Vitamin E status in preterm infants fed human milk or infant formula

Vitamin E status was assessed in 36 infants with birth weights less than 1500 gm who were assigned randomly to receive one of three sources of nutrition: milk obtained from mothers of preterm infants (preterm milk), mature human milk, or infant formula. Infants in each dietary group were further assigned randomly to receive iron supplementation (2 mg/kg/day) beginning at 2 weeks or to receive no iron supplementation. All infants received a standard multivitamin, providing 4.1 mg alpha-tocopherol daily. Serum vitamin E concentrations at 6 weeks were significantly related both to type of milk (P less than 0.0001) and to iron supplementation (P less than 0.05). Infants fed preterm milk had significantly higher serum vitamin E levels than did infants fed mature human milk, and both groups had significantly higher levels than did those fed formula. Ratios of serum vitamin E/total lipid were also significantly greater for infants fed human milks than for those fed formula. The addition of iron to all three diets resulted in significantly lower serum vitamin E levels at 6 weeks (P less than 0.05); however, only in the group fed formula was there evidence of vitamin E deficiency. Preterm milk with routine multivitamin supplementation uniformly resulted in vitamin E sufficiency in VLBW infants whether or not iron was administered.     

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.     

Nutrient balance studies in premature infants fed premature formula or fortified preterm human milk

This report compares fat, nitrogen, calcium, phosphorus, zinc, and copper absorption and retention data from 13 nutritional balance studies performed in 12 appropriate-for-gestational-age premature infants with birth weights less than or equal to 1,600 g fed a proprietary premature formula or their own mother's preterm human milk (PTHM) fortified with a powdered protein-mineral supplement. At the time of each balance study, each infant had a stable condition, was tolerating feedings, and was gaining weight steadily. Stool and urine were collected separately; doses of carmine red given 72 h apart were used to define dietary intake and the stool and urine collections. The balance studies were performed at an average age of 36 postnatal days. Both diets were found to support weight gain and nutrient retention at similar rates. Balance studies (n = 7) with premature formula demonstrated a weight gain of 16.8 +/- 5.2 g/kg/day, with a net fat absorption of 6.36 +/- 0.97 g/kg/day, net nitrogen retention of 427.9 +/- 47.1 mg/kg/day, net calcium retention of 95.0 +/- 14.1 mg/kg/day, net phosphorus retention of 56.7 +/- 5.9 mg/kg/day, net zinc retention of 208 +/- 903 micrograms/kg/day, and net copper retention of 26.4 +/- 30.8 micrograms/kg/day (mean +/- SD). Comparison balance studies (n = 6) with fortified PTHM demonstrated a weight gain of 17.2 +/- 7.1 g/kg/day, net fat absorption of 5.60 +/- 1.55 g/kg/day, net nitrogen retention of 366.0 +/- 84.0 mg/kg/day, net calcium retention of 82.2 +/- 10.8 mg/kg/day, net phosphorus retention of 58.6 +/- 5.9 mg/kg/day, net zinc retention of 685 +/- 363 micrograms/kg/day, and net copper retention of 67.3 +/- 37.2 micrograms/kg/day. These rates of weight gain and of fat, nitrogen, zinc, and copper retention approximate those of the third trimester of intrauterine life; only calcium and phosphorus retention approached the lower range of estimated in utero accretion.     

Urinary excretion of lactose and oligosaccharides in preterm infants fed human milk or infant formula

At present, not much is known about the absorption and metabolism of human milk (HM) oligosaccharides in term and preterm infants. We investigated the renal excretion of lactose and complex oligosaccharides in preterm infants fed HM ( n = 9, mean actual body weight 2290 g) or a cow's milk-based infant formula ( n = 9, mean actual body weight 2470 g). We found that the renal excretion of lactose in HM-fed infants was slightly lower than in formula-fed infants (14.0 ± 7.4 versus 20.4 ± 8.7 mg kg^-1 day^-1, mean ± SD). The excretion of neutral sugars deriving from oligosaccharides was similar in HM-fed and formula-fed infants (3.8 ± 2.1 versus 2.9 ± 0.9mgkg^-1 day^1-); the difference between means was not statistically significant. The separation and characterization of oligosaccharides by high-pH anion exchange chromatography with pulsed amperometric detection (HPAE-PAD) and subsequent analysis by fast atom bombardment-mass spectrometry (FAB-MS) revealed a more complex pattern in HM-fed infants compared to the formula-fed group. Lactose-derived oligosaccharides characteristic for HM (e.g lacto- N -tetraose, and lacto- N -fucopentaoses I and II) were excreted in HM-fed but not in formula-fed infants. These results indicate that nutrition has a significant impact on the oligosaccharide composition in urine of preterm infants.     

Indices of protein metabolism in term infants fed human milk, whey-predominant formula, or cow's milk formula

Relationships between intakes of amino acids and total nitrogen, and blood indices of protein utilization were studied in 37 term infants fed either human milk, whey-predominant formula, or cow's milk formula as the sole nutritional source for 8 weeks. Biochemical analyses of two-hour fasting blood samples, and intakes calculated using three-day dietary records and direct analyses of milk samples were used to evaluate these relationships. Intakes of total nitrogen were positively correlated with plasma valine, leucine, isoleucine, phenylalanine, and serum urea nitrogen concentrations (r = .46 to .62, P less than .01 to .001). Intakes of the four amino acids whose plasma concentrations were positively correlated with total nitrogen intakes plus four additional amino acids (threonine, tyrosine, histidine, and methionine) were correlated with their respective plasma concentrations (r = .41 to .74, P less than .01 to .001). These relationships have not been previously described in term infants. Compared with values in infants fed human milk, plasma concentrations of valine, phenylalanine, methionine, and serum urea nitrogen were elevated with whey-predominant formula and cow's milk formula feeding. Values for four additional amino acids (threonine, lysine, leucine, and isoleucine) were elevated with whey-predominant formula feeding. Data indicate that altering the whey-to-casein ratio and, thus, the amino acid pattern of formulas will not achieve the desired blood indices characteristic of human milk feeding without a reduction in the total nitrogen content of formulas.     

Growth and biochemical response of premature infants fed pooled preterm milk or special formula

This study compared growth of a group of very low birth weight infants fed a formula specifically developed for such infants (Formula) with another group fed expressed breast milk (EBM). The Formula contained 2.4 g/dl of protein (lactalbumin:casein ratio, 60:40); 4.1 g/dl of fat (40% medium-chain triglycerides); 8.8 g/dl of carbohydrates; and 81 kcal/dl, with more calcium, phosphorus, and electrolytes than are in human milk. Premature babies with birth weights between 1,200 and 1,500 g and gestational age less than 36 weeks were eligible for the study and were fed either pooled EBM or Formula until they reached a weight of 1,800 g. Twenty infants fed EBM and 19 infants fed Formula completed the trial. Weight gain was faster in the Formula-fed infants after a caloric intake of 100 kcal/kg/day was achieved (Formula 27.7 g/day vs. EBM 17.2 g/day; p less than 0.001). Time to reach 1,800 g was 27 days for the Formula group and 39 days for those on EBM (p less than 0.001). Increments in head circumference and skinfold thickness were also greater in the Formula-fed group. Laboratory studies in the two groups of infants showed higher alkaline phosphatase levels, which were not due to vitamin D deficiency, in the EBM-fed infants.     

Zinc homeostasis in premature infants does not differ between those fed preterm formula or fortified human milk

The objectives of this study were to compare zinc homeostasis in premature infants enterally fed with either preterm infant formula or fortified human milk; to examine interrelationships of variables of zinc homeostasis; and to examine the findings in relation to estimated zinc requirements of preterm infants. Zinc homeostasis was studied in 14 infants (8 male), with mean gestational age of 31 wk and birth weight appropriate for gestational age, who were exclusively fed either preterm formula (n = 9) or own mother's milk with human milk fortifier (n = 5). Zinc stable isotopes were administered intravenously ((70)Zn) and orally as an extrinsic label ((67)Zn) over multiple feeds for determination of fractional absorption by dual isotope tracer ratio in urine; endogenous fecal zinc was determined by isotope dilution; and exchangeable zinc pool (EZP) size was estimated from linear regression of log-transformed urine (70)Zn enrichment data. Results indicated no significant differences in the variables of zinc homeostasis between the feeding groups; data for all subjects were thus combined. Mean (+/- SD) fractional absorption was 0.26 +/- 0.07; net absorbed zinc 0.43 +/- 0.25 mg/d (0.31 +/- 0.19 mg/kg/d). Mean EZP was 20 +/- 10 mg/kg, and was positively correlated with total absorbed zinc and with net absorbed zinc. Feeding type and total absorbed zinc were significantly related to daily weight gain (p = 0.003). Current zinc intakes from fortified human milk or formula are associated with acceptable weight gain, but whether the observed net zinc absorption was optimal in the human milk group cannot be definitively determined from these data.     

Nitrogen and mineral balance in preterm infants fed human milks or formula

Growth as well as nitrogen, calcium, sodium, and potassium balances were evaluated in 16 preterm infants weighing less than 1,600 g at birth, who were fed either their mother's milk, donated mature human milk, or standard commercial formula. Birthweight, gestational age, age of balance, and energy and fluid intakes were similar between groups. There were no differences between groups in the rate of growth. The infants fed their mother's milk (obtained 11-30 days into lactation) demonstrated nutrient balance similar to infants fed mature human milk. Infants fed standard commercial formula demonstrated significantly greater intake and retention of calcium compared to either human milk group. Infants fed either their mother's milk or mature human milk demonstrated net nitrogen and calcium retention below estimates of fetal nitrogen and calcium accretion. Infants fed standard formula demonstrated retentions that more closely approach the fetal estimates. This study did not demonstrate an advantage to feeding premature infants their mother's milk when compared to the feeding of mature donor milk.     

Measurement of bone mineral density by dual energy X-ray absorptiometry in preterm infants fed human milk or formula

Bone mineralization of healthy preterm infants fed human milk were compared with that of similar fed preterm formula. Bone mineralization was studied by dual energy X-ray absorptiometry in 43 preterm infants divided into two groups; 21 preterm infants were fed with maternal breast milk and 22 preterm infants with a preterm formula containing 70 mg calcium and 35 mg phosphorus per decilitre. Conclusion Preterm infants fed breast milk had lower bone mineral density than the preterm formula-fed group. Fortifying preterm human milk with calcium and phosphorus will improve bone mineralization in preterm infants. Received: 26 November 1996 and in revised form: 26 August 1997 / Accepted: 9 September 1997     

Whole body protein turnover and urea production of preterm small for gestational age infants fed fortified human milk or preterm formula

OBJECTIVES: To investigate protein metabolism and urea production in preterm small for gestational age neonates fed a preterm formula or fortified human milk. METHODS: Ten preterm small for gestational age neonates were fed either their own mother's milk fortified with a powdered protein mineral supplement or a special preterm formula. Protein metabolism was determined using constant steady-state infusion of L-[ring-2H5]phenylalanine and L-[1-13C]valine. Urea production was determined from steady-state [13C]urea kinetics. RESULTS: Mean protein intake was 24% higher in the preterm formula group than in the fortified human milk group. No differences in protein turnover, synthesis and breakdown were observed between the two groups, but protein accretion was 71% to 79% higher in the preterm formula group than the fortified human milk group. Urea production rates were not different in the two groups. There was a strong negative correlation between urea production and protein accretion calculated from phenylalanine kinetics but not when calculated from valine kinetics. CONCLUSIONS: Preterm formula and fortified human milk appear equally well tolerated by preterm small for gestational age neonates, but protein accretion was higher in the preterm formula group. In preterm small for gestational age infants, both phenylalanine and valine kinetic methods can be used to accurately determine protein metabolism.     

Food allergy in preterm infants fed human milk

In 80 preterms aged 9-24 months (mean age: 15.9) and in 80 sex- and age-matched full-terms the frequency of atopic diseases and of positive skin tests to 8 food and 6 inhalant allergens was determined. The two groups did not differ as to overall percentages of cutipositive subjects and patients with atopic diseases. In particular, frequencies of positive skin tests to foods and of atopic dermatitis (the peak prevalence of which occurs early in infancy) were similar in preterm (16.2 and 7.5%, respectively) and full-term (13.7 and 5.0%, respectively) infants. We suggest that preterm infants fed human milk are not at increased risk of developing food allergy and related diseases and that the absorption of antigens through the immature intestine does not seem to favor the development of an IgE sensitization to foods.     

Fecal cholesterol excretion in preterm infants fed breast milk or formula with different cholesterol contents

In 44 very low-birth-weight infants, fecal cholesterol excretion was measured and in 29 other infants serum total cholesterol concentrations in response to different cholesterol intakes were studied. The infants received fortified breast milk (mean cholesterol content 15.3mg/dl) or were fed either a standard preterm formula (cholesterol content 5.5mg/dl) or the same formula but with a modified lipid composition (long chain polyunsaturated fatty acid concentration closely related to breast milk fat) and 30 mg of cholesterol/dl. In the group fed the high cholesterol formula, fecal cholesterol excretion was significantly higher (35.5mmol/kg/day) than in the groups fed breast milk or the standard formula (20.1 and 18.2mmol/kg/day). Cholesterol balance in the group fed the high cholesterol formula (21.8mg/kg/day) was significantly higher than in the group fed breast milk (+8.6mg/kg/day). In the infants fed the low cholesterol formula the balance was negative (-7.7 mg/ kg/day). Serum concentrations of total cholesterol were similar in the groups fed breast milk or the high cholesterol formula (3.47 and 3.51 mmol/1), but significantly higher than in the group fed the low cholesterol formula (3.15 mmol/1). The data suggest that preterm infants are able to regulate a higher cholesterol intake than during breast feeding by increasing fecal cholesterol excretion as well as decreasing endogenous synthesis.     

Selenium status of New Zealand infants fed either a selenium supplemented or a standard formula

Objective: New Zealand soils are deficient in the essential micronutrient, selenium. New Zealand infants have low selenium levels at birth and experience a further decline if fed cows milk based formula. This study examined the selenium status of infants fed with a new commercially available selenium supplemented formula.
Methodology Forty-four newborn infants, whose mothers wished to formula feed, were randomized in an open controlled trial to be fed a commercially available selenium supplemented cows milk formula (containing 17 μg Se/L) or an unsupplemented formula (containing 4.6 μg Se/L). Cord, 1 and 3 month blood samples were obtained for selenium status (plasma and red cell selenium and glutathione peroxidase) and thyroid function.
Results Mean plasma selenium and glutathione peroxidase values were significantly higher in supplemented than unsupplemented infants at 1 month (unpaired t -tests; P <0.0001 and P = 0.001 respectively) and 3 months ( P <0.0001 and P = 0.0005). Analysis within treatment groups between time points (paired t -tests) showed that selenium supplementation prevented the fall in plasma selenium from birth to 1 month seen in unsupplemented infants and was associated with a rise in levels between 1 and 3 months ( P = 0.002).
Conclusions Supplementing cows milk formula with selenium to replicate the levels found in breast milk is nutritionally sound. Feeding from a few days of age with a formula containing 17 μg Se/L in infants with low selenium status at birth is sufficient to cause a rise to 80% of adult levels at 3 months of age.     

Nutrient balance, energy utilization, and composition of weight gain in very-low-birth-weight infants fed pooled human milk or a preterm formula

Growth, protein, and energy balances were studied in two groups of very-low-birth-weight premature infants fed pooled pasteurized human milk (HM) or a preterm formula (PF). Each infant was studied at 33 and 36 weeks gestational age with a combined technique of nutrient balance and indirect calorimetry measurement. Weight and length gains were higher with PF than with HM, but head circumference growth was similar with both milks. Although the volume of milk given was lower, energy intake was higher with PF than with HM in both studies (126 to 130 vs 103 to 109 kcal/kg/day). Percentage of energy absorbed was better with PF than with HM (94% vs 84%) at 33 weeks, and similar (95%) with both milks at 36 weeks. Energy expenditure, which had increased from 33 weeks to 36 weeks, was higher with PF than with HM (57 to 63 vs 46 to 52 kcal/kg/day) during both studies. Energy retention accounted for about 50% of energy absorbed with both milks, but was higher with PF than with HM (60 vs 40 to 50 kcal/kg/day) in both studies, and resulted in fat accretion well above that seen during intrauterine growth for both milks in both studies. Protein intake was higher with PF than with HM (3.1 vs 2.4 gm/kg/day) in both studies, giving a protein accretion similar to the intrauterine accretion with PF (2.2 gm/kg/day), but lower with HM. Our results suggest that the nutritional value of pooled pasteurized human milk for VLBW infants should be reconsidered, especially because of its low protein content, and that energy density of preterm formulas must be questioned in view of elevated fat deposition.     

Selenium in German infants fed breast milk or different formulas

At birth and at 4 months of age, selenium (Se) values of 129 term infants on three different diets were determined: 50 infants were breast fed (HM), 44 received formula based on cow's milk (F) and 35 were fed "hypoallergenic formula" (PHF) (partially hydrolysed whey protein). The Se status of a group of twins (n = 12) fed "hypoallergenic formula" was compared with the respective group of singletons. All infants had low plasma Se values during early infancy. The plasma Se of breast-fed infants remained stable (plasma Se 438 ng/ml at birth and at 4 months), whereas plasma glutathione peroxidase (GSH-Px) decreased (birth: 10729 U/l; 4 months: 6211 U/l). The formula-fed infants showed a reduction in plasma Se levels from birth to 4 months (3810 ng/ml and 299 ng/ml, respectively). The decrease was even more pronounced in infants fed the "hypoallergenic formula". This group presented the lowest Se values (plasma Se 399 ng/ml at birth; 206 ng/ml at 4 months). Renal excretion of Se was found to be lower in the formula-fed infants (F and PHF) compared with the HM group. There was a significant correlation between plasma and urinary Se (r = 0.62, p = 0.0001). Urinary Se ($uMg Se/g creatinine) appeared to be a good indicator of Se intake. Measurements of urine Se might be used as a screening method for the estimation of the Se supply. Weight and length increases in all infants were within the normal range. There were no differences between the different feeding groups. Glutathione peroxidase activity, human milk, infant formula, infant nutrition, screening method, selenium, selenium excretion, trace elements, twins
F Jochum, Department of Paediatrics, Heinrich-Heine-University, D-40225 Dusseldorf, Moorenstrafie 5a, Geb 23.12.02, Germany     

Neonatal hypercalcemia in preterm infants fed with human milk

Hypercalcemia (serum Ca greater than or equal to 2.83 mmol/l) was detected in 10 premature infants (gestational age: 31-37 weeks and birthweight: 1100-1950 g). All were fed with pooled human breast milk. Urinary Ca excretion was high (greater than 0.200 mmol/kg/24 h) in all but one infant while serum phosphorus (P) concentration and urinary P excretion were low. Serum immunoreactive parathyroid hormone and plasma 25-hydroxyvitamin-D concentrations were normal. A significant positive correlation was found between serum Ca concentration and urinary Ca excretion, and a negative correlation between serum Ca concentration and serum P concentration or urinary P excretion. Hypercalcemia disappeared spontaneously in two patients, was corrected by a humanized milk in three patients and by P supplementation in five patients. These data suggest that neonatal hypercalcemia is related to P depletion induced by human breast milk in premature infants.