Diet and bone mineral content at term in premature infants. Growth, biochemical status, and mineral metabolism in very-low-birth-weight infants receiving fortified preterm human milk. Bone mineralization and mineral homeostasis in very low-birth-weight infants fed either human milk or fortified human milk. Growth of very low birth weight infants on varying amounts of human milk protein. Bone mineralization in preterm infants fed human milk with and without mineral supplementation. Changes in growth and metabolism in very low birthweight infants fed with fortified breast milk. Improved bone mineralization and growth in premature infants fed fortified own mother's milk. Moderate nutrient supplementation of mother's milk for preterm infants supports adequate bone mass and short-term growth: a randomized, controlled trial. Rickets in very-low-birth-weight infants born at Baragwanath Hospital. Growth, nutrient retention, and metabolic response of low-birth-weight infants fed supplemented and unsupplemented preterm human milk. Randomized outcome trial of human milk fortification and developmental outcome in preterm infants. Growth and phosphorus metabolism in premature infants fed human milk, fortified human milk, or special premature formula. Use of serum procollagen as a marker of growth.
Premature infants are at risk of developing metabolic bone disease mainly because of low calcium and phosphorus intake. We have examined the effect of different mineral supplements on bone mineral content at term in 127 premature infants with gestational age <32 wk in a double-blinded randomized trial. We used either phosphate supplementation of human milk as recommended by the European Society of Pediatric Gastroenterology and Nutrition or fortified supplementation with protein, calcium, and phosphorus or preterm formula as recommended by the American Academy of Pediatrics. The intervention period was from 1 week old until 36 wk of gestational age, and the infants were fed approximately 200 mL x kg(-1) x d(-1). Bone mineral content was measured at term by dual-energy x-ray absorptiometry scan. Surprisingly, neither phosphate, fortifier, nor preterm formula supplementation had any significant effect on bone mineral content at term compared with infants fed their own mother's milk only. There was a tendency to higher total bone mineral content in infants fed preterm formula compared with infants fed their own mother's milk only (p = 0.05), but when the bone mineral content was corrected for the size of the infant, there was no difference (p = 0.68). Infants fed preterm formula had a significantly higher weight at term compared with infants fed their own mother's milk only (p = 0.02), but did not differ significantly in length or head circumference. In a regression analysis, the amount of supplemented phosphorus was significantly associated with weight at term (p = 0.008). We conclude that when feeding 200 mL x kg(-1) x d(-1), mineral supplementation of human milk or use of preterm formula does not significantly improve bone mineralization outcome at term. 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. 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. In a double-blind, randomized study, 28 healthy, growing very low birth wt, appropriate-for-gestational-age infants were fed human milk, preferably mother's own, fortified daily with human milk protein and/or human milk fat. The infants entered the study when they were stable on complete enteral intakes of 170 mL/kg/d (mean age = 19 d). The study lasted for a mean of 4 wk. Samples from all the milks were collected daily, and intakes of protein, fat, carbohydrates, energy, and electrolytes were calculated weekly during the whole study period. Protein intakes ranged from 1.7 to 3.9 g/kg/d, and energy intakes from 100 to 150 kcal/kg/d. Wt and length gain in the nonprotein-enriched groups were 15.6 +/- 2.7 g/kg/d (mean +/- SD) and 0.88 +/- 0.17 cm/wk; the corresponding figures for the protein-enriched groups were 20.2 +/- 2.1 g/kg/d and 1.24 +/- 0.14 cm/wk. There was a strong correlation between protein intake and growth in wt and length up to an intake of about 3 g/kg/d; more protein did not result in increased growth. The same was true for energy intake, with a maximal growth rate at an intake of about 120 kcal/kg/d. A protein intake of more than 3 g/kg/d resulted in a growth rate equal to or higher than the estimated intrauterine growth rate. Some infants fed mature banked human milk alone had a poor growth. Sodium intake was low, ranging from 1.5 to 2.6 mmol/kg/d. No correlation was found between sodium intake and growth rates. 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. Human milk is often inadequate nutritionally for preterm infants. We investigated the effect of adding a commercially prepared milk fortifier to human (maternal or bank) milk and measured changes in lower leg length velocity (LLLvel) using knemometry, weight gain and biochemical indices of nutrition. Babies were allocated to one of three feed groups, in a semi-randomized fashion, to receive human milk alone (group I), fortified human milk (group II) or a preterm formula (group III). The birthweights (median and R) and birth gestations (median and R) of the three groups were as follows: group I 1099 g (654-1248 g) and 28 wk (26-32 wk); group II 838 g (742-1340g) and 31 wk (28-36); group III 1136g (624-1552g) and 32 wk (27-36 wk). All babies who received fortified milk either showed significant (p = 0.0004) acceleration in LLLvel during the period studied, or maintained their pre-study period velocity. This increase in LLLvel was comparable to that achieved by a group of babies given a standard preterm infant formula (p < 0.001). By comparison, the control group's change in LLLvel was more modest (p = 0.04). Babies who received human milk with the fortifier added had the lowest serum levels of alkaline phosphatase at the end of the study period when compared to the other two groups. Other biochemical indices were similar in the three feed groups. No adverse clinical events were encountered which could be attributed to the use of the breast milk fortifier. "Preterm" human milk fortified with protein (0.85 gm/dL), calcium (90 mg/dL), and phosphorus (45 mg/dL) was compared with unfortified preterm human milk as a feeding for low birth weight infants. Additionally, a special formula for low birth weight infants (Similac Special Care (SC), 20 cal/oz), was compared with a standard 20 cal/oz formula (Similac). Bone mineral content (BMC), as measured by photon absorptiometry, improved in the study groups fed fortified human milk and Similac SC formula during the first 6 weeks of full oral feedings. Even though the intakes of calcium in the groups fed fortified human milk and Similac SC formula approached the intrauterine requirement for Ca during the third trimester of pregnancy (150 mg/kg/d), the values for BMC in these two groups (37 to 39 mg/cm) at the completion of the study were still considerably less than the intrauterine values for radial BMC at 36 to 37 weeks gestational age (72.6 +/- 14.1 mg/cm). Furthermore, the relative phosphorus deficiency (as determined by increased urinary Ca excretion and increased renal tubular reabsorption of phosphate) in the human milk groups occurred with or without supplements of Ca and P. Rate of weight gain in the fortified human milk group was greater than that of the unfortified human milk group and was comparable to that of infants fed Similac SC formula. Rate of weight gain for the unfortified human milk group was similar to that of infants fed Similac formula containing 20 cal/oz. However, none of the four feeding groups exceeded the 50th percentile for weight at the time of discharge (36 to 37 weeks postconceptional age). The results suggest that fortifying preterm human milk with Ca, P, and protein for low birth weight infants will improve bone mineralization and rate of growth to levels comparable to those achieved with a special formula containing high amounts of protein, Ca, and P. Our objectives were 1) to determine whether moderate nutrient supplementation of mother's milk (MM) for preterm infants, in the form of a new multinutrient fortifier (MNF), would improve short-term growth and bone mineral content (BMC) when compared with supplementation with calcium and phosphorus alone; and 2) to investigate whether moderate calcium and phosphorus intakes, in the form of calcium glycerophosphate (CaGP), resulted in a BMC similar to that of term corrected infants. Twenty-five preterm infants fed MM were randomly assigned to receive either MM+MNF or MM+CaGP. A third group of infants fed preterm formula (PTF) served as a comparison group. Whole-body BMC and lean and fat mass were determined by dual-energy X-ray absorptiometry (DXA) at full-term age. Nitrogen retention and calcium, phosphorus, and zinc intakes were determined by using mass balance techniques. Nitrogen retention was significantly lower in the MM+CaGP group than in the PTF group as were both weight and length gain (weight gain: 16.6 +/- 1.6, 14.2 +/- 2.0, and 16.1 +/- 2.9 g x kg(-1) x d(-1); length gain: 1.1 +/- 0.2, 0.9 +/- 0.2, and 1.1 +/- 0.3 cm/wk for the MM+MNF, MM+CaGP, and PTF groups, respectively). Biochemical indexes of mineral status and bone turnover were normal. Conservative amounts of calcium and phosphorus, as CaGP, resulted in adequate BMC. Moderate amounts of protein, calcium, and phosphorus plus trace elements added to MM in the form of an MNF resulted in improved linear growth but did not provide any advantages to BMC when compared with supplementation with calcium and phosphorus alone. Disturbed mineral and bone metabolism has been reported to occur frequently in very-low-birth-weight infants fed breast-milk during the first 3 months of life. This study was designed to assess the prevalence of disturbed mineral homeostasis in a breast-milk-fed very-low-birth-weight population at Baragwanath Hospital and to determine whether the addition of a preterm infant formula to the feeds would reduce this prevalence and increase the rate of weight gain. Fifty-three neonates weighing less than 1 200 g at birth were monitored for weight gain, growth and biochemical and radiological evidence of metabolic bone disease at 2-weekly intervals during hospitalisation and for 18 weeks after discharge. The infants were randomised at 2 weeks of age to receive either breast-milk only, or a combination of breast-milk and a premature formula containing 550 mg calcium and 300 mg phosphorus. All infants received 800 IU vitamin D daily from day 14. Weight gain and growth were similar in both groups. Calcium and phosphorus intakes were higher in the mixed feeding group, but did not affect serum mineral levels. Radiological rickets was uncommon in both groups although periosteal reactions and osteopenia occurred frequently and with similar prevalences. Vitamin D deficiency was not found to be a problem. In conclusion, overt rickets is not a major problem in very-low-birth-weight infants born at Baragwanath Hospital, although biochemical abnormalities occur frequently.(ABSTRACT TRUNCATED AT 250 WORDS) Growth, nutrient retention, and metabolic response of low-birth-weight infants fed human milk provided by their mother; this milk supplemented with bovine milk protein, calcium, phosphorus, and sodium; or pasteurized term human milk with the same supplement were monitored from the time desired intake was tolerated until weight reached 2200 g. The supplement resulted in greater rates of weight gain (20.5 +/- 2.3 vs 16.4 +/- 2.2 g.kg-1.d-1) and nitrogen retention (353 +/- 76 vs 270 +/- 53 mg.kg-1.d-1), increase in plasma transthyretin (TTR) concentration (7 +/- 16 vs -3 +/- 9 mg.L-1.wk-1), a higher mean plasma albumin concentration (34 +/- 3 vs 32 +/- 4 g/L), and a higher plasma TTR concentration at discharge (100 +/- 22 vs 75 +/- 24 mg/L). All these variables correlated significantly with total nitrogen intake, suggesting that the differences are attributable to the protein content of the supplement. The supplement also resulted in greater rates of calcium and phosphorus accretion but the plasma alkaline phosphatase activity of the supplemented vs the unsupplemented groups did not differ. Despite potential benefits, human milk may fail to meet preterm infants' nutrient requirements. We tested the hypothesis that fortified breast milk, fed alone or with preterm formula, would improve neurodevelopment and growth at 18-mo follow-up without adverse short-term clinical or biochemical consequences. Two hundred seventy-five preterm infants from two medical centers (birth weight < 1850 g; mean gestation 29.8 +/- 2.7 wk) whose mothers chose to provide breast milk were randomly assigned to receive for a mean of 39 d a multinutrient fortifier or control supplement containing phosphate and vitamins. Breast milk comprised 47.6% and 46.4% of enteral intake in fortified and control groups, respectively; preterm formula supplements were used when insufficient breast milk was available. Overall, there were no significant growth advantages with fortification; although, when breast milk exceeded 50% of intake, fortification promoted faster weight gain (an advantage of 1.6 g.kg-1.d-1; 95% CI: 0.1, 3.1; P < 0.05). Compared with control infants, the fortified group showed 1) higher plasma urea from week 2 (P = 0.04), 2) higher plasma calcium (mean 2.34 +/- 0.01 compared with 2.27 +/- 0.02 mmol/L; P = 0.003), 3) a greater rise in alkaline phosphatase by week 6 (P = 0.04), 4) more clinical infections (suspected plus proven; 43% compared with 31%, P = 0.04), 5) a nonsignificantly increased incidence of necrotizing enterocolitis (5.8% compared with 2.2%, P = 0.12), and 6) higher white cell and platelet counts. Developmental scores at 18 mo were slightly but not significantly higher in the fortified group. This study confirmed that breast milk fortifiers can improve short-term growth (when breast milk intakes are high); but beneficial effects on long-term development remained unproven. Future research is required to evaluate potential adverse consequences and explore more optimal fortification strategies. Human milk promotes less than optimal growth and is associated with phosphorus deficiency and decreased bone mineralization in very-low-birth-weight (VLBW) infants. In this study, the effects of feeding premature infants either human milk (HM), fortified human milk (FHM), or special premature formula (Similac Special Care [SSC]) on growth, phosphorus metabolism, and serum type I procollagen (pColl-I-C) were evaluated. Infants fed FHM exhibited a rate of weight gain and an increase in head circumference comparable with infants fed SSC and significantly greater than infants fed HM, despite the fact that both the FHM group and the HM group demonstrated biochemical evidence of phosphorus deficiency. The pColl-I-C concentrations in VLBW infants were tenfold to 20-fold greater than concentrations in normal children older than 2 years of age. The pColl-I-C levels correlated positively with weight gain and were significantly greater in the FHM and SSC groups than in the HM group. By contrast, serum alkaline phosphatase levels did not correlate with weight gain and were significantly lower in the rapidly growing SSC group than in either of the two groups with phosphorus deficiency and presumed poor bone mineralization. We conclude that the serum pColl-I-C concentration is a biochemical marker of growth in VLBW infants and may prove useful as a predictor of growth responses to various nutritional and therapeutic interventions.
Multicomponent fortification of human milk is associated with short-term improvements in weight gain, linear and head growth. Despite the absence of evidence of long-term benefit and insufficient evidence to be reassured that there are no deleterious effects, it is unlikely that further studies evaluating fortification of human milk versus no supplementation will be performed. Further research should be directed toward comparisons between different proprietary preparations and evaluating both short-term and long-term outcomes in search of the "optimal" composition of fortifiers.