Plasma Valine and Urinary C-Peptide in Breast-fed and Artificially Fed Infants up to 6 Months of Age

ABSTRACT. Plasma branched-chain amino acids and urinary C-peptide-creatinine excretion was determined at 3, 41/2 and 6 months of age in a group of 50 infants who were either breast-fed or artificially fed and selected at random. The average concentrations of valine in plasma and C-peptide in urine as well as the ratio between C-peptide and creatinine in urine were 2–3 times higher ( p < 0.01) in artificially fed as compared to breast-fed infants at all the ages studied. Plasma valine values correlated significantly with the urinary C-peptide/creatinine ratio ( r = 0.76, p < 0.01), which suggests that the enhanced insulin response induced by the artificial formula is related to its protein content.     

Plasma valine and urinary C-peptide in breast-fed and artificially fed infants up to 6 months of age

Plasma branched-chain amino acids and urinary C-peptide-creatinine excretion was determined at 3, 4 1/2 and 6 months of age in a group of 50 infants who were either breast-fed or artificially fed and selected at random. The average concentrations of valine in plasma and C-peptide in urine as well as the ratio between C-peptide and creatinine in urine were 2-3 times higher (p less than 0.01) in artificially fed as compared to breast-fed infants at all the ages studied. Plasma valine values correlated significantly with the urinary C-peptide/creatinine ratio (r = 0.76, p less than 0.01), which suggests that the enhanced insulin response induced by the artificial formula is related to its protein content.     

Faecal short chain fatty acids in breast-fed and formula-fed babies

Edwards CA, Parrett AM, Balmer SE, Wharton BA. Faecal short chain fatty acids in breast-fed and formula-fed babies. Acta Pædiatr 1994;83:459–62. Stockholm. ISSN 0803–5253
The intestinal flora of breast-fed infants differs from that of formula-fed infants. It is thought that this difference in flora may be one important reason why breast-fed babies suffer less from gastrointestinal disease. Differences in intestinal flora are reflected in the profile of faecal short chain fatty acids (SCFA). Very little is known about faecal concentrations of SCFA in babies fed breast milk or infant formula. In this study, faecal SCFA were measured in babies at two and four weeks of age who had been either exclusively breast fed or bottle fed from birth. There was no significant difference in total faecal SCFA concentrations between breast-fed and formula-fed babies when lactate was included. The formula-fed group, however, had less lactic acid and higher concentrations of propionic and n-buytric acids than breast-fed babies. Very few babies had significant levels of n-butyric acid, although this SCFA is believed to be important for the health of the colonic mucosa of adults.     

Macromolecular Absorption in Infants with Infantile Colic

ABSTRACT. Intestinal absorption of macromolecules, using human α-lactalbumin (α-LA) as a marker, was studied in breast-fed and formula-fed infants with infantile colic. Serum samples taken at 30 and 60 min after an intake of human milk were analyzed for α-LA by a competitive radioimmunoassay technique. Breast-fed infants with infantile colic had significantly higher s-α-LA levels compared with age-matched breast-fed control infants 0-1 month of age: median value 926 μg α-LA/I serum/I human milk/kg bodyweight (n= 11) versus 150 (n= 34); 1–2 months of age: 173 (n= 22) versus 31 (n= 16); 2–3 months of age: 132 (n= 8) versus 11 (n= 16). Similarly, formula-fed colicky infants had significantly higher s-α-LA levels than agematched formula-fed control infants 1-2 months of age: median value 126 (n= 12) versus < 10 (n= 14); 2–3 months of age: 156 (n= 11) versus < 10 (n= 10). The increased absorption of the macromolecule human α-lactalbumin in infantile colic suggests that the gut mucosa is affected in infants with infantile colic.     

EFFECTS OF DIET ON FATTY ACID COMPOSITION OF PLASMA AND RED CELL PHOSPHOGLYCERIDES IN THREE-MONTH-OLD INFANTS

Concentrations of the main lipid classes in plasma and the blood phosphoglyceride fatty acid patterns were measured in 3-month-old infants, fed breast-milk or an industrial manufactured formula. The levels of cholesterol and phosphoglycerides were in the normal range for young adults, but the triglyceride concentration was twice as high as in adults. There were no significant differences in the levels of the plasma lipids between the two groups, but the mean of the triglycerides was 25 % higher in the formula-fed group. The plasma and red cell phosphoglycerides had already assumed a fatty acid pattern of adult type. The concentration of the total polyenoic acids was significantly lower in the breast-fed group, the difference being entirely confined to the fatty acids of the linoleic acid series. Linoleic acid was 27% and 40%, respectively, lower in plasma phosphoglycerides and red cell lecithin of breast-fed than of formula-fed infants, but arachidonic acid did not show any significant difference in the two groups. The concentration of the fatty acids of the linolenic acid series was higher in the breast-fed infants. The blood lecithin ratio between the fatty acids of the linolenic acid series and the linoleic acid series was thus much lower in the formula-fed than in the breast-fed infants, the ratio being closely correlated with the dietary linolenate/linoleate ratio. Although the concentration of essential fatty acids was low in both plasma and red cell phosphoglycerides of breast-fed infants, there was no increase of 20: 3 (n – 9).     

Serum levels of bile salt-stimulated lipase and breast feeding

OBJECTIVES: Bile salt-stimulated lipase (BSSL) is present in the sera of healthy humans, may affect lipoprotein structure and composition, and reduce atherogenicity of oxidized LDL-cholesterol. Our aims were to examine serum levels of BSSL in breast- and formula-fed infants, and explore the influence of BSSL on serum lipid profile and oxidative status. METHODS: Infants (2-8 weeks old) were prospectively enrolled. Blood was drawn for serum levels of BSSL, total antioxidant status (TAS), and lipid profile. RESULTS: Serum levels of BSSL were similar in breast-fed (0.28 +/- 0.15 microg/l, n = 18) and formula-fed (0.31 +/- 0.09 microg/l, n = 15) infants, and were much lower than reported levels for adults. In breast-fed infants only, BSSL levels were correlated with LDL-cholesterol serum levels (r = -0.53, p = 0.04). Total cholesterol (119.2 +/- 34.3 mg/dl vs 97 +/- 27.2, and p = 0.05) and LDL-cholesterol serum levels (50.5 +/- 26.1 mg/dl vs 33.3 +/- 20.3, p = 0.05), were elevated in breast-fed compared with formula-fed infants, but TAS was similar in both groups (1.02 +/- 0.18 mmol/l and 0.98 +/- 0.12 mmol/l, respectively). CONCLUSIONS: Lack of difference in BSSL serum levels between formula- and breast-feeding, and lower BSSL levels in infants compared to adults, suggest that human milk does not contribute to BSSL serum levels.     

Milk protein intake in the term infant. II. Effects on plasma amino acid concentrations

The response of plasma amino acids to two bovine protein formulas with different protein content (1.6 and 1.2 g/100 ml containing 60% whey proteins and 40% caseins) was measured in term infants. These two groups of infants were compared with a group of infants that were breast-fed; all infants were fed ad libitum. Concentrations of threonine, valine and total branched chain amino acids reflected the amount of protein provided. Thus, the concentrations were higher in the higher protein formula infants from the second week of the study. In the low protein formula infants these amino acids were lower but differed from the infants on breast milk at eight and twelve weeks. Concentration of taurine was lower in the formula fed infants than they were in breast-fed infants at the end of the study. The valine/glycine ratio in the low protein formula group was lower than in the breast-fed group for the first four weeks of the study. After this time it was equal to that of the breast-fed group. These differences in plasma amino acid concentrations give further evidence that formulas now in common use for term infants provide a protein intake in excess of protein requirements after the first months of life.     

Tryptophan fortification of adapted formula increases plasma tryptophan concentrations to levels not different from those found in breast-fed infants.

Several recent studies have demonstrated significantly lower plasma total tryptophan concentrations in formula-fed than in breast-fed infants. We have measured preprandial plasma amino acid concentrations in infants breast-fed or fed a formula with a protein concentration of 1.57 g/dl and with a whey/casein ratio of 60:40 or a formula with a protein concentration of 1.37 g/dl and a whey/casein ratio of 40:60 and fortified with 10 mg/dl (15 mg/100 kcal) of tryptophan. Healthy term infants (10 per group) were either breast-fed from birth or randomly assigned to one of the two study formulas. At 4 and 12 weeks of age, anthropometric measurements were performed and blood samples were obtained. During the study period of 12 weeks, all infants showed normal growth (weight, length, and head circumference) and there were no statistically significant differences between the groups. The plasma concentrations of the essential amino acids phenylalanine, threonine, valine, and lysine were significantly lower in the breast-fed group than in both formula-fed groups. For tyrosine, methionine, leucine, histidine, isoleucine, and arginine, no significant differences could be found between the feeding groups. Concentration of total plasma tryptophan was significantly higher in the breast-fed group than in the group fed the tryptophan-unfortified formula, but no statistically significant difference could be found between the plasma tryptophan concentration in the breast-fed group versus the group fed the tryptophan-fortified formula. The results indicate that tryptophan fortification of adapted formula is necessary to achieve plasma total tryptophan concentrations similar to those found in breast-fed infants.(ABSTRACT TRUNCATED AT 250 WORDS)     

Take of rhesus-human reassortant tetravalent rotavirus vaccine in breast-fed infants

Rhesus-human reassortant tetravalent rotavirus vaccine at a titer of 4 x 10⁴ plaque forming units was evaluated for immmunogenicity in 194 6–8-week-old breast-fed Turkish infants. The vaccine was administered orally as a single dose following either a meal of breast milk or 30 ml of sodium bicarbonate-buffered soy milk formula. Four-fold or greater responses in rotavirus IgA ELISA antibody were detected in 62% and 65'% of the infants in the two groups, respectively ( p = 0.62). In a smaller comparison group of non-breast-fed infants, an IgA response was detected in 7 of 11 (64%) cases. In all vaccinees, a serological response was detected in 72% of the initially seronegative and 47% of the initially seropositive infants ( p = 0.001). We conclude that the take of rhesus-human reassortant tetravalent rotavirus vaccine in breast-fed infants is not compromised by breast feeding before vaccination. However, a higher titered preparation of the same vaccine may be required to improve overall immunogenicity in young infants, particularly in those with pre-vaccination rotavirus antibody.     

Effects of feeding regimen on blood glucose levels and plasma concentrations of pancreatic hormones and gut regulatory peptides at 9 months of age: comparison between infants fed with milk formula and infants exclusively breast-fed from birth

Little is known about the development of gut endocrine responses to food intake in infants after the first postnatal month. To examine this question and to ascertain whether the mode of feeding from birth affects postprandial endocrine changes, blood glucose levels and the plasma concentrations of 11 regulatory peptides were measured at 9 months of age before and after a breast feeding in 13 exclusively breast-fed infants and before and after a formula feeding in 7 infants weaned during the first 3 months of life. In the prefeeding concentrations of these substances, no significant differences were found between the two groups, with the possible exception of the plasma concentration of pancreatic polypeptide (p = 0.06). Postprandially, the responses were significantly smaller in the breast-fed infants, whose plasma concentrations of insulin, gastric inhibitory polypeptide, pancreatic polypeptide, and cholecystokinin were lower than in the formula-fed infants. In addition, the overall level of the insulin-glucagon ratio was lower (p = 0.03) in the breast-fed infants. A difference in the opposite direction was observed for plasma gastrin levels. No significant differences appeared between the groups for blood glucose, or plasma glucagon, vasoactive intestinal polypeptide, motilin, enteroglucagon, secretin, or neurotensin concentrations after feeding. It is concluded that at 9 months of age, the gut regulatory responses to milk feeding are of lower magnitude than during the neonatal period, but even at this age the response patterns still depend on the mode of feeding.     

PLASMA FREE AMINO ACID CONCENTRATIONS OF BREAST-FED INFANTS

ABSTRACT. Photometric determination of alpha-amino nitrogen in peripheral venous plasma and urine from 20 healthy, full-term infants, 1–5 months of age, showing normal growth and development during an uncomplicated lactation, revealed lower plasma levels than what has been found in adults, or 3.7±1.1 mg/100 ml, and a urinary excretion of 41 + 14 mg/24 hours. Ion-exchange chromatography of deproteinized peripheral venous plasma showed low valine concentrations, an increased glycine/valine ratio and high cystine and very high taurine levels when compared to the levels of healthy American infants of comparable ages fed 3-3.5 g/kg of cow-milk protein. The findings indicate that a formula based on cow-milk protein should optimally contain only 1.0–1.2 g protein/100 ml provided that it is "humanized" not only with regard to the lactalbumin/casein ratio, but also to the cystine and taurine content. The pattern of the plasma concentrations of free amino acids reported in the present investigation may be used as a normal reference for breast-fed infants.     

Effect of diet on the development of drug metabolism by cytochrome P-450 enzymes in healthy infants

Orally administered caffeine and dextromethorphan (DM) were used as pharmacologic probes to determine the effect of infant diet on acquisition of cytochrome P-450 (CYP) enzyme activity during the first 6 mo of life. The caffeine elimination rate constant (ke) was determined from serum, and concentrations of caffeine, DM, and their respective metabolites were measured in urine by high-performance liquid chromatography (HPLC). Caffeine ke was low at 2 wk and displayed a significant positive linear correlation with age (p < 0.001); increasing faster in formula-fed than in breast-fed infants (p < 0.001). This occurred concomitantly with a significant increase in urinary 1,7-dimethylxanthine (17X) and 1-methylxanthine (1X) (p < 0.001), suggesting faster acquisition of CYP1A2 activity in formula-fed infants. The urinary molar ratio of (17X + 1X)/caffeine and age strongly predicted caffeine ke (r2 = 0.65; p < 0.001) irrespective of feeding type. CYP3A4 activity, assessed as the molar ratio of 3-hydroxymorphinan/dextrorphan showed a similar marked increase with postnatal age (p < 0.001) that was also greater in formula-fed than in breast-fed infants. Formula feeding appears to accelerate maturation of caffeine and DM metabolism by increasing the activity of CYP1A2 and CYP3A4, respectively. Dietary modification of CYP activity may modulate drug biotransformation and thus alter systemic exposure to xenobiotics from a very early age.     

Antibody responses to parenteral and oral vaccines are impaired by conventional and low protein formulas as compared to breast-feeding

The vaccine response to poliovirus, diphtheria and tetanus toxoids in relation to protein intake was studied in infants, either breast-fed or given low (1.1 g/100 ml) or conventional (1.5 g/100 ml) protein formula. Serum, saliva and faeces antibodies were measured by the enzyme-linked immunosorbent assay. Neutralizing poliovirus antibodies were determined. The serum, saliva and faeces antibody responses in the two formula-fed groups of infants did not differ significantly, but for the low protein formula group which had significantly higher serum neutralizing titres to poliovirus after the second vaccine dose than the conventional formula group. However, the breast-fed group had significantly higher antibody levels than the two formula-fed groups together: serum IgG to diphtheria toxoid (p less than 0.01) and serum neutralization of poliovirus (p less than 0.001) at 21-40 months of age, saliva secretory IgA to tetanus (p less than 0.01), diphtheria toxoid (p less than 0.01) and poliovirus (p less than 0.05), as well as faecal IgM to tetanus toxoid (p less than 0.05) and poliovirus (p less than 0.01 and p less than 0.05) at 3 and 4 months of age. Breast-fed infants thus showed better serum and secretory responses to peroral and parenteral vaccines than the formula-fed, whether with a conventional or low protein content.     

Sleep organization and energy expenditure of breast-fed and formula-fed infants.

Sleep organization of infants may be influenced by differences in nutrient intakes from human milk and formula. Because sleep/awake and sleep stage patterns affect energy expenditure, we hypothesized that differences in sleep organization between breast-fed and formula-fed infants might account in part for differences in energy expenditure between feeding groups. Sleep stages and cycling of 4-mo-old breast-fed (n = 10) formula-fed (n = 10) infants were studied with simultaneous measurements of energy expenditure. EEG, electrooculogram, body movement by triaxial accelerometry, heart rate, and oxygen saturation were monitored during an overnight sleep session. Sleep stages, nonrapid eye movement (NREM), and rapid eye movement (REM) were determined. Behavioral observations were recorded by video tape and by a technologist. Oxygen consumption and carbon dioxide production were measured with an indirect calorimeter. Total number and duration of sleep cycles, REM latency, number of NREM and REM epochs, and duration of NREM epochs did not differ between feeding groups. Sleep latency was shorter (p < 0.05) and duration of REM epochs longer (p < 0.01) in the formula-fed group. Formula-fed infants spent a higher percentage of sleep time in REM compared with the breast-fed infants (42 versus 34%) (p < 0.003). Conversely, breast-fed infants spent a higher percentage of sleep time in NREM sleep and their heart rates during sleep were lower (114 versus 126 bpm; p < 0.01). Energy expenditure during REM sleep was 13.0 +/- 4.4% higher than during NREM sleep (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Looking for a relation between serum leptin concentration and body composition parameters in healthy term infants in the first 6 months of life

We carried out a cross-sectional study of 115 healthy infants, younger than 6 months old, exclusively breast-fed or formula-fed, to investigate correlations between circulating leptin concentrations and body composition measurements. Serum leptin was evaluated with radioimmunoassay, and body composition with bioelectrical impedance analysis. Multiple regression analysis showed a relationship between serum leptin and body mass index in the entire study population (P = 0.042). There was a significant negative relationship between serum leptin and phase angle (P = 0.006) in formula-fed infants. Serum leptin was positively related to subscapular skinfold thickness (P = 0.055) and negatively to reactance (P = 0.057) only in formula-fed infants, although the differences were just below significance. Serum leptin concentration was higher in breast-fed infants (P = 0.002), and was not correlated with body composition parameters. This study indicates that there is a relation between leptin and infant body composition in the first months of life, although the link needs to be explored further.     

Abnormalities in zinc homeostasis in young infants with cystic fibrosis

Low plasma zinc concentrations have been reported in approximately 30% of young infants with cystic fibrosis identified by newborn screening. The objective of this study was to examine zinc homeostasis in this population by application of stable isotope methodology. Fifteen infants with cystic fibrosis (9 male, 6 female; 7 breast-fed, 8 formula-fed) were studied at a mean (+/-SD) age of 1.8 +/- 0.7 mo. On d 1, 70Zn was administered intravenously, and 67Zn was quantitatively administered with all human milk/formula feeds during the day. Three days later, a 3-d metabolic period was initiated, during which time intake was measured and complete urine and fecal collections were obtained. Fractional zinc absorption, total absorbed zinc, endogenous fecal zinc, and net absorbed zinc were measured; fecal fat excretion was also determined. Fractional absorption was significantly higher for the breast-fed infants (0.40 +/- 0.21) compared with the formula-fed group (0.13 +/- 0.06) (p = 0.01), but with the significantly higher dietary zinc intake of the formula-fed group, total absorbed zinc was higher for those receiving formula (p = 0.01). In 1 infants with complete zinc metabolic data, excretion of endogenous zinc was twofold greater for the formula-fed infants (p < 0.05); net absorption (mg zinc/d) was negative for both feeding groups: -0.04 +/- 0.52 for breast-fed; -0.28 +/- 0.57 for formula-fed. Endogenous fecal zinc losses correlated with fecal fat excretion (r = 0.89, n = 9, p = 0.001), suggesting interference with normal conservation of endogenously secreted zinc. These findings indicate impaired zinc homeostasis in this population and suggest an explanation for the observations of suboptimal zinc status in many young infants with cystic fibrosis prior to diagnosis and treatment.     

Trace elements (copper, zinc, manganese, and selenium) in plasma and erythrocytes in relation to dietary intake during infancy

All determinations of copper, zinc, manganese, and selenium were performed with a flameless atomic absorption spectrophotometer. Seventy-three full-term infants aged 1 to 52 weeks were divided into three age groups. Each age group contained two subgroups, breast-fed and formula-fed. No statistically significant differences between formula-fed and breast-fed subgroups were found in regard to the levels of copper and zinc in plasma and erythrocytes. At 1 to 5 weeks of age, the manganese concentration of erythrocytes was higher in formula-fed than in breast-fed infants (p less than 0.001). This might be due to the high dietary intake of this element in the formula-fed subgroup. On the other hand, plasma selenium concentrations were significantly higher in breast-fed than in formula-fed infants of all ages (p less than 0.01 at 1 to 5 weeks and p less than 0.05 at 6 to 52 weeks). This suggests that selenium compounds are biologically more available for infant nutrition in breast milk than in formula.     

Protein Intake during Weaning

ABSTRACT. Metabolic responses to different feeding regimens during the weaning period have not previously been studied. In this study 30 healthy infants aged 4–6 months were divided into three feeding regimens with 10 infants in each. The regimens were: Human milk (HM-group), formula F₁ with 1.9g protein/100 ml (F₁-group) or formula F² with 2.7 g protein/100 ml (F₂-group). All infants received the same supplementary food and were fed ad libitum. Concentrations of serum urea were significantly higher ( p <0.001) in the formula groups as compared to the breast-fed infants throughout the entire study period. Serum albumin concentrations were within normal limits in the breast-fed infants indicating adequate protein nutritional status. There were no differences in the concentrations of creatinine and total nitrogen in urine between the artificially fed and the breast-fed infants at the beginning of the study (4 months), but at 6 months these concentrations were significantly higher in the formula-fed infants ( p <0.001). The results suggest that formulas now in common use during weaning provide amounts of protein which produce metabolic manifestations implying excessive protein intakes.     

Supplementation of an adapted formula with bovine lactoferrin. 2. Effects on serum iron, ferritin and zinc levels

Breast milk provides an excellent supply of most nutrients for newborn infants. Infant formulae should be nutritionally comparable to breast milk especially with regard to critical nutrients like iron and other trace elements. Infant formulae supplemented with various amounts of bovine lactoferrin were given to two groups of infants. These infants were compared with infants receiving unsupplemented formula and breast-fed infants. The effects of these diets on levels of haemoglobin, haematocrit, serum iron, ferritin and zinc were examined for a study period of 150 days. At birth, concentrations of iron, haemoglobin, haematocrit and zinc were comparable in all four feeding groups. The fact that the serum zinc level was not altered by lactoferrin supplementation appears to rule out an in-vivo effect of lactoferrin on zinc nutrition of infants. Ferritin levels of breast-fed infants were significantly higher than in non-supplemented formula-fed infants at day 30 and day 90. This difference was seen only at day 30, when comparing breast-fed infants to lactoferrin-supplemented formula-fed infants. Comparing the infants receiving formulae, the formula supplemented with the higher amount of bovine lactoferrin induced significantly higher serum ferritin levels compared to the unsupplemented formula at day 90 and day 150. These observations favour the idea that lactoferrin may be involved in iron absorption. Since this effect was pronounced only after 90 days, it has to be discussed as to whether this effect is a convincing argument for supplementing infant formulae with bovine lactoferrin.     

Whey predominant,whey modified infant formula with protein/energy ratio of 1.8 g/100 kcal: adequate and safe for term infants from birth to four months

BACKGROUND: Protein quality of breast milk is superior to that of formula proteins. To ensure that the protein intake is sufficient, starter formulas with conventional protein composition provide a protein/energy ratio of 2.2-2.5 g per 100 kcal to infants, which is much higher than that supplied with breast milk. Several studies have shown that formula-fed infants have higher plasma or serum urea concentrations than breast-fed infants do. We tested if feeding formulas with improved protein quality and a protein content corresponding to the minimum level that is consistent with international recommendations (1.8 g/100 kcal) allows patients to achieve normal growth and plasma urea concentrations. METHODS: Healthy term infants were enrolled into the study and were either breast-fed or randomly assigned to three formula-fed groups. Formula-fed infants received either a standard formula with a protein/energy ratio of 2.2 g/100 kcal, whereas the two other groups received formulas with a protein/energy ratio of 1.8g/100 kcal differing mainly by their source of protein. Subjects received breast milk or these formulas ad libitum as the sole source of energy from birth to four months of age in a controlled blind design (except for the breast-fed group). Anthropometric measurements (body weight and length) were obtained at birth, at 30, 60, 90, and 120 days. Energy and protein intakes were calculated from three-day dietary records. Blood was collected for biochemical measurements at 30, 60, and 120 days. RESULTS: No differences were found between the four feeding groups for weight- and length-gains or for body mass indices (BMI). No differences in energy intakes between the formula-fed groups could be found, whereas protein intakes were less in infants fed the 1.8 g/100 kcal formulas. Plasma urea levels of the infants fed the 1.8 g/100 kcal formulas were closer to those found in the breast-fed infants. CONCLUSION: Improvement of the amino acid profile permits a whey predominant starter formula with 1.8 g protein per 100 kcal to meet the needs of normal term infants during the first four months of life.