Parenteral fat emulsions based on olive and soybean oils: a randomized clinical trial in preterm infants

OBJECTIVE: To evaluate in premature infants a new parenteral lipid emulsion based on olive and soybean oils (ratio 4:1), with less polyunsaturated fatty acids (PUFA) and more alpha-tocopherol than standard soybean oil emulsion. STUDY DESIGN: Premature infants (gestational age, 28-<37 weeks) were randomized to receive one of the two emulsions within the first 72 hours of life. The triglyceride dose was increased to 2 g/kg/day within 3 days. Plasma phospholipid fatty acids, alpha-tocopherol/lipid ratio, and urinary malondialdehyde (MDA) excretion were determined at baseline and after 7 days. RESULTS: Of 45 recruited infants, 33 completed the study per protocol (15 soybean oil, 18 olive oil emulsion). At study end, groups did not differ in plasma phospholipid arachidonic acid, total n-6 and n-3 metabolites, but the olive oil group showed higher values of the PUFA intermediates C18:3n-6 (0.19% +/- 0.01% vs. 0.13% +/- 0.02%, P < 0.05) and C20:3n-6 (2.92% +/- 0.12% vs. 2.21% +/- 0.17%, P = 0.005). The plasma alpha-tocopherol/total lipd ratio was higher in the olive oil group (2.45 +/- 0.27 micromol/mmol vs. 1.90 +/- 0.08 micromol/mmol, P = 0.001), whereas urinary MDA excretion did not differ. CONCLUSION: The lower PUFA supply with the olive/soybean oil emulsion appears to enhance linoleic acid conversion. The reduced PUFA content, combined with a higher antioxidant intake in the olive oil group, results in an improved vitamin E status. The olive oil-based emulsion is a valuable alternative for parenteral feeding of preterm infants who are often exposed to oxidative stress, while their antioxidative defense is weak.     

The nutritional role of breast-milk IgA and lactoferrin

The nutritional enigma concerning the extent to which breast-milk immune proteins are digested has been investigated by measuring the intakes and faecal outputs of IgA and lactoferrin over 7 days in 10 exclusively breast-fed (BF) and 9 formula-fed (FF) fullterm infants at 6 and 12 weeks post-partum. BF outputs (mg/day) greatly exceeded FF values (p less than 0.001): at 6 weeks secretory-IgA BF = 160 +/- 28, FF = 14 +/- 2, lactoferrin BF = 14 +/- 2, FF = 0.9 +/- 0.1; at 12 weeks secretory-IgA BF = 94 +/- 17, FF = 25 +/- 5, lactoferrin BF = 7 +/- 1, FF = 1 +/- 0.3. Secretory-IgA represented 42% and 27% of BF faecal protein at 6 and 12 weeks compared with 6% for FF infants at both ages. BF secretory-IgA outputs were highly correlated with intakes (r = 0.83, p less than 0.001). IgA and lactoferrin outputs and the presence of faecal secretory-IgA fragments in BF and FF infants were influenced by defaecation rate, suggesting that partial degradation occurred in the large intestine. By 6 weeks post-partum only 1% lactoferrin and 17% secretory-IgA intakes appeared in the faeces and 95% breast-milk protein could be regarded as nutritionally available. The elevated BF outputs of IgA and lactoferrin relative to endogenous excretion suggest, however, that breast-milk may still make a considerable contribution to intestinal defence mechanisms after the neonatal period despite the small proportion of daily intake which escapes digestion. The protective action of IgA and lactoferrin may also depend on their site of degradation and the nature of fragments.     

A modified vitamin regimen for vitamin B2, A, and E administration in very-low-birth-weight infants

INTRODUCTION: Very-low-birth-weight (VLBW; birth weight, <1,500 g) infants receive preterm infant formulas and parenteral multivitamin preparations that provide more riboflavin (vitamin B2) than does human milk and more than that recommended by the American Society of Clinical Nutrition. VLBW infants who are not breast-fed may have plasma riboflavin concentrations up to 50 times higher than those in cord blood. The authors examined a vitamin regimen designed to reduce daily riboflavin intake, with the hypothesis that this new regimen would result in lower plasma riboflavin concentrations while maintaining lipid-soluble vitamin levels. METHODS: Preterm infants with birth weight < or =1,000 g received either standard preterm infant nutrition providing 0.42 to 0.75 mg riboflavin/kg/day (standard group), or a modified regimen providing 0.19 to 0.35 mg/kg/day (modified group). The modified group parenteral vitamin infusion was premixed in Intralipid. Enteral feedings were selected to meet daily riboflavin administration guidelines. Plasma riboflavin, vitamin A, and vitamin E concentrations were measured weekly by high-performance liquid chromatography. Data were analyzed with the independent t test, chi, and analysis of variance. RESULTS: The 36 infants (17 standard group, 19 modified group) had birth weight and gestational age of 779 +/- 29 g and 25.5 +/- 0.3 weeks (mean +/- SEM) with no differences between groups. Modified group infants received 38% less riboflavin (0.281 +/- 0.009 mg/kg/day), 35% more vitamin A (318.3 +/- 11.4 microg/kg/day), and 14% more vitamin E (3.17 +/- 0.14 mg/kg/day) than standard group infants. Plasma riboflavin rose from baseline in both groups but was 37% lower in the modified group during the first postnatal month (133.3 +/- 9.9 ng/mL). Riboflavin intake and plasma riboflavin concentrations were directly correlated. Plasma vitamin A (0.222 +/- 0.022 microg/mL) and vitamin E (22.26 +/- 1.61 /mL) concentrations were greater in the modified group. CONCLUSIONS: The modified vitamin regimen resulted in reduced riboflavin intake and plasma riboflavin concentration, suggesting plasma riboflavin concentration is partially dose dependent during the first postnatal month in VLBW infants. Modified group plasma vitamin A and vitamin E concentrations were greater during the first month, possibly because the vitamins were premixed with parenteral lipid emulsion. Because of the complexity of this protocol, the authors suggest that a parenteral multivitamin product designed for VLBW infants which uses weight-based dosing should be developed.     

Nutrient intakes of formula-fed infants and infants fed cow's milk

Twenty-four-hour dietary intake data from the second National Health and Nutrition Examination Survey (NHANES II), 1976-1980, were analyzed to compare nutrient intakes among infants 7 to 12 months of age who were fed mixed diets containing solid foods and either infant formula or cow's milk. Solid foods fed to the infants in both groups were low in iron and linoleic acid, and high in sodium, potassium, and protein, relative to Recommended Dietary Allowances. Infants who were fed cow's milk received lower median intakes of iron (7.8 mg v 14.9 mg), linoleic acid (1.8 g v 6.1 g), and vitamin C (39 mg v 64 mg), and higher median intakes of protein (41 g v 25 g), sodium (1,000 mg v 580 mg), and potassium (1,630 mg v 1,020 mg) than formula-fed infants. Seventy-five percent of the infants fed cow's milk had iron intakes below the Recommended Dietary Allowance; 69% had sodium intakes above the range of estimated safe and adequate daily dietary intake. Linoleic acid provided less than 3% of energy intake for 74% of the infants fed cow's milk. Differences in nutrient intakes were due not only to different concentrations of nutrients in each of the milk feedings but also to the different amounts and types of solid foods fed to the two groups of infants.     

Impact on iron status of introducing cow's milk in the second six months of life

To determine the impact on iron status of introducing cow's milk (CM) into the diet during the second 6 months of life, nutrient intake was assessed and iron status measured in 100 infants. Nutrient intake for 40 of the 45 infants, age 8 to 13 months, fed CM as the primary beverage for at least 3 months prior to the study and for 45 of 55 infants the same age fed a milk-based infant formula (FF) as the primary beverage for at least 3 months were assessed. All infants in the study were healthy, and the majority were taking no medications or supplements other than vitamins or fluoride for 3 weeks prior to the assessment. Blood drawn by peripheral venipuncture was analyzed by Coulter Counter for complete blood count; plasma albumin, iron, ferritin, transferrin saturation, and total iron-binding capacity were measured in all infants. CM-fed infants had significantly lower mean iron and vitamin C intakes, plasma albumin, transferrin saturation, and ferritin than did FF infants. The frequency of low plasma iron, low transferrin saturation, and low plasma ferritin was significantly greater in CM-fed than in FF infants. The percentage of subjects with three or more abnormal iron indices was more than twice as great in CM-fed infants (58%) as in FF infants (23%). Feeding infants iron-fortified formula to 12 months of age appears to deter iron deficiency.     

Evaluation of a pediatric multiple vitamin preparation for total parenteral nutrition. II. Blood levels of vitamins A, D, and E

This study represents the first attempt to evaluate the American Medical Association Nutrition Advisory Group (NAG) recommendations for intravenous vitamin A, D, and E dosages for infants and children. Patients studied included 18 preterm infants (group 1) and 26 term infants and children (group 2A) receiving total parenteral nutrition for 2 to 4 weeks and eight infants and children receiving total parenteral nutrition for 3 to 6 months (group 2B). Term gestation infants and children up to 11 years of age all received the same dosages (those that were recommended by the NAG for children weighing more than 10 kg). Preterm infants received 65% of these doses. In group 1, cord blood alpha-tocopherol levels were less than 0.22 mg/dL in seven preterm infants (reference value = 0.29 +/- 0.04), but mean levels increased to 1.65 +/- 0.17 mg/dL after four days of treatment. Eight infants consistently received additional vitamin E orally (80 to 150 mg daily), and their levels increased to 2.18 +/- 0.26 mg/dL by four days of study and to 3.49 +/- 0.57 mg/dL after 3 weeks. Oral supplementation in the preterm infants appeared to be unnecessary because intravenous vitamins alone maintained levels above 1.1 mg/dL. In group 2, alpha-tocopherol levels were maintained within the reference range. Patients receiving lipid emulsions containing substantial quantities of alpha-tocopherol had significantly higher blood levels than patients receiving lipid emulsions containing little alpha-tocopherol (P less than .01). Mean 25-OH vitamin D levels were maintained above or within the reference range in groups 2A and 2B.(ABSTRACT TRUNCATED AT 250 WORDS)     

25-hydroxyvitamin D and calcium levels in maternal, cord and infant serum in relation to maternal vitamin D intake

The plasma levels of 25-hydroxyvitamin D (25-OHD), total calcium, phosphorus and proteins were measured in 40 healthy mothers and their infants at the time of delivery during the months of December and January. Calcium, phosphorus and proteins were again measured in the plasma of the infants on the fourth day of life. Vitamin D intake of the mothers during their last 3 months of pregnancy were estimated by interviews. The mean (+/-SE) plasma levels of 25-OHD was 9.0 +/- 0.9 ng/ml in the mothers and 5.05 +/- 0.4 ng/ml in cords. There was a significant correlation between mother and cord plasma levels (r = 0.75, p less than or equal to 0.001). The concentration gradient of 25-OHD plasma levels between mother and cord is higher at high 25-OHD maternal concentrations. This suggests that the placenta plays a regulating role in the 25-OHD transfer between mother and foetus. The 4-day-old infants from mothers having a suboptimal vitamin D intake (less than 150 IU/day) have a lower mean serum plasma level than infants born from mothers with a vitamin D intake of more than 500 IU/day.     

Vitamin concentrations in very low birth weight infants given vitamins intravenously in a lipid emulsion: measurement of vitamins A, D, and E and riboflavin

Because total parenteral nutrition with vitamins added to the glucose-amino acid mixture is often associated with a reduction in blood levels of vitamin A (retinol) during the routine treatment of many very low birth weight (VLBW) infants (less than 1500 gm), and because retinol losses in the plastic delivery system can be prevented by adding the vitamins to an intravenous lipid emulsion, seven VLBW infants with a mean birth weight of 900 gm (range 450 to 1360 gm) were given 40% of a unit dose vial, per kilogram of body weight, of a multivitamin preparation (M.V.I. Pediatric) (280 micrograms retinol; 160 IU vitamin D; 2.8 mg tocopherol; 0.68 mg riboflavin) in a lipid emulsion, Intralipid. After treatment with the intralipid-vitamin mixture for 19 to 28 days, plasma vitamin A (retinol) concentrations increased significantly from 11.0 +/- 0.76 (mean +/- SEM) before intralipid to 19.2 +/- 0.97 micrograms/dl after the intralipid-vitamin mixture (p less than 0.01); 25-hydroxyvitamin D concentrations increased from an initial value of 12.6 +/- 2.6 to 20.2 +/- 1.9 mg/dl (p less than 0.01); alpha-tocopherol concentrations increased from an initial value of 0.31 +/- 0.06 to 2.44 +/- 0.13 mg/dl (p less than 0.01); and riboflavin levels increased from 64.1 +/- 7.8 ng/ml to concentrations between 20 and 100 times the initial level. Erythrocyte riboflavin levels increased from 71.8 +/- 14 initially to 166 +/- 41 ng/gm hemoglobin, and erythrocyte flavin-adenine dinucleotide levels increased similarly from 972 +/- 112 initially to 2005 +/- 294 ng/gm hemoglobin. These results show that the addition of M.V.I. Pediatric to Intralipid decreases the extensive in vivo loss of retinol and is associated with an increase in plasma retinol concentrations in VLBW infants. The daily doses of vitamins D (160 IU/kg) and E (2.8 mg/kg) appear sufficient, but the dose of vitamin A (280 micrograms/kg) is insufficient to raise blood levels of all infants into the normal range. The current dose of riboflavin is excessive and may be harmful.     

Vitamin K status of lactating mothers, human milk, and breast-feeding infants

Hemorrhagic disease of the newborn is a disease of breast-feeding newborns. There is little information on longitudinal breast milk concentrations of phylloquinone (vitamin K1) or the effects of maternal phylloquinone supplements on breast milk. In study part 1, 11 lactating mothers, who received 20 mg of phylloquinone orally, had rises in plasma (less than 1 to 64.2 +/- 31.5 ng/mL by 6 hours) and breast milk concentrations (from 1.11 +/- 0.82 to 130 +/- 188 ng/mL by 12 hours). In part 2, 23 lactating mothers and their infants were observed longitudinally along with a formula-fed control group of infants (n = 11). Mean breast milk concentrations of phylloquinone at 1, 6, 12, and 26 weeks were 0.64 +/- 0.43, 0.86 +/- 0.52, 1.14 +/- 0.72, and 0.87 +/- 0.50 ng/mL, respectively, in the infants fed human milk. Maternal phylloquinone intakes (72-hour dietary recalls) exceeded the recommended daily allowance of 1 microgram/kg per day. Infant phylloquinone intakes did not achieve the recommended daily allowance of 1 microgram/kg per day in any infant. Plasma phylloquinone concentrations in the infants fed human milk remained extremely low (mean less than 0.25 ng/mL) throughout the first 6 months of life compared with the formula-fed infants (4.39 to 5.99 ng/mL). In this small sample, no infant demonstrated overt vitamin K deficiency. Despite very low plasma phylloquinone concentrations, vitamin K supplements (other than in the immediate newborn period) cannot be recommended for exclusively breast-fed infants based on these data.     

Erythrocyte lipid abnormalities in Reye's syndrome

Previous studies have demonstrated alterations in plasma free fatty acid content in Reye's syndrome (RS). We have therefore studied erythrocyte membrane lipids to determine if there are concomitant structural and functional modifications attributable to RS. Erythrocyte lipids were measured in children with RS and in critically ill children also requiring intensive care (ICU). In comatose RS patients erythrocyte phospholipid arachidonate was increased 2-fold relative to control ICU patients: 20.46 +/- 2.14 versus 10.41 +/- 2.32% of total erythrocyte phospholipid, p less than 0.05. RS coma patients also demonstrated an increased ratio of erythrocyte phospholipid polyunsaturated/saturated fatty acids (0.76 +/- 0.10) compared to ICU controls (0.48 +/- 0.08, p less than 0.05). Erythrocyte cholesterol was higher in RS patients (79.00 +/- 6.61 micrograms/mg protein) than in ICU controls (59.74 +/- 6.09, p less than 0.05). Erythrocyte malondialdehyde generation was decreased in comatose RS patients (404 +/- 28 nmol malondialdehyde/g hemoglobin) versus ICU (517 +/- 29, p less than 0.05). Although plasma vitamin E was depressed in RS patients, the erythrocyte vitamin E concentrations were no different in RS patients than in ICU patients. All RS patients had a typical viral prodrome and either a history of aspirin intake and/or measurable serum salicylate on admission. All of the biochemical abnormalities in RS patients listed above returned to values comparable to those of healthy RS siblings on recovery. The transient nature of these phenomena suggests that they were related to viral infection and/or aspirin rather than to intrinsic differences in lipid metabolism between RS patients and controls.     

Supplementation of pooled human milk with casein hydrolysate: energy and nitrogen balance and weight gain composition in very low birth weight infants

Growth and nitrogen and energy balances were studied with a combined technique of nutrient balance and indirect calorimetry measurement in two groups of eight very low birth weight infants fed pooled pasteurized human milk (HM) or cow's milk casein hydrolysate supplemented HM (HM-Pr). There was no difference in the amount of energy absorbed (91 +/- 17 kcal/kg/day with HM-Pr versus 95 +/- 8 with HM-P) or in the growth rate. The infants fed HM-Pr had a higher nitrogen intake (602 +/- 80 versus 395 +/- 64 mg/kg/day; p less than 0.001), urinary nitrogen excretion (160 +/- 64 versus 78 +/- 16 mg/kg/day; p less than 0.005) and nitrogen retention (326 +/- 32 versus 252 +/- 48 mg/kg/day; p less than 0.01). They also had increased plasma concentrations of essential amino acids, urea nitrogen, and total protein without metabolic imbalance. Energy expenditure was higher (58 versus 49 kcal/kg/day; p less than 0.005) and energy storage lower (33 versus 47 kcal/kg/day; p less than 0.05) with HM-Pr. In percent of weight gain, protein and fat accretion represented 12 and 14% in HM-Pr group versus 10 and 27% in HM group. Very low birth weight infants fed casein hydrolysate supplemented pooled HM achieved a growth rate and a weight gain composition similar to the fetus.     

Zinc homeostasis in healthy infants fed a casein hydrolysate formula

BACKGROUND: The results of earlier, nonquantitative studies suggested that absorption of zinc from a semielemental (casein hydrolysate) formula was inferior to absorption from a cow's milk-based formula. The objective of this study was to compare fractional, total and net zinc absorption, and fecal excretion of endogenous zinc in the same healthy young infants when fed a casein hydrolysate versus cow's milk-based formula. METHODS: Fractional absorption of zinc and fecal excretion of endogenous zinc were determined from measurement of cumulative fecal excretion of unabsorbed tracer and by an isotope dilution technique, respectively, after oral administration of a 70Zn tracer with all formula feedings for 1 day. Six infants were assigned randomly to receive the test or control formula, and the other formula was administered 2 to 5 weeks later. RESULTS: Mean (+/-SD) fractional absorption of zinc from the casein hydrolysate formula (0.47 +/- 0.17) was double that from the cow's milk-based formula (0.22 +/- 0.04; P = 0.01) with a correspondingly greater total zinc absorption (3.23 +/- 1.67 mg Zn/day vs. 1.55 +/- 0.55 mg Zn/day; P = 0.05). Because the excretion of endogenous zinc in the feces did not differ between formulas (0.90 +/- 0.44 mg Zn/day vs. 0.91 +/- 0.29 mg Zn/day), net absorption of zinc was also higher with the casein hydrolysate formula (2.33 +/- 1.65 mg Zn/day vs. 0.81 +/- 0.67 mg Zn/day; P = 0.02). CONCLUSIONS: Retention of zinc appeared to be adequate to meet the needs for growth during feeding with cow's milk-based formula and was more than adequate during short-term feeding with the casein hydrolysate formula.     

The Nutritional Role of Breast-Milk IgA and Lactoferrin

ABSTRACT. The nutritional enigma concerning the extent to which breast-milk immune proteins are digested has been investigated by measuring the intakes and faecal outputs of IgA and lactoferrin over 7 days in 10 exclusively breast-fed (BF) and 9 formula-fed (FF) fullterm infants at 6 and 12 weeks post-partum. BF outputs (mg/day) greatly exceeded FF values ( p <0.001): at 6 weeks secretory-IgA BF=160±28, FF=14±2, lactoferrin BF=M±2, FF=0.9±0.1; at 12 weeks secretory-IgA BF=94±17, FF=25±5, lactoferrin BF=7±1, FF=1±0.3. Secretory-IgA represented 42% and 27% of BF faecal protein at 6 and 12 weeks compared with 6% for FF infants at both ages. BF secretory-IgA outputs were highly correlated with intakes ( r =0.83, p <0.001). IgA and lactoferrin outputs and the presence of faecal secretory-IgA fragments in BF and FF infants were influenced by defaecation rate, suggesting that partial degradation occurred in the large intestine. By 6 weeks post-partum only 1% lactoferrin and 17% secretory-IgA intakes appeared in the faeces and 95% breast-milk protein could be regarded as nutritionally available. The elevated BF outputs of IgA and lactoferrin relative to endogenous excretion suggest, however, that breast-milk may still make a considerable contribution to intestinal defence mechanisms after the neonatal period despite the small proportion of daily intake which escapes digestion. The protective action of IgA and lactoferrin may also depend on their site of degradation and the nature of fragments.     

The effect of fish oil supplementation on heart rate in healthy Danish infants

Polyunsaturated n-3 fatty acids (n-3PUFA) may improve brain development and prevent cardiovascular disease. Heart rhythm is autonomically controlled and among the affected cardiovascular risk markers in adults. The aim of the study was to examine whether fish oil supplementation in late infancy could modify heart rate (HR) and heart rate variability (HRV). In a 2 x 2-intervention, 83 healthy Danish infants were randomized to +/- fish oil (3.4 +/- 1.1 mL/d) and cow's milk or infant formula from 9 to 12 mo of age. In 57 infants, 0.5-h ECG recordings were successfully obtained before and after the intervention and erythrocyte fatty acid composition was determined in 30 of these. Fish oil supplementation raised erythrocyte n-3PUFA content (p < 0.001). No significant group differences were seen in HR or HRV. However, a fish-oil x gender interaction was observed on mean RR interval (p = 0.001) with a 6% longer mean RR interval in fish-oil-supplemented boys (p = 0.007). Irrespective of gender, there was a positive association between the 9- and 12-mo changes in RR interval and erythrocyte n-3PUFA (p < 0.001). In infants with confirmed changes in erythrocyte n-3PUFA, mean RR interval was found to be longer (p = 0.011) in the fish-oil-supplemented groups. The study suggests that fish oil may affect heart rhythm in infants similar to that observed in adults. This may imply low n-3PUFA-status in late infancy and n-3PUFA influence on CNS function.     

Formula intake of 1- and 4-month-old infants

This study was designed to estimate energy intake in exclusively formula-fed infants. Formula intake of twenty-four 1- and 4-month-old infants was studied for 5 consecutive days; six boys and six girls were in each age group. Intake was estimated by laboratory-determined weights of formula consumed, spilled, and regurgitated. Two additional methods were used to estimate intake in the first nine infants during the 1st day of observation: test-weighing the infant at each feeding and mother's weighing of formula consumed, regurgitated, and spilled at each feeding. No consistent differences were detected among methods, but test-weighing appeared to have the greatest feed-to-feed variability. Intake was estimated to be 747 +/- 100 g or 125.5 +/- 17 kcal/kg, and 958 +/- 131 g or 94.0 +/- 13 kcal/kg for 1- and 4-month-old infants, respectively. The day-to-day variability (expressed as the coefficient of variation) was 13 and 15% (CV, g/kg) for 1- and 4-month-old infants, respectively. Between-infant variability of intake was approximately 8% (CV, g/kg) for both age groups. Energy intakes of 1-month-old formula-fed infants were similar to published values of breast-fed infants of similar age, but the energy intakes of 4-month-old formula-fed infants were significantly higher than values published for 4-month-old breast-fed infants.     

Total parenteral nutrition in sick preterm infants: effects of cysteine supplementation with nitrogen intakes of 240 and 400 mg/kg/day

The effects of supplementing total parenteral nutrition (TPN) solutions with cysteine were assessed at two different levels of nitrogen intake by determining nitrogen retention, sulfate excretion, and sulfur-containing amino acid concentrations. Ten infants received 72 mg/kg/day of cysteine-HCl in a TPN solution for a period of 6 days. Five of these infants received 251 +/- 48 (mean +/- SD) mg/kg/day of nitrogen, and five received 403 +/- 45 mg/kg/day of nitrogen. Two other groups of five infants each received unsupplemented TPN at nitrogen intakes of 235 +/- 48 and 412 +/- 54 mg/kg/day, respectively. Fluid and nonprotein caloric intakes were similar for all four groups. Cysteine supplementation increased plasma and urine free cyst(e)ine concentrations and enhanced total sulfur retention, but did not enhance nitrogen retention. [Cyst(e)ine refers to the mixture in any proportion of the sulfhydryl (cysteine) and the disulfide (cystine) forms of this compound.] Nitrogen retention, sulfate excretion, cyst(e)ine excretion, and plasma taurine concentrations increased as the result of the increase in nitrogen intake.     

Serum vitamin D metabolites in very low birth weight infants with and without rickets and fractures

Seventy-one very low birth weight (less than or equal to 1500 gm) infants were studied to determine the sequential changes in serum vitamin D metabolite concentrations between infants with and without radiographically documented rickets, fractures, or both (R/F). Usual intake of vitamin D included 20 IU/kg/day from parenteral nutrition or 400 IU/day supplementation with enteral feeding. Radiographs of both forearms and serum samples were obtained at 3, 6, 9, and 12 months. Twenty-two infants had R/F. At 3 months, significantly lower mean (+/- SEM) serum phosphorus levels (4.5 +/- 0.4 vs 6.1 +/- 0.2 mg/dl), higher 1,25-dihydroxyvitamin D (1,25-[OH]2D) concentrations (96 +/- 5 vs 77 +/- 4 pg/ml), and higher free 1,25-(OH)2D index (1,25-[OH]2D:vitamin D binding protein ratio; 5.2 +/- 0.3 x 10(5) vs 4.0 +/- 0.2 x 10(5] were found in the R/F group. These values returned to normal and were similar between groups on subsequent measurements. Serum calcium, magnesium, and 25-hydroxyvitamin D (25-OHD) concentrations were normal and similar between groups. In both groups, serum vitamin D binding concentrations increased initially but remained stable and normal beyond 6 months. We conclude that in very low birth weight infants with R/F, the vitamin D status (as indicated by serum 25-OHD concentrations) is normal, and that lowered serum phosphorus levels, higher serum 1,25-(OH)2D levels, and a higher free 1,25-(OH)2D index support the thesis that mineral deficiency (especially of phosphorus) may be important in the pathogenesis of R/F in small preterm infants.     

The plasma levels of 25-hydroxyvitamin D in patients with various liver diseases and the response of 25-hydroxyvitamin D to vitamin D treatment.

The mean plasma levels of 25-hydroxyvitamin D (25-OH-D) were measured before and after the administration of 2000 units of daily oral vitamin D2 for a period of 2 weeks in 9 normal infants and children, 7 infants with neonatal hepatitis and persistent neonatal hepatitis, and 4 infants with congenital biliary atresia. The mean plasma level of 25-OH-D increased significantly from 19.5 +/- 3.7 (S.E.) ng/ml to 34.0 +/- 6.8 (S.E.) ng/ml after administration of vitamin D2 in controls (p less than 0.05). The mean plasma level of 25-OH-D also increased from 8.0 +/- 2.1 (S.E.) ng/ml to 22.1 +/- 2.6 (S.E.) ng/ml after vitamin D treatment in hepatitis group (p less than 0.05). In patients with congenital biliary atresia, vitamin D treatment did not affect eh plasma levels of 25-OH-D.     

Role of the source of phosphate salt in improving the mineral balance of parenterally fed low birth weight infants

Because the monobasic potassium phosphate salt (monobasic) improves the solubility of calcium and phosphorus in amino acid plus dextrose solutions, compared with the current mixtures of monobasic plus dibasic salts (dibasic), we tested the bioavailability and clinical effects of monobasic in 16 parenterally fed low birth weight infants at standard (n = 8) and high levels (n = 8) of mineral intakes. A constant infusion of macronutrients and vitamin D was provided in a crossover design of two four-day periods. With standard intakes of calcium (35 mg/kg/day, 0.9 mmol/kg/day) and phosphorus (30 mg/kg/day, 1 mmol/kg/day), there was no difference between monobasic and dibasic regimens on balance data or plasma biochemical monitoring (calcium, phosphorus, pH, carbon dioxide pressure, base excess, 1,25-dihydroxyvitamin D, 25-hydroxyvitamin D). With the use of the monobasic regimen, the mineral intakes were doubled without precipitation in the infusate: calcium, 70 mg/kg/day (1.8 mmol/kg/day), and phosphorus, 55 mg/kg/day (1.7 mmol/kg/day). This led to increased apparent retention of both calcium (63 +/- 5 mg/kg/day, 1.58 +/- 0.12 mmol/kg/day) and phosphorus (52 +/- 4 mg/kg/day, 1.67 +/- 0.14 mmol/kg/day) compared with that for standard levels of mineral intake. The improvement of calcium-phosphorus balance was accompanied by more severe calciuria (9 +/- 2 mg/kg/day, 0.2 +/- 0.05 mmol/kg/day) and by metabolic compensation for an increased acid load. In addition to the possibility of exceeding the buffering capacity of the infant, this relative acidosis could also be evidence of improved bone mineralization.     

Effect of sustained pharmacologic vitamin E levels on incidence and severity of retinopathy of prematurity: a controlled clinical trial

The incidence and severity of retinopathy of prematurity (ROP) as affected by vitamin E prophylaxis at pharmacologic serum levels (5 mg/dl) were evaluated in a double-masked clinical trial of infants with a birth weight less than or equal to 2000 gm or a gestational age less than or equal to 36 weeks. The infants were enrolled by age 5 days and randomly assigned to receive parenterally administered, and later orally administered, free alpha-tocopherol (vitamin E) or its placebo. Study medication was continued until retinal vascularization was complete or active ROP had subsided, except in infants with a diagnosis of severe disease, in whom vitamin E was substituted for study medication. Acute ROP data were collected on 755 infants. Logistic regression analysis, with control for immaturity, oxygen exposure, and other illness risk factors, showed a decrease in incidence of ROP in vitamin E-treated infants (p = 0.003, all infants; p = 0.035, infants weighing less than or equal to 1500 gm at birth). Among the 424 infants weighing less than or equal to 1500 gm at birth, the age at enrollment influenced treatment effect (age day 0 to 1, p = 0.006 (n = 288) vs age day 2 to 5, p greater than 0.1 (n = 136]. Overall, 77.6% of infants with ROP had mild disease. Moderate to severe ROP was confined to infants weighing greater than or equal to 1500 gm at birth (25 given placebo, 25 given vitamin E), with progression to severe disease in nine placebo-treated versus three vitamin E-treated infants (p = 0.048). The incidence of severe ROP per se was not significantly decreased (all birth weights, p = 0.086; less than or equal to 1500 gm birth weight, p = 0.080); the sample size was too small, however, to assess this end point adequately. An increased incidence of sepsis and late-onset necrotizing enterocolitis was found among vitamin E-treated infants weighing less than or equal to 1500 gm at birth who received study medication for greater than or equal to 8 days (p = 0.006). Because most ROP is mild in degree and regresses completely, the risk/benefit ratio of pharmacologic prophylaxis for ROP is unfavorable. Treatment of moderate and severe ROP with vitamin E above physiologic serum levels (greater than 3 mg/dl) appears promising and should be further investigated. The interpretation of cicatricial outcome was confounded by the small number of patients involved and by subsequent treatment of severe ROP in placebo-treated infants with vitamin E.