Bone mineralization in former very low birth weight infants fed either human milk or commercial formula

The bone mineral status of former very low birth weight infants previously fed fortified human milk was evaluated during the posthospitalization period. Anthropometric measurements, bone mineral content, bone width, serum calcium, phosphorus, and albumin concentrations, and alkaline phosphatase activity were evaluated at 10, 16, and 25 postnatal weeks. Infants were fed either commercial formula or unfortified human milk after their hospital discharge. At 16 and 25 weeks postnatally, human milk-fed infants (group HM) had lower bone mineral content (P less than 0.01), bone mineral content/bone width ratio (p less than 0.01), serum phosphorus concentration (p less than 0.03), and higher alkaline phosphatase activity (p less than 0.01) than commercial formula-fed infants (group CM). Growth was similar in both groups. Bone mineral content was correlated positively to serum phosphorus (r = 0.52, p less than 0.05) and inversely to alkaline phosphatase activity (r = -0.63, p less than 0.01) at 25 weeks postnatally. The use of serum biochemical markers, however, could account for only 44% of the variability in bone mineral content. The exclusive feeding of human milk to very low birth weight infants after hospital discharge may place them at risk for mineral deficiencies.     

Growth and plasma amino acid concentrations in very low birthweight infants fed either human milk protein fortified human milk or a whey-predominant formula

In a prospective, study involving 20 VLBW-infants (AGA), divided into two study groups of 10 infants, we have evaluated the effects on growth and metabolism of human milk fortified with ultrafiltrated human milk protein and a whey-predominant (whey/casein = 60/40) formula containing 2 g/dl of protein. The study was initiated at a mean age of 30 days when an oral intake of 180 ml/kg/d was tolerated and continued until a weight of 2 kg was reached. The protein intake in both groups was about 3.7 g/kg/d. All infants in both groups reached intrauterine rates of growth for the age, weight gain 18.0 g/kg/d, and length 1.2 cm/week. BUN, acid-base status, total protein and albumin were normal and similar in the two groups. Plasma levels of threonine, glycine, citrulline and methionine were significantly greater in the formula-fed infants. Taurine and proline had higher concentrations in the protein fortified human milk group. There was good tolerance of protein from both sources but the differences in plasma amino acid profiles suggest that the dietary protein quality in formulas for preterm infants must be further modified, if the goal of formula feeding is to achieve metabolic indices of protein metabolism similar to those found when human milk protein is used.     

Mineral homeostasis in very low birth weight infants fed either own mother's milk or pooled pasteurized preterm milk

As part of a randomised controlled study to assess the effect of pasteurization of breast milk on the growth of very-low-birth-weight infants, the longitudinal changes in serum calcium, phosphorus, alkaline phosphatase, 25-hydroxyvitamin D, and bone-gla-protein concentrations were investigated. Infants fed untreated own mother's milk grew more rapidly than those fed pasteurized pooled preterm milk and had higher serum alkaline phosphatase and lower phosphorus values. Serum calcium and 25-hydroxyvitamin D (25-OHD) concentrations were similar in the two groups. Despite the provision of 750 IU vitamin D daily from the 2nd week of life, serum 25-OHD values remained low in a number of infants in both groups, suggesting that either malabsorption of vitamin D or hepatic immaturity might be responsible for the persistently low values. Bone-gla-protein rose significantly after birth and was correlated with alkaline phosphatase values, but not with 25-OHD or phosphorus values. The study supports previous work that indicates that the low phosphorus content of breast milk is probably responsible for biochemical evidence of inadequate bone mineralization and that despite vitamin D supplementation, 25-OHD values do not rise adequately. Thirty-six infants were reexamined between 4 and 11 months after birth. The 25-OHD values had risen significantly in all infants except one who had vitamin D deficiency rickets.     

Amino acid concentrations in plasma and urine in very low birth weight infants fed protein-unenriched or human milk protein-enriched human milk

Preprandial plasma and urine amino acid concentrations were measured in 28 growing, very low birth weight, appropriate-for-gestational-age infants randomly assigned to either protein-unenriched (n = 14) or human milk protein-enriched (n = 14) human milk. The two groups of infants had similar birth weights (900 to 1500 g) and gestational ages (26 to 32 weeks). The study was initiated at a mean age of 19 days when the infants tolerated full feeding volumes and lasted for a mean time of 28 days. Mean protein intake values were 2.1 +/- 0.3 and 3.6 +/- 0.3 g/kg per day (mean +/- SD) and weight gain values were 26.6 +/- 7.4 and 35.1 +/- 3.6 g/day in the protein-unenriched and the protein-enriched groups of infants, respectively. Human milk protein enrichment resulted in significantly increased concentrations of all plasma amino acids except serine, taurine, and histidine. Most urine amino acid concentrations correlated with protein intake and with the plasma concentrations, suggesting that the effects of protein quality and quantity can be evaluated by measuring urinary amino acid concentrations alone, thereby making such studies less invasive. Infants fed protein-unenriched human milk had growth rates below the estimated intrauterine rate as well as low plasma and urine amino acid concentrations, indicating suboptimal protein intake levels. When the plasma concentrations of the essential amino acids in the protein-enriched infants from the present study were compared with concentrations found in the literature in fetal and umbilical cord plasma, both were found to be much higher.(ABSTRACT TRUNCATED AT 250 WORDS)     

Improved mineral balance in very low birth weight infants fed fortified human milk

Enhanced calcium and phosphorus retention was achieved in 16 very low birth weight infants (birth weight 1117 +/- 42 g, gestation 29 +/- 0.2 weeks) fed a preparation of fortified human milk augmented with calcium lactate and monobasic and dibasic phosphate salts. Measurements of growth and macronutrient utilization were similar to those obtained in a previous study of infants fed a preparation of fortified human milk that contained lower levels of calcium and phosphorus. However, unlike the relative hypophosphatemia, hypophosphaturia, and hypercalciuria noted in the infants in our earlier study, normal serum and urine phosphorus and urine calcium values were observed in this study. Postnatal calcium and phosphorus retentions correlated significantly with respective intakes, the absorption of fat, and the retention of nitrogen. The relationships among calcium and phosphorus intake and retention predict that 160 mg/kg/d and 94 mg/kg/d, respectively, must be fed to achieve retention equivalent to intrauterine estimates. Although postnatal retention of calcium and phosphorus may be increased to levels accumulated by the fetus, technical considerations for the preparation of a formula with sufficiently high levels of calcium and phosphorus must be resolved.     

Plasma amino acid patterns in very low birth weight infants during parenteral nutrition

Plasma amino acids were measured in eight very low birth weight infants (≤ 1000 gm) before and after infusion of parenteral alimentations with Freamine III. Significant elevation in serum threonine, valine, isoleucine, methionine, serine, proline, glycine and omithine was noted after twenty four hours of infusion. On the other hand, significant decreases in taurine and tyrosine levels were noted. Our study suggests that current solution is not optimal for premature neonates and the amount of protein administered during the first week in infants weighing ≤ 1000 gm should be decreased from the recommended 2.5–3.0 gm/kg/day.     

Nitrogen and fat balances in very low birth weight infants fed human milk fortified with human milk or bovine milk protein

The study was designed to compare two different human milk fortifiers in a group of very low birth weight (VLBW) infants by analysing nitrogen and fat balances, serum concentrations of alpha-amino-nitrogen, urea, and prealbumin as well as growth rates when human milk enriched with one of the two studied fortifiers was fed to the infants. Fortifier A contained different bovine proteins, peptides and amino acids and had an amino acid composition comparable to that of the nutritional available proteins in human milk, with carbohydrates, and minerals. Fortifier B was composed of freeze-dried skimmed human milk and minerals to achieve a similar macronutrient composition in both fortifiers.Eleven infants were fed with human milk enriched with fortifier A and 13 with fortifier B. After a 10-day equilibration period, a 3-day metabolic balance was performed. On the 14th day of the study blood was obtained preprandially for serum analysis and growth rates were estimated. The nitrogen absorption rate (93.8% vs 93.5%) as well as the retention rate (80.8% vs 78.5%) were no different between the groups. The fat absorption rate (92.3% vs 91.5%) as well as the weight gain (32.1 vs 31.1 g/day) were similar and there were no differences in the serum parameters studied. The results indicate that feeding VLBW infants with human milk enriched with a well-balanced bovine fortifier fulfil their nutritional requirements as well as diets composed exclusively of human milk protein.     

Assessment of proportional growth of very low birth weight infants fed banked human milk

Twenty appropriate (mean +/- S.D., gestational age (AGA): 29.9 +/- 1.5 weeks) and 15 small (GA: 34.6 +/- 2.4 weeks) for gestational age (SGA) very low birth weight infants fed banked mature human milk were studied until term for anthropometric parameters: midarm (MAC), chest (CC), head (HC) circumferences, triceps (TSKF) and subscapular (SSKF) skinfold thickness recorded at 15 and 60 s, dynamic skinfold (delta % SKF), muscle (AMA) and fat (AFA) areas, weight and length. In AGA infants, all the parameters at term were significantly lower in extrauterine (EUL) that in intrauterine life (IUL). At term the relative proportion of AFA to total arm area was increased in EUL compared to IUL both in AGA (25.87 +/- 3.8 vs. 23.26 +/- 1.27% respectively, P less than 0.01) and in SGA infants (21.89 +/- 4.63 vs. 18.81 +/- 3.9 respectively, P less than 0.05). SGA infants showed a similar growth in EUL compared to IUL, and a significantly lower AMA and AFA than in AGA infants in EUL. Although HC was in both infants below the 10th centile at term, the ratio weight/HC2 suggests a relative preservation of head growth in EUL compared to IUL (AGA: 20.72 less than 0.87 vs. 22.65 +/- 1.46 respectively, P less than 0.001; SGA; 20.82 +/- 1.16 vs. 21.62 +/- 1.86 respectively, NS). Delta %SKF were negatively correlated with post-conceptional age suggesting a loss of extracellular water in AGA (delta %TSKF: r = -0.287, P less than 0.02) and in SGA infants (delta %TSKF: r = -0.301, P less than 0.02; delta %SSKF: r = -0.316, P less than 0.02). An intrauterine model of discrimination between AGA and SGA infants does not apply to EUL. An equation was established in SGA infants with the best discriminant parameters giving a predictive post-conceptional age: post-conceptual age (PCA) (weeks) = 0.276 HC (cm) + 0.723 CC (cm) - 0.122 MAC (cm) + 0.5 TSKF (mm) + 10.173, (r = 0.867, P less than 0.001) allowing a clear discrimination between AGA and SGA infants. These results suggest that infants show quite different growth patterns between IUL and EUL both for AGA and SGA infants.     

Plasma amino acids in small preterm infants fed on human milk or formula.

Plasma amino acids were measured in 35 preterm infants, of whom 11 weighed less than 1000 g and 24 weighed between 1000 g and 1500 g at the time of sampling. Repeat samples were obtained in 18 at least seven days later. Seventeen infants were fed with preterm formula milk and 18 with expressed maternal breast milk at one to two hourly intervals during the study period. Formula fed infants gained weight faster than those fed on breast milk but there was little difference in amino acid patterns. Infants fed on breast milk were more likely to have concentrations of essential amino acids below the mid trimester fetal range than formula fed infants, but few infants in either feeding group had values above the fetal range. Those that did were equally distributed between both groups. Only two samples approached toxic concentrations, both in the group fed breast milk. The ratio of branched chain to aromatic amino acids was higher in the group fed on formula after correction for post conceptional age, implying that liver maturation may be accelerated by formula feeding. No correlations were found between plasma amino acid concentrations and nitrogen retention or metabolisable energy intake.     

Fortified preterm human milk for very low birth weight infants.

We studied the nutritional effects of two types of human milk fortifiers for very low birth weight infants. These studies suggest that fortified human milk provides nutritional advantages for very low birth weight infants. However, providing calcium and phosphorus with supplementation is necessary for the improvement of bone density.     

The calorie intake and weight gain of low birth weight infants fed on fresh breast milk or a special formula milk

The calorie intake and weight gain of 24 low birth weight (LBW) infants, <33 weeks gestation and <1500 g birth weight, was studied prospectively. Fourteen infants were fed on a commercially available LBW formula milk and ten were fed on their own mother's fresh unpasteurised expressed breast milk (EBM). The difference between the two feeding groups in the intake of milk and calories was not significant, but from the third week onwards those fed on the LBW formula gained weight faster. The mean (±SEM) weight increments for weeks 3–6 (inclusive) for LBW formula and EBM fed infants was 189.3 (±7.9) and 139.6 (±11.1) g/wk respectively (P<0.001).The LBW formula was well tolerated and is a suitable feed for LBW infants. However some babies thrived well on fresh EBM and so we are continuing to encourage mothers who wish, to breast feed their own preterm infants. When such infants fail to thrive it is appropriate to supplement with a LBW formula.     

Enhanced fecal excretion of selected immune factors in very low birth weight infants fed fortified human milk

The amounts of lactoferrin, lysozyme, total IgA, secretory IgA (SIgA), and specific SIgA antibodies to a pool of Escherichia coli O antigens were measured in 96-h collections of feces obtained from 28 very low birth weight infants, 28-30 wk of gestation, studied at 2.5 and 6 wk of age. Eighteen of these infants were fed their mothers' milk fortified with fractions of skim and cream derived from pasteurized, lyophilized, mature human milk (FM) and 10 infants were fed commercial cow's milk-based formula. The concentrations of these selected immune factors in the FM and formula also were measured. Specific SIgA antibodies to E. coli O antigens were detected in the feces of 90% of the FM-fed infants, but in none of the feces of the formula-fed infants. The feces obtained from FM-fed infants had markedly greater quantities of lactoferrin (p less than 0.001), lysozyme (p = 0.006), and IgA (p less than 0.001) than those of cow's milk formula-fed infants. The concentrations of total and secretory IgA were correlated significantly (r = 0.88, p less than 0.001) and 95% of total IgA was SIgA. The fecal concentration of specific SIgA antibodies to E. coli O antigens in FM-fed infants correlated with the concentration of these antibodies in their milk (p less than 0.001). However, there were no direct relationships between the milk concentrations or the infant's intakes of the other selected immune factors and the excretion of these factors in the feces.(ABSTRACT TRUNCATED AT 250 WORDS)     

Bone mineralization and mineral homeostasis in very low-birth-weight infants fed either human milk or fortified human milk

Abnormalities in bone mineral metabolism are frequently found in very low-birth-weight infants, especially if fed breast milk. To assess the efficacy of a breast-milk fortifier in the feeding of these very small infants, very low-birth-weight babies (between 1,000 g-1,500 g at birth) were randomly assigned to one of two groups on day 4 of life. The fortified group received the fortifier mixed in equal proportions with their own mother's milk, while the breast-milk group received only their own mother's milk. All infants received an oral vitamin D supplement of 750 IU/day. The study was continued until the infants weighed 1,800 g, at which stage breast feeding was encouraged. Thirty infants in the breast-milk group and 29 in the fortified group completed the study. Infants in the fortified group had significantly lower alkaline phosphatase values, a greater bone mineral content (BMC) and BMC/bone width ratio, and lower urinary calcium excretion than the breast-milk group at a weight of 1,800 g. At follow-up study 3 months after delivery, when most of the infants in both groups had been breast fed for at least 6 weeks, the breast-milk group's biochemical and BMC abnormalities were almost totally corrected and were now similar to those of the fortified group. Thus, the addition of the fortifier to breast milk during the first 4-6 weeks of life decreased the biochemical evidence of abnormal bone mineral homeostasis and increased BMC in very low-birth-weight infants. By 3 months of age, however, the breast-milk group had almost totally corrected its abnormalities.     

Energy balance in low birth weight infants fed formula of high or low medium-chain triglyceride content

We tested the effect on energy balance of the partial substitution of medium-chain for long-chain triglycerides in the diet of growing low birth weight infants. Fifteen infants were studied in a randomized double-blind crossover clinical trial in which each infant was fed each of two formulas, which were of equal gross energy and protein content but differed in fat composition. The high medium-chain triglyceride (MCT) formula contained medium- and long-chain triglycerides in a weight/weight ratio of 46:54; in the low MCT formula the ratio was 4:96. The hypothesis tested was that under conditions of equal gross energy intake the two diets would differ in their digestible and metabolizable energy contents and would produce differences in the infants' rates of energy expenditure and energy storage. Gross energy intakes averaged 562 and 555 kJ/kg/day (134 and 133 kcal/kg/day) with the high and low MCT formulas, respectively. With each diet, coefficients of energy digestibility (0.93) and metabolizability (0.91) were identical; the rates of energy expenditure were 262 (high MCT) and 265 (low MCT) kJ/kg/day (63 kcal/kg/day for both diets), and of energy storage were 246 (high MCT) and 239 (low MCT) kJ/kg/day (59 and 57 kcal/day). These differences were not significant. There were also no significant differences between the two diets in coefficients of nitrogen retention (mean 0.70) or in rate of weight gain (mean 21.5 gm/kg/day). The use of high MCT content in infant formula neither provided a nutritional advantage in energy digestibility or metabolizability nor resulted in an increased rate of energy expenditure or of energy storage.