Susan Krug-Wispe

Fractures and rickets in very low birth weight infants: conservative management and outcome.

Fractures and rickets (F/R) often occur in very low birth weight (VLBW < 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.

Aluminum Contamination of Infant Formulas

This study aims to determine the extent of aluminum (Al) contamination in whole milk, milk formulas, and other nutrient products commonly used for infants. Similar products from different manufacturers and different lots were measured for Al using electrothermal atomic absorption technique. Aluminum measurements were made directly from the samples or after reconstitution or dilution with Al-free water. Aluminum content was lowest (<50 μg/liter) in human milk, whole cow milk, and products that appear to require minimal manufacture processing and have few additives such as skim milk, cow milk with 2% fat, bottled glucose water, and sterile water. Highest Al levels (up to 2346 μg/liter) were found in highly processed and modified formulas including soy formula, preterm infant formula, and formulas for specific metabolic disorders. Aluminum content of humanized cow milk formula and bottled glucose-electrolyte solution were between the two ranges and usually <400 μg/liter. There were no significant differences...

Effect of three levels of vitamin D intake in preterm infants receiving high mineral-containing milk.

Very low-birth weight (VLBW) infants fed high-calcium and high-phosphorus (10.74 and 6.93 mmol/MJ; 180 and 90 mg/100 kcal, respectively) infant formulas were randomized to one of three levels of vitamin D intake to approximate 200, 400, and 800 IU/day. Sixty-two infants completed the study (24 to 29 days), with actual mean daily vitamin D intakes of 161, 361, and 766 IU, respectively. Outcomes were not different by group: gains in body weight, length and head circumference, serum calcium, magnesium, phosphorus, alkaline phosphatase, osteocalcin, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, and urine calcium:creatinine and magnesium:creatinine ratios. There were no radiographic fractures and/or rickets. A subset of 19 infants was followed between 173 and 380 days to determine descriptively if there was any delayed effect of earlier manipulation of vitamin D intake. They were fed standard infant formulas with a vitamin D content of 400 to 420 IU/L. No significant differences were present among the three groups, and data were combined. Serum 25-hydroxyvitamin D increased (p < 0.05), osteocalcin decreased (p < 0.05), and 1,25-dihydroxyvitamin D decreased (p = 0.06) at follow-up. Thus, for VLBZW infants fed high-calcium and high-phosphorus milk, an average daily vitamin D intake as low as 160 IU maintains normal and stable vitamin D status and normal physical growth, biochemical and hormonal indexes of bone mineral metabolism, and skeletal radiographs versus randomized infants receiving about 400 or 800 IU of vitamin D per day. On follow-up, vitamin D status remained normal for > or = 6 months while infants received < 400 IU of vitamin D per day.

Minimal vitamin D and high calcium and phosphorus needs of preterm infants receiving parenteral nutrition

Preterm infants (birth weight, 1,089 ± 91 g; gestational age, 28.9 ± 0.7 weeks; mean ± SEM) with mixed medical and surgical indications for parenteral nutrition (PN) were observed to determine the adequacy of infusates with fixed, low-dose vitamin D (25 IU/dl) and two combinations of calcium and phosphorus. The duration of low-dose vitamin D PN ranged from 5 to 52 days, with a median of 27 days. Twelve infants were randomly assigned to low (standard) Ca and P doses (5 mM each; 20 mg/dl of Ca and 15.5 mg/dl of P) and 13 high Ca and P doses (15 mM each; 60 mg/dl of Ca and 46.5 mg/dl of P). The maximum daily vitamin D intake was similar for both groups (31 ± 1.3 versus 33 ± 1.2 IU/kg). Vitamin D status in either group, as indicated by serum 25-hydroxyvitamin D (25-OHD) concentrations, was normal. There was no significant difference in observed changes of serial measurements of serum calcium, magnesium, phosphorus, alkaline phosphatase, creatinine (Cr), 25-OHD, and vitamin D-binding protein concentrations or urinary Ca:Cr and Mg:Cr ratios. In the low-dose Ca and P group, the serum P level was consistently <4 mg/dl in five infants, serum 1,25-dihydroxyvitamin D concentrations were higher, and tubular reabsorption of phosphorus was consistently <95% and significantly higher than in the high-dose Ca and P groups. Severe bone demineralization apparent on X-ray occurred in two infants, with a fractured distal left ulna in one of the two infants. Abdominal ultrasonograms showed gallbladder “sludge” in six infants (four in the low-dose and two in the high dose Ca, P group) that resolved with enteral feeding. We conclude that for preterm infants receiving PN, the vitamin D requirement is minimal. A high Ca- and P-level (15 mM each) infusate may be more appropriate than low Ca and P levels (5 mM each) to maintain Ca and P homeostasis.

Influence of Formula versus Breast Milk on Cholesterol Synthesis Rates in Four-Month-Old Infants

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.

Response of Preterm Infants to Aluminum in Parenteral Nutrition

Twenty-five preterm infants with birth weights (BW) 540 to 2280 g (20 with birth weight less than 1500 g) and gestational ages 24 to 37 weeks, were studied to determine the response to 2 levels of aluminum (Al) loading from currently unavoidable contamination of various components of parenteral nutrition (PN) solution. High Al loading group (H) received solutions with measured Al content of 306 +/- 16 micrograms/liter and low A1 loading group (L) received solutions with 144 +/- 16 micrograms A1/liter. Urine Al:Creatinine (Al:Cr) ratios (micrograms:mg) became elevated and significantly higher in H (1.6 +/- 0.38 vs 0.5 +/- 0.1, p less than 0.05) at the third sampling point (mean 19 days). Serum Al concentrations were highest at onset in both groups and stabilized with study but remained consistently higher than the normal median of 18 micrograms/liter. Calculated urine Al excretion were consistently low and were 34 +/- 6% vs 28 +/- 5% in the H and L groups, respectively. One infant in the L group who died 39 days after termination of above study showed the presence of A1 in bone trabeculae and the presence of excessive unmineralized osteoid along the trabeculae. We conclude that small preterm infants are able to increase urine Al excretion with increased Al load. However urine Al excretion is incomplete with bone deposition of Al and persistently elevated serum Al concentrations.

Similar gastric emptying rates for casein- and whey-predominant formulas in preterm infants.

ABSTRACT: Casein-predominant infant milk formulas have been speculated to predispose to lactobezoar formation in preterm infants due to delayed gastric emptying. There have been, however, no prospective studies to prove this possi-bility. In a randomized, double-blinded, prospective study, we tested the hypothesis that preterm infants fed casein-predominant milk formula have slower gastric emptying than infants fed whey-predominant formulas. Twenty pre-term infants within the first 4 d of life were randomized to receive either the whey-predominant formula Similac Special Care (whey:casein ratio 60:40) or an experimental casein-predominant formula (whey:casein ratio 18:82). Only the protein composition differed between the two formulas. The infants were fed the assigned study formula until they reached approximately 2200 g body weight when a gastric emptying scan was performed, using the designated study formula mixed with 25 μCi of technetium-99 sulfur colloid. Gastric emptying was followed continuously for 2 h. Gastric emptying at 30, 60, 90, and 120 min was similar between the two study groups. The time for 50% gastric emptying was 64.9 ± 12.3 min for the infants fed the whey-predominant formula and 56.5 ± 14.8 min for those fed the casein-predominant formula (p = 0.75). We conclude that the rate of gastric emptying in preterm infants fed casein-predominant formulas is similar to that in those fed whey-predominant formulas.

Cholesterol Supplementation Effect on Cholesterol Synthesis Rates (FSR) In Infants. ▴ 679

Background: We have shown previously in infants that type of milk affects FSR. There was a 2.6 fold increase in FSR of infants fed a cow milk based formula (low cholesterl (chol), 1-3 mg/dl) vs. human milk (HUM, high chol, 9-12 mg/dl) (Pediatr Res, 35:135). The effect of chol supplementation of cow milk based formula has not been studied. Hypothesis: 1) FSR in 4 mos. old infants fed modified formula (MF) (with amounts of chol similar to that found in HUM, 13 mg/dl) will be similar to FSR of infants fed HUM, and lower than those fed regular cow milk based formula (RF). 2) There will be “imprinting” effect of lipid intake early in life on FSR later in life. Design and method: Prospective cross over study in 90 infants; recruited in first wk of life, followed until 4 mos. of age (Arm one), or until 1 yr. of age (Arm two). We report arm one data. We followed 27 infants: HUM (n=13), RF (n=7), or MF (n=7). FSR is measured on 3 consecutive days as the rate of incorporation of deuterium oxide into red cell membrane chol (J Lipid Res, 32: 1049). Serum total chol, triglyceride (trig), and high density (HDL-c), and low density lipoprotein-chol (LDL-c) were measured.Results: Data (mean ± SEM) were analyzed using ANOVA.Table Conclusions: FSR was 3.8 fold higher in cow milk based formula (RF and MF) groups vs HUM, but not different between RF and MF infants. Thus, cholesterol supplement of one cow milk based formulation to HUM levels, did not significantly reduce fractional synthesis rate of cholesterol at 4 months of age. (support by Am. Heart Assoc. and Wyeth Labs)

HIGH BONE SPECIFIC ALKALINE PHOSPHATASE IN SMALL FOR GESTATIONAL AGE VERSUS APPROPRIATE FOR GESTATIONAL AGE INFANTS, AND IN WINTER- VERSUS SUMMER-BORN NEWBORN INFANTS. † 1879

HIGH BONE SPECIFIC ALKALINE PHOSPHATASE IN SMALL FOR GESTATIONAL AGE VERSUS APPROPRIATE FOR GESTATIONAL AGE INFANTS, AND IN WINTER- VERSUS SUMMER-BORN NEWBORN INFANTS. † 1879