Growth, biochemical status, and mineral metabolism in very-low-birth-weight infants receiving fortified preterm human milk

We compared the growth, biochemical status, and mineral status of 30 very-low-birth-weight infants randomly assigned to receive preterm human milk (Group I, 10 infants) from their own mothers, fortified preterm human milk (Group II, 8 infants), or a high-caloric-density premature formula (Group III, 12 infants). Added to the infant's own mother's milk, a human milk fortifier at full strength provided additional protein (60:40 whey/casein, 0.7 g/dl), calories (4 kcal/oz), and minerals. Volume of intake, feeding tolerance, and complications were similar in the three groups. Infants receiving fortified preterm human milk showed growth, biochemical status, and mineral status similar to those receiving high-caloric-density formula, but infants receiving fortified preterm human milk grew faster (12.0 +/- 3.2 vs. 8.9 +/- 1.1 days/300 g, p less than 0.05), had higher serum protein (4.6 +/- 0.5 vs. 4.2 +/- 0.2 g/dl, p less than 0.05), and tended to have better mineral status (higher serum calcium, lower alkaline phosphatase, and higher serum phosphorus, none individually significant) than infants receiving preterm human milk alone. This study supports previous observations that fortified preterm human milk provides nutritional advantages for very-low-birth-weight infants.     

哈尔滨地区早产儿母乳营养素含量的调查研究

目的了解当前哈尔滨地区早产儿母乳中各种营养素的含量,为研制国内早产儿强化母乳提供科学依据,为更加合理喂养早产儿促进其健康成长提供科学依据。方法收集哈尔滨市四个地区62名产妇的乳汁(早产儿初乳32份、成熟乳28份;足月儿初乳及成熟乳各30份),测定乳汁中蛋白质、脂肪、钙、磷、镁、铜、铁、锌、锰的含量。结果哈尔滨地区早产儿母乳中蛋白质、磷、锌、镁在成熟乳期下降明显,铁、铜略有下降,但差异无统计学意义,脂肪、锰随泌乳期呈上升趋势,钙无明显变化。早产儿母乳在初乳及成熟乳期蛋白质含量均高于足月儿母乳,其他元素差异两者间无统计学意义。结论早产儿母乳中蛋白质、锌、脂肪含量在成熟乳阶段含量偏低,建议适当补充,注意喂养。     

Bone mineralization in preterm infants fed human milk with and without mineral supplementation

The bone mineral status of healthy preterm infants fed maternal milk was compared with that of similar infants fed maternal milk with mineral supplementation. Fifty infants with birth weight less than 1600 g were fed human milk for 1 week until reaching an intake of 120 kcal/kg/d. Thereafter, infants were assigned randomly to one of three diets: (1) continued unsupplemented human milk, providing an intake of 40 to 50 mg/kg/d calcium and 23 to 30 mg/kg/d phosphorus; (2) human milk mixed with a high mineral containing formula, providing total intakes of 130 mg/kg/d calcium and 68 mg/kg/d phosphorus; or (3) human milk alone for 1 additional week, followed by human milk mixed with a powdered fortifier, providing total intakes of 160 mg/kg/d calcium and 90 mg/kg/d phosphorus. Infants fed human milk with formula supplementation, but not those fed human milk with fortifier, had significantly higher serum phosphorus concentrations and significantly lower serum alkaline phosphatase concentrations than did those fed unsupplemented human milk (P less than 0.01). Bone mineral content of the humerus, determined by photon absorptiometry, however, was similar in all three groups; values averaged 0.104 g/cm at the beginning of the study, and remained unchanged irrespective of mineral supplementation. Shortly before hospital discharge, study diets were discontinued and infants were fed standard proprietary formula or were nursed by their mothers. At 44 weeks postconceptional age (7 to 10 weeks after change in diet), infants were reexamined. Serum phosphorus concentrations increased, serum alkaline phosphatase concentrations decreased, and bone mineral content more than doubled to values comparable with those in term infants. Results at follow-up were comparable for all three initial diet groups and for infants who were formula-fed or breast-fed after hospital discharge. The lack of any significant effect of early maternal milk supplementation on bone mineralization by 44 weeks postconceptional age suggests that these methods of supplementation of maternal milk may not be warranted for healthy preterm infants.     

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.     

Early diet of preterm infants and bone mineralization at age five years

Bone disease with significantly reduced bone mineralization is common in preterm infants, and associated with later linear growth stunting at 18 months of age. Dietary insufficiency of calcium and phosphorus is thought to be the principal aetiological factor. We studied 54 children at mean age 5 years who were born preterm and had participated in a prospective multicentre study of effects of early diet on later growth and development. Diets compared were banked donor breast milk and preterm formula fed as a supplement to mother's own milk. Increasing human milk intake was strongly positively associated with later bone mineral content. Children fed predominantly human milk had greater bone mineral content than children of similar size born at term. These data suggest that the early nutritional environment of the preterm infant could play an important role in determining later skeletal growth and mineralization.     

Fatty acid balance studies in preterm infants fed formula milk containing long-chain polyunsaturated fatty acids (LCP) II

A milk formula (Prematil-LCP) containing long-chain polyunsaturated fatty acids (LCP) and with a fatty acid profile closely resembling breast milk has recently been introduced for preterm infants. A double-blind randomized controlled trial was performed comparing fatty acid absorption from Prematil-LCP (n = 10) and standard Prematil (n = 10). Formula-fed preterm infants underwent 3 d fat balances (once full enteral feeds were established) along with a parallel human milk fed group (n = 11). Plasma samples were taken on the last day. Median total fat excretion (absorption, %) was 2.34 g kg (82.0), 2.64 g kg (82.9) and 1.65 g kg (87.8) with Prematil, Prematil-LCP and human milk feeding, respectively. This reflected differences in the excretion and absorption of long-chain saturated fatty acids. All groups excreted detectable LCP. LCP disappearance was higher in infants fed human milk than in those fed Prematil-LCP, particularly for n -6 LCP (p <0:01). Nevertheless, excreted LCP equated to <30% dietary intake, with Prematil-LCP feeding. Plasma lipid fatty acid composition reflected differences in dietary LCP intake.     

Visual evoked potentials and dietary long chain polyunsaturated fatty acids in preterm infants.

The influence of dietary long chain polyunsaturated fatty acid (LCP) supply, and especially of docosahexaenoic acid (DHA), on evoked potential maturation, was studied in 58 healthy preterm infants using flash visual evoked potentials (VEPs), flash electroretinography (ERG), and brainstem acoustic evoked potentials (BAEPs) at 52 weeks of postconceptional age. At the same time, the fatty acid composition of red blood cell membranes was examined. The infants were fed on breast milk (n = 12), a preterm formula supplemented with LCP (PF-LCP) (n = 21), or a traditional preterm formula (PF) (n = 25). In the breast milk and PF-LCP groups the morphology and latencies of the waves that reflect the visual projecting system were similar; in the PF group the morphology was quite different and the wave latencies were significantly longer. This could mean that the maturation pattern of VEPs in preterm infants who did not receive LCP was slower. Moreover, a higher level of erythrocyte LCP, especially DHA, was found in breast milk and PF-LCP groups compared with the PF group. ERG and BAEP recordings were the same in all three groups. These results suggest that a well balanced LCP supplement in preterm formulas can positively influence the maturation of visual evoked potentials in preterm infants when breast milk is not available.     

Randomised trial of nutrition for preterm infants after discharge.

In a randomised double blind trial, the effect on growth and clinical status of a nutrient enriched 'post-discharge' milk formula versus a standard term formula, was compared in 32 exclusively bottle fed preterm infants. The formulas were used as the sole milk intake up to a postnatal age of 9 months. Significant increases in linear growth and weight gain were observed in the infants who received the enriched diet. There were no differences in vomiting, posseting, or bowel habit between the groups. Formula volumes ingested were similar between diet groups, indicating that the difference in formula composition did not affect the infants' regulation of intake. These preliminary data suggest that there is a role for specially designed formulas for preterm infants after discharge from hospital.     

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.     

Bone mineralization outcomes in human milk-fed preterm infants.

We evaluated bone mineralization by single photon absorptiometry at 2 y in a cohort of preterm infants studied since birth. Infants were fed human milk fortified with Ca [to achieve 80 mg/dL (19.96 mmol/L)] and P [40 mg/dL (12.91 mmol/L)] from wk 2 through 8 after birth. After hospital discharge, infants were divided into two groups (HM and F) determined by the timing of the introduction of cow milk-based formula. Mid-radius bone mineral content (BMC) was assessed in 10 infants who were breast-fed (HM) for a minimum of 2 mo after hospital discharge and 11 who were bottle-fed (F). The mean duration of human milk-feeding differed by design between HM and F groups (31 +/- 15 versus 11 +/- 3 wk, respectively). Although we had observed previously that group F had significantly greater BMC values at 16, 25, and 52 wk compared with values in group HM, we found similarities in BMC values (180 +/- 30 mg/cm) between groups at 2 y. The 2-y cohort comprised healthy infants and the groups had similar birth weights, lengths of gestation, and values for weight (10.8 +/- 1.1 kg), length (82 +/- 2 cm), and bone width (7.8 +/- 1.1 mm). Follow-up outcomes at 2 y in preterm infants fed fortified human milk in hospital suggest that if they continue to receive human milk after hospital discharge, radius BMC will "catch-up" to that of similar infants given formula in the posthospitalization period.     

Partition of nitrogen intake and excretion in low-birth-weight infants

Although nitrogen balance studies have been carried out in low-birth-weight infants, few have partitioned the nitrogen into its components. In this study, 72-hour balance studies were conducted in 24 low-birth-weight infants (gestational age, 30.7 +/- 1.6 weeks; birth weight 1.36 +/- 0.25 kg) fed their mothers' milk (preterm milk) or 50% preterm milk and 50% formula. Total nitrogen, nonprotein nitrogen, and whey protein intake and excretion were measured. Total nitrogen intake (preterm milk group, 452 +/- 138 mg/kg per day; preterm + formula group, 406 +/- 93 mg/kg per day), absorption (85%), and retention (71%) were not significantly different between groups. Intact and fragments of secretory IgA and lactoferrin were detected in soluble fecal extracts, and represented 25% and 9% of intake, respectively. Feeding preterm milk allows for nitrogen accretion similar to intrauterine growth rates for 5 weeks postnatally, and provides potentially functional proteins for the low-birth-weight infant.     

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     

Iron nutritional status in preterm infants fed formulas fortified with iron.

AIMS: To prospectively evaluate the iron nutritional status of preterm infants fed either a term (0.5 mg/dl iron) or preterm (0.9 mg/dl) formulas fortified with iron after hospital discharge. METHODS: Healthy low birthweight preterm infants were randomly assigned into three groups at the time of hospital discharge. Group A were fed an iron fortified preterm formula (0.9 mg/dl iron) until 6 months corrected age; group B, a fortified term formula (0.5 mg/l iron) until 6 months corrected age group C, the preterm formula between hospital discharge and term, then the term formula until 6 months corrected age. RESULTS: Seventy eight infants were followed up to 6 months corrected age. Iron intake from formula differed significantly between the groups (A, 1.17 mg/kg/day (SD 0.32) > C, 0. 86 mg/kg/day (SD 0.40) = B, 0.81 mg/kg/day (SD 0.23); p < 0.0001). Haemoglobin concentrations were similar to those of iron sufficient preterm infants of the same postnatal age, and term infants of the same postmenstrual age (after 3 months of age). There were no significant differences in haemoglobin concentration (p = 0.391), plasma ferritin (A vs B, p = 0.322), or in the incidence of iron deficiency (A vs B, p = 0.534). CONCLUSIONS: Iron fortified formulas containing between 0.5 and 0.9 mg/dl iron seem to meet the iron nutritional needs of preterm infants after hospital discharge.     

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.     

Energy balance,nitrogen balance,and growth in preterm infants fed expressed breast milk,a premature infant formula,and two low-solute adapted formulae.

Energy balance, nitrogen balance, and growth studies were done in 37 preterm infants (20 of very low birthweight) who were fed on expressed breast milk or on one of 3 formulae each of different composition, including a special premature formula and a highly adapted ''humanised'' formula. The variability of breast milk composition was such that it would have been difficult to predict the infants'' protein and energy intakes under normal nursing conditions. All measured parameters of nutritional performance were best in infants fed on the ''premature'' formula and were reflected in greater weight gain, linear growth, and head growth. The nitrogen balance data suggest that the highly adapted formula, which had a protein content comparable with that of mature human milk, contained too little protein for small preterm infants.     

Mineral balance and whole body bone mineral content in very low-birth-weight infants

Fat and mineral metabolic balance studies were performed in 25 normal very low-birth-weight infants ( 1500 g at birth) fed either pooled pasteurized human milk supplemented with calcium, phosphorus and magnesium, or a preterm formula. Calcium, phosphorus and magnesium intake were similar in both groups and averaged 100mg/kg/day, 72 mg/kg/day and 8 mg/kg/day, respectively. Calcium and phosphorus retention was higher in the subjects fed fortified human milk than in those receiving a preterm formula (65±14 and 62±9mg/kg/day versus 55±12 and 47±7mg/kg/day respectively). The difference was only significant for phosphorus. Magnesium retention was similar in the two groups and averaged 3 mg/kg/day. Fat intake and absorption was significantly higher in the preterm formula fed group than in the one fed fortified human milk (5.5±0.4 g/kg/day and 88±4% versus 4.2±1 g/kg/day, 79±6% respectively). Assessment of the whole body bone mineral content by dual energy X-ray absorptiometry was performed at 3 and 6 months of age in another group of 25 low-birth-weight infants fed either fortified human milk or a preterm formula. Whole body bone mineral content (BMCt) was low (43.3±30.8 g of hydroxyapatite) at 3 months of age (theoretical term) compared to normal full-term newborns at birth. There was no significant influence of the diet. At 6 months of age, BMCt reached 168.6±36.6g, a value similar to that of full-term newborns, with no significant difference between the two regimen groups. The deficit in the 12 subjects who had a BMCt under 30 g at 3 months of age had been corrected at age 6 months. Premature babies fed a pooled pasteurized human milk enriched with calcium, phosphorus and magnesium favored a better retention of calcium and phosphorus. However, no significant influence of the two diets studied was observed on the gain in BMCt over the first 6 months of life.     

Zinc and copper in preterm neonates: Relationship with breast milk

The study was conducted to assess copper and zinc levels in neonate’s serum, mother’s serum, neonate’s hair and urine and to ascertain association between them. It is of concern whether zinc and copper deficiency is present at birth and maternal blood and breast milk zinc and copper levels have any effect on this. The study sample included 155 neonates with gestational age 26–41 wks and birth weight 0.550-3.800 kg. Mother’s serum, breast milk, neonate’s serum, hair, urine samples were analysed for zinc and copper by atomic absorption spectrophotometry. Gestational age was estimated either singly or by combination of date of last normal menses, fetal ultrasonography, and postnatal measures of physical and neurological development by clinical examination and weight by Secca electronic balance. The neonates were classified into term and preterm, small (SGA) and appropriate for gestational age (AGA). Neonates over 37 wks and 2.5 kg served as controls. To assess the dependency, relationship and effectiveness of quantitative predictive variables on the predictions of values, multiple regression analysis was used. Neonates between 26–30 wks gestational age and <2.5 kg birth weight had significantly low serum zinc and copper. Breast milk zinc was low in mothers delivering preterm and <2.5 kg neonates. Urinary copper and zinc levels were high in preterm appropriate for gestational age (Pre AGA) than term neonates. Multiple regression analysis revealed that neonate’s serum Cu, serum Zn, hair Cu, hair Zn, urine Cu and urine Zn had contribution variability of 49.8%, 51.8%, 49.2%, 16.6%, 52.2% and 68.9%, respectively. The effect of mother’s serum, breast milk, and neonate’s serum copper and zinc collectively was significant for serum copper (F = 29.59) and hair zinc (F = 32.03). Preterm and low birth weight infants during subsequent growth and development should be supplemented with zinc and copper when on breast feeding     

Pasteurization of mother's own milk reduces fat absorption and growth in preterm infants

AIM: A randomized study was conducted to evaluate whether pasteurized milk (Holder pasteurization 62.5 degrees C, 30 min) reduces fat absorption and growth in preterm infants. METHODS: Preterm infants (825-1325 g) born with gestational age < or =30 weeks were randomized into two groups, of which one started with pasteurized own mother's milk for 1 week and continued with raw milk the following week, and a second group was fed in reverse order. By using this design the infants served as their own controls. At the end of each week, a 72-h fat balance was performed and growth was monitored. RESULTS: We found, on an average, 17% higher fat absorption with raw as compared to pasteurized milk. Infants gained more weight and linear growth assessed as knee-heel length was also greater during the week they were fed raw milk as compared to the week they were fed pasteurized milk. CONCLUSION: Feeding preterm infants pasteurized as compared to raw own mother's milk reduced fat absorption. When the infants were fed raw milk, they gained more in knee-heel length compared to when they were fed pasteurized milk.     

Changes in the fatty acids pattern of red blood cell phospholipids induced by type of milk, dietary nucleotide supplementation, and postnatal age in preterm infants

The fatty acid profile of red blood cell phospholipids and the total phospholipid and cholesterol contents of erythrocyte membrane in preterm infants in the first month of life were studied. Influences of human milk and adapted formula and dietary nucleotides supplementation at a level similar to that found in human milk were evaluated. Nineteen preterm newborn infants with adequate weight for gestational age were fed their own mother's preterm human milk, 18 with a standard milk formula and 18 with the same formula supplemented with nucleotides. Blood samples were obtained at birth from cord blood, and at 30 days of age. At 1 month of life, linoleic acid rose in formula fed infants compared to those fed human milk (p less than 0.05) and relative amounts of 20:3w6, 20:4w6, 22:4w6, 22:5w6, and total polyunsaturates of the w6 series greater than 18 carbon atoms were significantly decreased in standard milk formula fed infants (p less than 0.05-0.01). No significant differences for these fatty acids were found between human milk and nucleotide milk formula infants. Docosahexaenoic acid (22:6w3) decreased from birth to 1 month of age in formula fed infants (p less than 0.01) but not in human milk fed infants. Infants fed nucleotide milk formula showed intermediate values for 20:3w6 and 20:4w6 (p less than 0.1) between infants fed human milk and those fed standard milk formula.(ABSTRACT TRUNCATED AT 250 WORDS)     

Nutritional efficacy of preterm formula with a partially hydrolyzed protein source: a randomized pilot study.

BACKGROUND: Decreased nitrogen levels, calcium intestinal absorption rates, and plasma amino acid imbalances were reported for preterm infants who were fed partially hydrolyzed preterm formulas. In this pilot study, we evaluated a new formula with modified nitrogen and calcium sources. METHODS: During their second week of life, 16 preterm infants were randomly assigned to one of two groups: 9 were fed the new partially hydrolyzed formula and 7 were fed a conventional formula. Nutrient balance was performed at the end of the first month of life. Amino acid concentrations and anthropometric parameters were measured at theoretical term. RESULTS: Birth weight and gestational age (mean +/- SD) were similar in the two groups (28.9 +/- 7.0 weeks and 1183 +/- 242 g vs. 27.7 +/- 1.0 weeks and 1139 +/- 162 g). Median nitrogen absorption rates (85% vs. 89%; P = 0.03) and biological values (59% vs. 69%; P = 0.13) were lower for infants who were fed the new formula than for those fed the conventional formula. After correction for difference in nitrogen intake, there was no significant difference in nitrogen retained between the two groups (P = 0.11). Plasma amino acid concentrations were also similar in the two groups. Median calcium absorption tended to be higher in the new-formula group than in the conventional-formula group (54% vs. 45%, P = 0.19). At theoretical term, infants fed the conventional formula were heavier than infants fed the new formula (3559 +/- 362 g vs. 3193 +/- 384 g, P = 0.04). CONCLUSIONS: Because nitrogen content is 10% higher in hydrolyzed-protein formula than in entire-protein formula, appropriate nitrogen retention, plasma amino acid profile, and mineral use can be achieved with the new partially hydrolyzed formula. Further studies with larger groups are needed to evaluate the effect on growth.