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De novo endogenous cholesterol synthesis is an integral component of developing human infant adaptive mechanisms that regulate cholesterol homeostasis. Smaller central pools of cholesterol later in life may contribute to reduced low-density lipoprotein-cholesterol (LDL-C) concentrations in the plasma and thus reduce the risk of cardiovascular disease. Early infant adaptive mechanisms may theoretically result in altered central pools of cholesterol in later life. To examine the response of cholesterol homeostasis to long-term dietary cholesterol supplementation, endogenous cholesterol synthesis was studied in 81 full-term healthy neonates at 4 months or at 11 and 12 months of age. Thirty-two infants were breast-fed (BF) (6 males, 7 females), fed regular cows milk protein-based formula (RF) (6 males, 3 females) 0.85 mmol cholesterol/L (33 mg cholesterol/L), or fed regular cow milk protein-based formula with the addition of cholesterol (RF+cholesterol) (5 males, 5 females) 3.44 mmol cholesterol/L (133 mg cholesterol/L). Effects of cholesterol supplementation on cholesterol synthesis rates were evaluated at 4 months of age. Forty-nine other infants, BF (11 males, 6 females) fed RF (7 males, 12 females), or RF+cholesterol (6 males, 7 females) until 6 months of age were studied to test the hypothesis of imprinting using a cross-over design study with a 1-month 250 mg cholesterol/day challenge at 11 months of age. The incorporation rate of deuterium in body water into erythrocyte-free cholesterol over 48 hours was used as an index of cholesterol fractional synthetic rate (FSR) at 4, 11, and 12 months of age. Both plasma total- and LDL-C were higher (P <.04) in BF compared with RF+cholesterol and RF formula-fed groups at 4 months of age. Plasma cholesterol concentrations for all 3 groups were similar at 11 and 12 months of age. FSR (pools/d) was 4-fold higher (P <.0001) in both RF and RF+cholesterol compared with BF groups, but not different between RF and RF+cholesterol formula-fed groups. No differences in FSR before and after cholesterol challenge were observed within the 3 feeding groups at 11 and 12 months of age. However, synthesis rates from 4 months to 12 months increased (P <.03) in BF infants and decreased in both RF+cholesterol (P <.0001) and RF (P <.0001) fed groups. These results demonstrate relative insensitivity of synthesis rates and serum cholesterol concentrations to cholesterol challenge, irrespective of early dietary cholesterol intake in formula-fed and BF infants. These findings support the notion that early dietary cholesterol causes minimal changes in cholesterol metabolism about 6 months after dietary exposure in young infants., (Copyright 2002 by W.B. Saunders Company)

We investigated whether supplementation of regular formula (RF) with cholesterol (Ch) (RF+Ch) influenced circulating Ch levels and de novo synthesis compared with their breast-fed (BF) counterparts in 4-mo-old infants. The incorporation rate of deuterium in body water into erythrocyte membrane-free Ch over 48 h was used as an index of cholesterogenesis. Plasma total-Ch and LDL-Ch concentrations were highest (p < 0.02) in BF infants, compared with infants in the RF-fed groups. Infants in the RF+Ch groups showed an intermediate response; their plasma total-Ch and LDL-Ch concentrations were not significantly different from the BF or the RF-fed groups. Plasma total/HDL-Ch and LDL/HDL-Ch ratios were higher (p < 0.05) in BF, and higher in RF+Ch-fed infants, compared with those fed RF, whereas not different between BF and RF+Ch-fed infants. At 4 mo of age, Ch FSR was 4-fold lower (p < 0.0001) in BF versus other groups, but not significantly different between RF- and RF+Ch-fed infants. Thus, despite addition of Ch to the concentration found in breast milk, FSR remained elevated compared with that of the group fed breast milk, with an intermediate response in circulating Ch levels. It is speculated that factors other than Ch intake account for the differential Ch metabolism between formula-fed and BF infants.

Aluminum toxicity is associated with the development of bone disorders, including fractures, osteopenia, and osteomalacia. Fifty-one infants with a mean (+/- SEM) birth weight of 1007 +/- 34 g, gestational age of 28.5 +/- 0.3 weeks, and serial radiographic documentation at 3, 6, 9, and 12 months for the presence (n = 16) or absence (n = 35) of fractures and/or rickets were studied at the same intervals to determine the serial changes in serum aluminum concentrations and urine aluminum-creatinine ratios. Autopsy bone samples were used to determine the presence of tissue aluminum. Serum aluminum concentrations from 46 infants were stable and similar between groups, with mean values between 15 and 22 micrograms/L. Urine aluminum-creatinine (micrograms per milligram) ratios from 14 infants were higher in infants with fractures and/or rickets (0.26 +/- 0.06 vs 0.12 +/- 0.04) at onset, and rate of decrease in aluminum-creatinine ratio was faster in infants without fractures and/or rickets. All but three infants were tolerating complete enteral feeding at all sampling points. One infant who received aluminum-containing antacid had marked increase in serum aluminum to 83 micrograms/L while urine aluminum-creatinine ratio increased from 0.09 to a peak of 8.53. Vertebrae from three infants at autopsy (full enteral feeding was tolerated for 37 and 41 days in two infants, respectively) showed aluminum deposition in the zone of provisional calcification and along the newly formed trabecula.(ABSTRACT TRUNCATED AT 250 WORDS)

One hundred five children (49 male, 99 black) with known lead exposure indices from birth and adequate nutrient intake of calcium, phosphorus, and vitamin D were studied at 1 of 3 ages (21, 27, or 33 months) to determine the effects of chronic low to moderate lead exposure on circulating concentrations of vitamin D metabolites and bone mineral content as determined by photon absorptiometry. Univariate multiple regression analyses showed no direct relationship of blood lead levels to vitamin D metabolites or bone mineral content. Structural equation analyses which took into account potential covariates of age, season, race, and sex showed estimated declines in serum concentrations of total calcium (from 9.72 to 9.61 mg/dL), phosphorus (from 5.4 to 4.67 mg/dL), and 25-hydroxyvitamin D (from 27.24 to 25.8 ng/mL) and estimated increases in concentrations of parathyroid hormones (from 73.03 to 83.14 microL Eq/mL), 1,25-dihydroxyvitamin D (from 62.39 to 62.69 pg/mL), and bone mineral content (from 222.66 to 234.91 mg/cm) over the observed range of average lifetime blood lead concentrations (4.76 to 23.61 micrograms/dL, geometric mean 9.74 micrograms/dL). However, the only statistically significant effect of average lifetime blood lead concentration was that for phosphorus, and the multivariate test of the combined effects of lead on these six outcomes was not statistically significant (P = .2). It is concluded that significant alterations in vitamin D metabolism, calcium and phosphorus homeostasis, and bone mineral content are not present in children whose nutritional status is adequate and who experience low to moderate lead exposure.

Fractures and rickets (F/R) often occur in very low birth weight (VLBW less than 1500 g) infants who are acutely ill. However, there are no prospective longitudinal studies of the clinical course of F/R in these infants. In a prospective study of 78 VLBW infants during the first year after birth, radiographic evidence of healing and remodeling of F/R was noted in affected infants (n = 25) concurrent with increased enteral intake and physical growth, and regardless of whether specific orthopedic treatment was initiated. Skeletal maturation as indicated by the development of ossification centers at the wrists was directly related to weight gain, and was similar to term infants by 1 year. No infant had skeletal deformities on follow-up examination. We suggest that VLBW infants with F/R can be managed "conservatively," with emphasis on nutritional intake to achieve weight gain.

Seventy-four infants with birth weights 1009 +/- 28 grams and gestational age 28.6 +/- 0.3 weeks (M +/- SEM) were studied prospectively to test the hypotheses that bone mineral content (BMC) measured by photon absorptiometry, would be: (1) lower in very low birth weight (VLBW) infants with radiographic evidence of fractures and/or rickets (F/R), and (2) will continue to be lower over the first year when compared to VLBW infants without F/R. BMC and bone width (BW) of the distal one-third of left radius and ulna were measured at 5 weeks (n = 8), 14 weeks (n = 61), 26 weeks (n = 58), 40 weeks (n = 59), and 1 year (n = 52). Standardized radiographs of both forearms, and weight, length, and head circumference were also determined at each study age. Investigators and technicians involved in the photon absorptiometry measurements were unaware of the radiographic findings and vice versa. Twenty-three of 74 infants were found to have F/R. BMC of studied infants remained markedly below our previously determined range of "intrauterine bone mineralization," even at 26 weeks after birth. There was no significant difference in BMC or BW between infants with and without F/R, either at the time of confirmation of F/R or during early follow-up; however, BMC was lower at greater than or equal to 6 months and BW was lower at greater than or equal to 9 months in infants with F/R. We suggest that the extremely low BMC measurements in early infancy predispose all VLBW infants to fractures and rickets.