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.     

Effects of increased calcium and phosphorous formulas and human milk on bone mineralization in preterm infants

By photon absorptiometry, extrauterine bone mineralization was evaluated in preterm infants (less than 1,600 g birth weight) fed either a commercial premature formula containing 117 mg calcium, 58.5 mg phosphorus/100 kcal, the same formula containing higher phosphorus (82 mg/100 kcal), the same formula with higher calcium (140 mg Ca) and phosphorus (82 mg/100 kcal), or their own mother's milk. All infants had serum protein, albumin, calcium, phosphorus, bicarbonate, 25-hydroxyvitamin D, and alkaline phosphatase levels done at the start of the study and every 2 weeks until they weighed 1,900 g. At the start of the study, birth weight and gestational ages were similar in all four groups. There were no biochemical differences among the four groups except for a lower serum P in the human milk group. The human milk group had lower bone mineralization rate compared with the three formula groups. Bone mineral content was similar in the three formula-fed groups. However, only formulas containing 117 mg Ca and 58.5 mg P or 140 mg Ca and 82 P mg/100 kcal approximated intrauterine bone mineralization. Human milk fed infants did not approximate and were significantly different from the intrauterine rate.     

Posthospitalization growth and bone mineral status of normal preterm infants. Feeding with mother's milk or standard formula

The growth and bone mineralization were studied in ten preterm infants fed human milk and 14 preterm infants fed cow's milk-based formula. After discharge from the hospital, at 42, 48, and 56 weeks' postmenstrual age, anthropometric measures of weight, length, occipital frontal circumference, mid-upper arm circumference, triceps, and subscapular skin folds were obtained. Blood was drawn for determinations of serum calcium, phosphorus, 25-hydroxyvitamin D, alkaline phosphatase, and albumin levels. Bone mineral analyses were performed by photon absorptiometry. Mean (+/- SD) gestational ages in nursing and formula-fed infants were similar (32.0 +/- 2.5 vs 31.5 +/- 1.5 weeks), as were their mean (+/- SD) birth weights (1.76 +/- 0.42 vs 1.52 +/- 0.30 kg). After hospitalization, both groups had similar rates of growth in weight, length, head circumference, mid-upper arm circumference, triceps, and subscapular skinfold thickness. The formula-fed group had higher serum phosphorus levels at 42 weeks, higher serum calcium levels at 48 weeks, and higher serum albumin concentrations at 56 weeks than the breast-fed group. By 56 weeks' postmenstrual age, the bone mineral content was higher in the formula-fed group. Our data suggest that after hospitalization, preterm infants fed their own mother's milk have similar growth patterns but a different bone mineralization rate compared with preterm infants fed a standard cow's milk-based formula.     

Bone mineral metabolism in full-term infants fed human milk, cow milk-based, and soy-based formulas.

OBJECTIVE--To study the hypothesis that ingestion of a modified soy-based formula with an improved mineral suspension system may result in bone mineral content similar to that observed in infants fed human milk or cow milk-based formulas. DESIGN--Prospective, self-selected group of infants fed human milk randomized between the two formula-fed groups. SETTING--University-based hospital nursery and follow-up. PARTICIPANTS--Fifty-six normal, healthy, full-term infants, free of major malformations or disorders, including 17 infants fed human milk, 19 infants fed a cow milk-based formula, and 20 infants fed a soy protein formula were followed up to 6 months' postnatal age. The soy-based formula studied was modified to improve the suspendability of the minerals. INTERVENTIONS--Infants were fed human milk or the study formula for the first 4 months, at which time beikost was permitted. Infants fed human milk received vitamin supplementation to provide 400 IU of vitamin D per day. MEASUREMENTS--Anthropometric variables, serum calcium, magnesium, phosphorus, alkaline phosphatase, and parathyroid hormone levels were measured at enrollment, and at 8, 16, and 24 to 26 weeks' postnatal age. Bone mineral content at the distal third radius site was measured with single photon absorptiometry at these times. Growth in the infants did not differ significantly among the groups. There was no significant difference in serum calcium, magnesium, alkaline phosphatase, or parathyroid hormone concentrations among the infants during the study. Serum phosphorus was significantly lower at 8 weeks in the group fed human milk than in that fed the cow milk-based formula. Bone mineral content at 16 and 24 to 26 weeks was higher in the group fed the soy-based formula than in that fed human milk, and bone width was also higher at 16 weeks in the infants fed the soy-based formula. CONCLUSIONS--Improving the suspendability of the mineral system in the soy formula results in bone mineralization in infants fed the soy-based formula similar to that measured in infants fed human milk and cow milk-based formula. We suggest that the suspendability of the minerals used is an important variable in the interpretation of the effect of feedings on the bone mineral status of infants.     

Mineral homeostasis in very premature infants: serial evaluation of serum 25-hydroxyvitamin D, serum minerals, and bone mineralization

This study was designed to evaluate the role of vitamin D sufficiency, as reflected in serum 25-hydroxyvitamin D (25-OHD) concentrations, on serum minerals and bone mineralization in very premature infants. Seventy-two infants (mean +/- SD gestation 30.1 +/- 2.5 weeks, mean +/- SD birth weight 1178 +/- 278 gm) were observed serially for the first 3 months of life. Mean serum calcium and phosphorus values, but not magnesium, remained low prior to 12 weeks. The percentage of infants with moderate to severe hypomineralization was 75% at 3 weeks, 55% at 6 weeks, 54% at 9 weeks, and 15% at twelve weeks. Low serum calcium and phosphorus values, high alkaline phosphatase activity, and moderate-severe hypomineralization were more frequent in infants weighing less than 1000 gm and in those with lower mineral intake. With a 400 IU vitamin D supplement, 45% of infants could maintain an initially normal serum 25-OHD concentration or increase low concentrations, whereas 55% had falling or persistently low (less than or equal to 15 ng/ml) 25-OHD concentrations. Birth weight and mineral intakes were comparable in these two groups, yet the group with the lower serum 25-OHD concentration had lower serum calcium and higher alkaline phosphatase values, and a higher percentage of moderate to severe hypomineralization. Regardless of birth weight, mineral intake, or 25-OHD concentration, increases in serum calcium and phosphorus values and in mineralization were seen at postconception term (12 weeks in most infants, nine weeks in those weighing 1250 to 1600 gm). At 12 weeks of age, but not before, serum 25-OHD concentration was directly correlated with serum calcium (r = 0.47, P less than 0.01) and serum phosphorus (r = 0.47, P less than 0.01) and inversely correlated with alkaline phosphatase values (r = -0.71, P less than 0.01). Mineral availability and 25-OHD sufficiency both appear to be important and to act synergistically, with neither totally compensating for the other.     

Hypophosphatemia in breast-fed low-birth-weight infants following initial hospital discharge

The present study evaluated 12 infants with birth weights less than 2000 g who received human milk plus a multivitamin supplement and 20 similar infants who received standard cow's milk formula for 16 weeks from the time of initial hospital discharge. Examination at birth, at hospital discharge (study entry), at 4 and 16 weeks after hospitalization, and at 52 weeks of age revealed no intergroup differences in body weight, length, and head circumference. Hypophosphatemia (plasma phosphorus concentration less than or equal to 1.45 mmol/L) developed in 6 infants fed human milk (5 infants at 4 weeks and 1 infant at 16 weeks of study). Mean vitamin D intakes, but not calcium and phosphorus intakes, were significantly lower during hospitalization in human milk-fed infants with hypophosphatemia (44 [25, SD] IU/d) compared with those without hypophosphatemia (322 [180] IU/d). These data indicate that human milk-fed, low-birth-weight infants are at risk for hypophosphatemia following initial hospital discharge. Plasma calcium, phosphorus, and alkaline phosphatase concentrations at hospital discharge may not predict the infants at risk. Vitamin D supplementation early in the infants' hospital course may prevent hypophosphatemia.     

Improved Bone Mineral Status in Very Low Birthweight Infants Fed Human Milk Mixed with Preterm Formula

The bone mineral status of very low birthweight (VLBW) infants fed exclusively their own mother's milk (group I) was compared with that of VLBW infants fed mother's milk in the initial 4 weeks followed by a 1:1 mixture of mother's milk and preterm formula containing high phosphorus (P) and calcium (Ca) (group II). In both groups, most infants showed a biochemical picture characteristic of phosphorus deficiency syndrome by the fourth week. Thereafter, serum alkaline phosphatase activity (ALP) decreased and serum P increased in all group II infants. Conversely, serum ALP rose and hypophosphatemia persisted in most group I infants. Group II had a significantly higher serum P at weeks 8 and 12 and a significantly lower ALP at week 12 than group I. Furthermore, group II had a lower incidence of severe radiographic abnormalities than group I at week 12. We confumed previous observations that VLBW infants fed exclusively human milk require P and Ca supplementation to prevent metabolic bone disease of prematurity.     

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.     

Bone mineralisation in premature infants cannot be predicted from serum alkaline phosphatase or serum phosphate

BACKGROUND: The bone mineral content of premature infants at term is lower than in mature infants at the same postconceptional age. Serum alkaline phosphatase and serum phosphate are often used as indicators of bone mineralisation. OBJECTIVE: To analyse the association between bone mineral content and serum alkaline phosphatase and serum phosphate. METHODS: Serum alkaline phosphatase and phosphate were measured at weekly intervals during admission in 108 premature infants of gestational age below 32 weeks (mean (SD) gestational age 29 (2) weeks; mean (SD) birth weight 1129 (279) g). Bone mineral content was measured at term (mean gestational age 41 weeks) by dual energy x ray absorptiometry and corrected for body size. RESULTS: Serum alkaline phosphatase was significantly negatively associated with serum phosphate (p < 0.001). Bone mineral content was not associated with mean serum alkaline phosphatase (p = 0.8), peak serum alkaline phosphatase (p = 0.5), or mean serum phosphate (p = 0.2) at term. CONCLUSION: Routine measurements of serum alkaline phosphatase and serum phosphate are of no use in predicting bone mineralisation outcome in premature infants.     

Evaluation of liquid or powdered fortification of human milk on growth and bone mineralization status of preterm infants.

Thirty-five preterm (< 1500 g) infants were fed preterm human milk (PHM) supplemented with either powdered fortifier (PF) or liquid supplement (LS). Bone mineral content (BMC) of the distal third radius was measured by photon absorptiometry. Biochemical indices of nutritional and bone status were obtained every 2 weeks. The initial BMC for both feeding regimens were similar. BMC did not change over the study period for infants fed LS. Infants fed PF had BMC values greater than LS infants at weeks 2 and 4 of study. Only infants fed PF had BMC values that demonstrated a consistent increase. Serum total protein and phosphorus values were greater for PF infants at week 4 than LS infants. Weight, length, occipital-frontal circumference (OFC) gains, serum albumin, alkaline phosphatase, calcium, and vitamin D levels were similar in both groups. We conclude that products used to "enrich" PHM are adequate to meet the growth needs of the preterm infant. However, we found that infants fed the powdered fortified preterm human milk had higher bone mineralization than those fed the liquid supplemented human milk.     

Fortified mothers' milk for very low birth weight infants: results of macromineral balance studies

The mineral adequacy of fortified mothers' milk for very low birth weight (VLBW) infants was tested during their first two postnatal months. Metabolic balance and serum Ca, P, Mg, Na, and K values were evaluated at 2.5 and 6 weeks of life in 32 VLBW infants (less than 1.3 kg). Infants were fed either their mothers' milk fortified with skim and cream components derived from heat-treated, lyophilized mature human milk (FMM) or commercial cow milk-derived formulas. Despite Ca and P concentrations 50% to 100% higher in the fortified human milk than is usual in unfortified human milk, group FMM's Ca and P intakes remained significantly below those fed formula (P less than 0.001). Serum calcium levels and alkaline phosphatase activity were higher and serum phosphorus lower (P less than 0.002) in group FMM, whereas serum levels of magnesium, sodium, and potassium were similar in both groups. Ninety-six-hour urinary excretion of Ca was greater and 96-hour urinary excretion of P was less in group FMM (P less than 0.02). Retention of Ca and P in both groups was significantly below estimates of intrauterine accretion. Mg retention was significantly higher in group FMM (P less than 0.002) despite intakes of Mg significantly below those in infants fed formula. Although intakes of Na were below recommended levels in both groups, by the second balance period all infants demonstrated Na retention that was greater than expected from the sum of estimates of intrauterine accretion and dermal losses. Similar findings were noted for K. Biochemical and balance data indicate that relative to the needs of the VLBW infant, fortified mothers' milk was deficient in Ca and P, but adequate in Mg, Na, and K.     

Urinary hydroxyproline: relationship to growth, bone mineral content, and serum alkaline phosphatase level in premature infants

There is little information on urinary hydroxyproline (UHP) excretion in premature infants. We hypothesized that UHP excretion would positively correlate with growth in premature infants, and that there would be correlations between UHP excretion and serum alkaline phosphatase concentration as well as bone mineral content (BMC). Twenty-six premature infants (birth weight, less than 1,300 g; gestational age, less than or equal to 32 weeks) received one of four oral feedings. Seven received mother's own milk (HM), and eight received mothers own milk fortified with 0.85 g/dl of bovine whey, 90 mg/dl of Ca, and 45 mg/dl of P. Six and five infants received Similac, 20 cal/oz (SIM) and Similac Special Care, 20 cal/oz, respectively. Measurements of UHP, serum alkaline phosphatase, BMC (photon absorptiometry), and growth were made during the 1st 7 weeks of life. The lowest UHP excretion was in the HM group. For all infants, there was a significant correlation between UHP excretion (mg/day) and absolute weight (r = 0.64, p less than 0.001), as well as rate of weight gain (r = 0.50, p less than 0.01). The UHP excretion (milligrams per day) also correlated with absolute length (r = 0.41, p less than 0.01) and rate of gain in length (centimeters per week) (r = 0.70, p less than 0.001). The UHP excretion did not correlate significantly with BMC or serum alkaline phosphatase concentration. We conclude that UHP excretion is increased in the growing premature infant compared to older infants and adults and is a good marker for somatic growth in this population.(ABSTRACT TRUNCATED AT 250 WORDS)     

Early follow-up of very low birth weight infants after hospital discharge with respect to growth and mineral homeostasis

Very low birth weight infants from two previous in-hospital feeding studies were investigated at follow-up after hospital discharge at a mean postnatal age of 12 weeks. Of infants who had received human milk in hospital (own mother's or pooled), 26 were seen at follow-up, of whom only 8 remained exclusively breast fed. Of those fed a formula in hospital, 31 were seen at follow-up. Those infants who had been fed human milk while in hospital demonstrated slower linear growth over the 6-week period of this study. Only those fed exclusively human milk from birth to the time of follow-up showed elevated serum alkaline phosphatase and low serum phosphate values, while those fed human milk in hospital, but completely or partially formula fed thereafter, had values similar to those fed formula throughout. Alkaline phosphatase values greater than 675 IU/L were associated with either exclusive breast feeding or vitamin D depletion. Of the two cases of rickets diagnosed on wrist x-rays, one infant had been exclusively breast fed and the other was vitamin D depleted.     

Rickets of prematurity: calcium and phosphorus supplementation

Seventy-four infants weighing less than 1500 gm at birth were fed enterally from birth until day 47. Group A (18 infants) were given SMA Gold Cap: group B (18 infants), supplementary calcium to 21 mmol/L (84 mg/dl); group C (16 infants), further calcium supplementation to 31.2 mmol/L (125 mg/dl); and group D (22 infants), milk with calcium content 31.2 mmol/L (125 mg/dl) and phosphorus supplementation to 15.7 mmol/L (49 mg/dl). The addition of calcium reduced the radiologic evidence of rickets, and combined calcium and phosphorus supplementation maintained plasma alkaline phosphatase activity within the normal range for 6 weeks.     

Bone mineral content, serum vitamin D metabolite concentrations, and ultraviolet B light exposure in infants fed human milk with and without vitamin D2 supplements

OBJECTIVE: To monitor ultraviolet B light exposure in human milk-fed infants both with and without supplemental vitamin D2, and to measure longitudinally the bone mineral content, growth, and serum concentrations of calcium, phosphorus, 25-hydroxyvitamin D3, 25-hydroxyvitamin D2, 1,25-dihydroxyvitamin D, and parathyroid hormone. DESIGN: Longitudinal, randomized, double-blind, placebo-controlled study of 6 months' duration. SETTING: Patients from private pediatric practice, Madison, Wisconsin. PATIENTS: Sequential sampling of 46 human milk-fed white infants; 24 received 400 IU/day of vitamin D2, and 22 received placebo. An additional 12 patients were followed who received standard infant formula. Eighty-three percent of patients completed a full 6 months of the study. MEASUREMENTS and RESULTS: Ultraviolet B light exposure and measurements of growth did not differ between groups. At 6 months, the human milk groups did not differ significantly in bone mineral content or serum concentrations of parathyroid hormone or 1,25-dihydroxyvitamin D, although total 25-hydroxyvitamin D values were significantly less in the unsupplemented human milk group (23.53 +/- 9.94 vs 36.96 +/- 11.86 ng/ml; p less than 0.01). However, 25-hydroxyvitamin D3 serum concentrations were significantly higher in the unsupplemented human milk-fed group compared with the supplemented group (21.77 +/- 9.73 vs 11.74 +/- 10.27 ng/ml, p less than 0.01) by 6 months of age. CONCLUSION: Unsupplemented, human milk-fed infants had no evidence of vitamin D deficiency during the first 6 months of life.     

Diet and bone mineral content at term in premature infants

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.     

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.     

Osteocalcin, skeletal alkaline phosphatase, and bone mineral content in very low birth weight infants: a longitudinal assessment.

Serum osteocalcin (Gla) and skeletal alkaline phosphatase (SAP) concentration both reflect osteoblast activity in the dynamic process of bone formation. To assess the relation in premature infants between change in bone mineral content (BMC) and both Gla and SAP serum concentration, we longitudinally measured BMC via photon absorptiometry and serum Gla and SAP concentration from birth to 16 wk in 20 very low birth weight infants. Serum total calcium, phosphorus, parathyroid hormone, and vitamin D metabolite concentrations were also monitored. All serum values were measured in the 20 mothers at delivery. Cord blood Gla concentrations were significantly (p less than 0.03) greater than maternal levels, and by 1 wk had significantly (p less than 0.001) increased from birth values. Total calcium, parathyroid hormone, phosphorus, and vitamin D concentrations remained in the normal range throughout the study. The increase in serum Gla concentrations, birth to 1 wk, were significantly correlated with the simultaneous increase in 1,25-dihydroxyvitamin D concentrations. The correlation between the change in BMC, however, over the first 4 mo of life and both Gla and SAP serum concentrations failed to reach statistical significance. Finally, a significant (p less than 0.003) negative correlation was measured between serum Gla and SAP concentrations at wk 4, and, although not significant, a consistently negative correlation was measured from 1-16 wk of age.(ABSTRACT TRUNCATED AT 250 WORDS)     

Serial serum 25-hydroxyvitamin D and mineral homeostasis in very premature infants fed preterm human milk

Fourteen very low birthweight infants (mean +/- SD 1,070 +/- 180 g and 29.3 +/- 1.9 weeks gestation) fed their own mother's milk were clinically followed until 3-4 months of age with frequent measurements of serum calcium, phosphorus, magnesium, 25-hydroxyvitamin D (25-OHD), parathyroid hormone, alkaline phosphatase, and albumin, and urine calcium, phosphorus, and magnesium. These infants were matched for birthweight and gestation with 14 infants (1,075 +/- 152 g and 29.0 +/- 1.7 weeks) who had been similarly followed during concomitant studies of infants fed standard formula (Similac 20 cal/oz). Urine phosphorus was markedly lower in the breast milk-fed group from initiation of feedings, and serum phosphorus became significantly lower at and after 6 weeks of age. The fall in serum phosphorus was accompanied by a marked calciuria. Parathyroid hormone was suppressed in the breast milk-fed group, although serum calcium was not elevated and did not differ from formula-fed infants. A high incidence of moderate-severe hypomineralization on radiographs was seen in both breast milk- and formula-fed groups. Six of 14 breast-fed infants required phosphorus supplementation at 8-10 weeks of age because of significant hypophosphatemia, hypercalciuria, and hypomineralization. These infants differed from those not requiring phosphorus supplements by being smaller at birth but not of lower gestation, and having persistently low serum 25-OHD at and after 6 weeks of age.     

Vitamin D metabolism, mineral homeostasis, and bone mineralization in term infants fed human milk, cow milk-based formula, or soy-based formula

The purpose of this study was to evaluate mechanisms of mineral homeostasis and mineralization in term infants with recommended vitamin D intakes. Infants fed human milk (nine), cow milk-based formula (11), or soy-based formula (11) were studied at 2 weeks and at 2, 4, 6, 9, and 12 months of age. While receiving 400 IU of vitamin D, all infants maintained serum vitamin D concentrations higher or equal to normal adult concentrations, and serum 25-hydroxyvitamin D levels were maintained at or above normal adult levels. Serum 1,25-dihydroxyvitamin D concentrations were higher than those of adults in the formula-fed but not in the human milk-fed infants. Serum calcium and phosphorus values were similar in all groups; however, urine phosphorus excretion and urine calcium excretion were adjusted to intakes. Serum parathyroid hormone values were normal in all groups. Bone mineral content significantly increased with age similarly in all groups; however, an apparent plateau occurred at 6 months of age in all groups. Bone width steadily increased with age. Taken as a whole, these data suggest that the vitamin D-sufficient term infant fed human milk, cow milk-based formula, or the soy-based formula studied can regulate mineral metabolism within acceptable physiologic limits to attain similar levels of serum minerals and bone mineral content.