemented formula increased to the upper range of bifidobacteria counts in the reference group. The difference between the supplemented and non-supplemented groups was highly significant (p = 0.0008). The stool characteristics were also influenced by the supplement: the stool frequency after 28 days was significantly lower in the control group than in the oligosaccharide supplemented group (p = 0.0079) and the reference group (p < 0.0001). Over the study period, the stool consistency in the control group became harder, but remained fairly stable in the other two groups. There was no effect of the different diets on the incidence of side effects (crying, regurgitation, vomiting) or on weight gain or length gain. CONCLUSION: Supplementing preterm formula with a mixture of galacto- and fructo-oligosaccharides at a concentration of 10 g/l stimulates the growth of bifidobacteria in the intestine and results in stool characteristics similar to those found in preterm infants fed human milk. Therefore prebiotic mixtures such as the one studied may help to improve intestinal tolerance to enteral feeding in preterm infants.

An infant formula free of glycomacropeptide prevents hyperthreoninemia in formula-fed preterm infants.

BACKGROUND: Hyperthreoninemia is a well-known phenomenon in infants fed a whey protein-predominant formula. Sweet whey is commonly used for the production of these whey-predominant infant milk formulas. Sweet whey contains not only whey proteins but also the threonine-rich glycomacropeptide (GMP). In the current study, an experimental formula based on acid whey without GMP and a formula based on sweet whey with GMP (threonine content 17.2% higher than in the experimental formula) but otherwise with identical composition were tested with particular respect to threonine metabolism. METHODS: Fourteen preterm infants appropriate for gestational age were enrolled in this randomized cross-over study. After a feeding period of at least 7 days, the nutrition of each infant was switched to the other formula for the second feeding period. At the end of each feeding period, the concentrations of creatinine and amino acids in the plasma and in the urine were measured. RESULTS: In the plasma, the threonine concentration was significantly lower in the group fed the experimental GMP-free formula than in the group fed the sweet whey formula (P < 0.001). Renal excretion of all essential amino acids was generally very low and less than 2% of the intake, indicating that the kidneys had no marked homeostatic function with respect to plasma amino acid. The plasma concentrations of the threonine metabolites glycine and serine, and that of urea were not influenced by diet. CONCLUSION: Feeding a whey protein-predominant bovine milk produced from acid whey protein reduces significantly the hyperthreoninemia commonly found in formula-fed preterm infants. Thus, acid whey formulas should be recommended for feeding preterm infants.

Usefulness of short-term urine collection in the nutritional monitoring of low birthweight infants.

To establish adequacy of urine collection times shorter than 24h in the metabolic monitoring of low birthweight infants, we collected urine for 24 h in 39 LBW infants during the third and fourth week of life. All urine voidings over the 24-h period were separately collected, the volume of each sampling and the time of voiding were recorded, and 20% of the volume was removed for pooling. All individual and pooled samples were analysed for total nitrogen, urea and ammonia, alpha-amino nitrogen, creatinine, sodium, potassium, calcium and phosphorus, and for each compound the ratio to 1 mol creatinine was established. Individual sample results were "pooled" to obtain 3-, 6- and 12-h period excretion and than related to the 24-h excretion as measured in the pooled 24-h sample. As the volume of urine obtained in any 6-h collecting period depended on the time of sampling (06:00-12:00 h, 17.5+/-3.1% of total; 12:00-18:00 h, 31.6+/-5.1% of total; 18:00-24:00 h, 25.6+/-3.1% of total; and 0:00-06:00h, 25.3+/-2.9% of total), calculations were based on samples obtained from 18:00 to 06:00 h. The correlation between results of 3- and 24 h-collection periods was weakest, while results of the 6-h collection correlated highly with the total daily excretion (r = between 0.82 and 0.93 for the different compounds) and the correlation was only slightly better when the 12-h collection period was considered. The correlation between the mean molar substrate/creatinine ratio of all individual samples of a 24-h collecting period and the and total daily excretion of the respective substrate was weaker (r = between 0.46 and 0.76 for the different compounds) than the correlation between the results of a 6-h collecting period and the daily excretion is not as stable than in later life. The data indicate that 6-h urine sampling may be sufficient for metabolic monitoring of LBW infants. By contrast, urinary substrate/creatinine ratios are not good markers of the daily excretions of the respective substrate during the first weeks of life.

Docosahexaenoic and arachidonic acid absorption in preterm infants fed LCP-free or LCP-supplemented formula in comparison to infants fed fortified breast milk.

The absorption of long-chain polyunsaturated fatty acids (LCP) with particular respect to docosahexaenoic (DHA) and arachidonic acid (AA) has been studied in 39 very-low-birth-weight infants appropriate for gestational age after a 10-day feeding period. The infants were fed either a LCP-supplemented formula (n = 11), or a LCP-free formula (n = 11) or breast milk fortified with protein and carbohydrates to have similar protein and energy intakes as in the formula-fed infants (n = 17). Total fat content and fatty acid profile were measured in the human milk, the two formulas, and in the stool samples. After a 10-day feeding period, the fecal excretions of total fat, DHA and AA were measured during a 3-day balance period. The total fat apparent absorption rates were similar in all groups (84.1, 82.1 and 80.6% of intake, respectively). The DHA and AA intakes were significantly (p < 0.01) higher in the group fed the fortified breast milk than in the group fed the LCP-supplemented formula (DHA: 75.5 +/- 12.4 vs. 50.2 +/- 4.2 mg/72 h; AA: 45.5 +/- 5.8 vs. 30.2 +/- 2.7 mg/72 h). There was a tendency for lower apparent absorption rates for both LCPs studied in the group fed fortified breast milk when compared to the group fed LCP-supplemented formula (AA: 70.6 +/- 10.9 vs. 73.0 +/- 8.7% of intake, DHA: 69.0 +/- 10.6 vs. 74.2 +/- 9.5% of intakes, but the differences were not significant. As consequence of the different intakes, the net absorption of the two studied LCP fatty acids were significantly (p < 0.01) higher in the breast milk group than in the group fed the LCP-supplemented formula (DHA: 52.6 +/- 6.1 vs. 36.8 +/- 4.5 mg/72 h; AA: 31.4 +/- 3.1 vs. 22.4 +/- 2.3 mg/72 h). The data demonstrate that DHA and AA are absorbed from the studied LCP-supplemented formula at least as effectively as from human milk. The net absorption of these LCP depend on the amount of dietary intake, and seems to be influenced by the dietary LCP source.

Taurine supplementation prevents hyperaminoacidemia in growing term infants fed high-protein cow's milk formula.

Blood urea nitrogen (BUN) and plasma and urine amino acid concentrations were compared between three cohorts of healthy growing term infants who were breast-fed (BF) or randomly assigned to one of two formulas either taurine non-supplemented (FF) or taurine supplemented (FF + T). The infants were studied from 2 to 12 weeks of age. Weight gain and growth in length was normal and similar in all three feeding groups during the study interval. At 12 weeks BUN was significantly higher in the FF group than in the BF and FF + T groups, 16.5 mg/dl vs 7.0 and 7.3 mg/dl, respectively. Total plasma amino acids (FF group: 240.5 +/- 110.1 mumoles/dl; BF group 180.1 +/- 28.7 mumoles/dl; FF + T group: 182.3 +/- 89.4 mumoles/dl) and total essential amino acids (FF group: 89.8 +/- 37.3 mumoles/dl; BF group: 56.1 +/- 16.3 mumoles/dl; FF + T group: 53.0 +/- 24.2 mumoles/dl). The urine amino acid concentrations reflected the plasma levels in all groups. These results indicate that taurine supplementation to a high protein formula lowers BUN levels and the plasma urine amino acid concentrations by some yet unknown mechanism to concentrations similar to those found in breast-fed infants with a much lower protein intake.

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.

UNLABELLED: 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 alpha-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 alpha-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.

[Effect of the amino acid content of breast milk supplements on the amino acid profile in the plasma of newborn infants: human albumin in comparison with Eoprotin]. / Einfluss der Aminosäurezusammensetzung von Frauenmilchsupplementen auf das Aminosäureprofil im Plasma Frühgeborener: Humanalbumin im Vergleich mit Eoprotin.

The influence of amino acid composition of two human milk fortifiers (Eoprotin, Milupa AG, Germany, and human albumin) on plasma amino acid profiles was studied in 28 preterm infants after a 14-day feeding period. The concentrations of total essential amino acids increased in both feeding groups significantly if compared to the period without supplementation; only the concentrations of methionine and phenylalanine in the eoprotin group and those of threonine, methionine and isoleucine in the human albumin group did not increase significantly. However, only the concentrations of isoleucine (Eoprotin: 79 +/- 19 mumol/l; human albumin: 45 +/- 20 mumol/l, p < 0.001) and methionine (Eoprotin: 26 +/- 10 mumol/l, human albumin: 16 +/- 10 mumol/l, p = 0.014) were significantly different between the two feeding groups. There was a significant correlation between the differences in the serum concentrations and the ones of each essential amino acid concentration in the fortifiers (r = 0.951). The results indicate that the amino acid composition of human milk fortifiers must be taken into consideration to achieve optimal nutritional management of preterm infants.

[Post-conceptional age. Effect on protein requirements of premature infants]. / Das postkonzeptionelle Alter. Einfluss auf den Proteinbedarf Frühgeborener.

In 12 preterm infants (mean gestational age: 28.9 weeks; mean birthweight: 1230 g) (Group 1) the serum concentrations of urea and alpha-amino-nitrogen were studied during the 32nd and between the 36th and 37th week of post-conceptional age. In 9 preterm infants with a mean gestational age of 34.6 weeks (mean birthweight: 1860 g) (Group 2) the same parameters were estimated during the 36th or 37th week of postconceptional age. In all male infants (group 1: n = 6; group 2: n = 5) the excretion of nitrogen in urine and stools were measured during a 48 h balance period. During the study all infants were fed with human milk enriched with 3 g of a bovine human milk fortifier (Eoprotin, Milupa AG, Germany) per 100 ml human milk (mean protein intake: 3.4 g/kg.day; mean caloric intake: 132.5 kcal/kg.day). Despite the similar protein and energy intakes on all study days the serum concentrations of urea and alpha-amino-nitrogen were significantly higher during the 36th or 37th postconceptional week if compared to those found during the 32nd postconceptional week. This was accompanied by elevated renal excretion of total nitrogen due to an increased excretion of urea in the older infants. The nitrogen excretions in stools were low during both study periods. During the period 36 and 37 weeks of postconceptional age no differences could be found for all parameters studied between the both groups of different gestational ages. The data of the present study suggest that in preterm infants with postconceptional age of 37 weeks or more protein intakes of 3.4 g/kg.day and more may exceed the requirements of these infants. Thus, supplementation of human milk with protein is not necessary after the 37th week of postconceptional age if feeding volumes of 170 ml/kg.day or more are tolerated.

Influence of casein feeding to very-low-birth weight infants on the plasma amino acid concentrations and the renal amino acid excretion.

The response of plasma and urine amino acid concentrations to a casein formula and to supplemented human milk (both 1.4 gm protein/100 ml) was measured in very-low-birth weight (VLBW) infants (less than 1500 gm) at a postconceptional age of 36 and 40 weeks, respectively. A control group of infants was fed exclusively with fresh human milk (HM). Casein feeding to VLBW infants resulted in prefeeding plasma amino acid profiles and renal amino acid excretions which were not markedly different from those found in infants fed supplemented HM. In comparison with the control feeding group, the infants fed casein or supplemented HM responded with higher total plasma amino acid concentrations (114.4 +/- 33.7 vs 171.0 +/- 36.1 or 167.1 +/- 27.1 mumol/100 ml, respectively) reflecting the higher amount of protein provided by these two feedings. The critical amino acids (sulfur-containing and aromatic amino acids) were metabolized efficiently in infants fed the casein formula. Furthermore, a highly significant relationship (r = 0.795; p less than 0.001) between the plasma concentrations of tyrosine and valine was achieved in all infants independent of the food applied. This relationship could represent a control mechanism to prevent an inordinate influx of aromatic amino acids into the brain. In VLBW infants at a postconceptional age of 36-40 weeks, the metabolic and functional maturity reaches levels which were similar to those found in term newborns.

[Consequences of the composition of human milk for the nutrition of low-birth-weight neonates. III. Sodium and potassium]. / Konsequenzen der Zusammensetzung der Muttermilch für die Ernährung untergewichtiger Neugeborener. III. Natrium und Kalium.

The concentrations of sodium and potassium were studied in the 24 hour pooled human milk of 37 mothers delivered preterm (PTM) and of 19 mothers delivered at term (TM) from the second to the eighth postnatal day and in addition in the PTM during the third week of lactation. During the 4th week of life the sodium balance was estimated in 31 very low birth weight infants fed a human milk formula enriched with NaCl (n = 11) or NaH2PO4 (n = 11) and in 9 infants fed the same formula without supplementary sodium. The concentrations of sodium decrease significantly during the first week of lactation. The values are significantly higher in PTM than in TM during the first 3 days but decrease in both milks to values between 1 and 2 mmol/100 ml. The concentrations of potassium increase up to the 4th day of lactation and fall to approximately 1.5 mmol/100 ml at the end of the first week of lactation. There are no differences between PTM and TM. In all three balance groups the sodium balance are positive. But only in the infants fed a sodium-supplemented human milk formula the weight gain was adequate according to the protein and caloric intakes. No signs of a pathological sodium retention could be observed during the balance period. The data suggest that a sodium intake of more than 2.5 mmol/kg/day is necessary for optimal growth. Thus, the phosphorus supplementation should be done generally as 1 mmol NaH2PO4/100 ml human milk in very low birth weight infants.