Effect of Enteral Protein Amount on Growth and Health Outcomes in Very-Low-Birth-Weight Preterm Infants: Phase II of the Pre-B Project and an Evidence Analysis Center Systematic Review.

Adequate protein intake by very-low-birth-weight preterm infants (≤1,500 g at birth) is essential to optimize growth and development. The estimated needs for this population are the highest of all humans, however, the recommended intake has varied greatly over the past several years. A literature search was conducted in PubMed, Embase, CINAHL (Cumulative Index to Nursing and Allied Health Literature), and Cochrane Central databases to identify randomized controlled trials evaluating the effect of prescribed protein intake and identified outcomes. Articles were screened by 2 reviewers, risk of bias was assessed, data were synthesized quantitatively and narratively, and each outcome was separately graded for certainty of evidence. The literature search retrieved 25,384 articles and 2 trials were included in final analysis. No trials were identified that evaluated effect of protein amount on morbidities or mortality. Moderate certainty evidence found a significant difference in weight gain when protein intake of greater than 3.5 g/kg/day from preterm infant formula was compared with lower intakes. Low-certainty evidence found no evidence of effect of protein intake of 2.6 vs 3.1 vs 3.8 g/kg/day on length, head circumference, skinfold measurements, or mid-arm circumference. Low-certainty evidence found some improvement in development measures when higher protein intake of 3.8 vs 3.1 vs 2.6 g/kg/day were compared. Low-certainty evidence found no significant difference in bone mineral content when these protein intakes were compared. No studies were identified that compared protein intake greater than 4.0 g/kg/day. This systematic review found that protein intake between 3.5 and 4.0 g/kg/day promotes weight gain and improved development.

Essential Fatty Acid Deficiency with SMOFlipid Reduction in an Infant with Intestinal Failure-Associated Liver Disease.

Multicomponent lipid emulsions, such as SMOFlipid, contain intermediate amounts of essential fatty acids (EFAs) compared with traditional soybean-oil based lipid emulsions and 100% fish-oil lipid emulsions. We describe the development of moderate EFA deficiency (EFAD) and slow weight gain in an infant with intestinal failure-associated liver disease managed with SMOFlipid reduction (1 g/kg/d). Once SMOFlipid dosage was increased (2-3 g/kg/d), EFA levels normalized, adequate growth resumed, and the infant's cholestasis resolved. We recommend avoiding lipid reduction of SMOFlipid, which not only increases the risk for EFAD, but also is unnecessary given that cholestasis can be reversed on conventional doses of SMOFlipid.

Zinc and copper requirements in preterm infants: an examination of the current literature.

BACKGROUND: Zinc and copper are essential for preterm infants, but recommended requirements from different groups vary widely. Recommended zinc intakes have steadily increased over the years. Although this would be expected to impair copper absorption, recommended copper intakes have not risen in parallel. OBJECTIVES: To systematically review the literature on zinc and copper retention in preterm infants; to examine the effect on zinc intake on copper retention; and to estimate the zinc and copper intakes required to meet the levels of zinc and copper retention required for normal growth. DESIGN: Studies reporting zinc and/or copper retention in preterm infants (<36 weeks of gestation) during the first 120 days of life were identified using PubMed. Only studies reporting net retention were included. RESULTS: Fourteen studies on zinc retention reporting data on 45 different groups were identified. Eleven studies (32 groups) were identified reporting copper retention. Zinc retention was significantly higher at higher zinc intakes, and higher in formula-based diets than in human milk based diets. Zinc intakes of between 1.8-2.4 mg/kg/d (from formula based diets) and 2.3-2.4 mg/kg/d (from human-milk based diets) were required to achieve adequate zinc retention. Copper retention was significantly positively correlated with copper intake and significantly negatively correlated with zinc intake. At the zinc intakes suggested previously (1.8-2.4, 2.3-2.4 mg/kg/d), copper intakes of between 200 and 250 mcg/kg/d are required to ensure adequate copper retention. CONCLUSIONS: Our results support the higher zinc intakes recommended in recent guidelines. However, they suggest that recommended copper intakes have not kept pace with increasing zinc intakes, and that preterm infants may need higher copper intakes than currently recommended.

Low zinc status and absorption exist in infants with jejunostomies or ileostomies which persists after intestinal repair.

There is very little data regarding trace mineral nutrition in infants with small intestinal ostomies. Here we evaluated 14 infants with jejunal or ileal ostomies to measure their zinc absorption and retention and biochemical zinc and copper status. Zinc absorption was measured using a dual-tracer stable isotope technique at two different time points when possible. The first study was conducted when the subject was receiving maximal tolerated feeds enterally while the ostomy remained in place. A second study was performed as soon as feasible after full feeds were achieved after intestinal repair. We found biochemical evidence of deficiencies of both zinc and copper in infants with small intestinal ostomies at both time points. Fractional zinc absorption with an ostomy in place was 10.9% ± 5.3%. After reanastamosis, fractional zinc absorption was 9.4% ± 5.7%. Net zinc balance was negative prior to reanastamosis. In conclusion, our data demonstrate that infants with a jejunostomy or ileostomy are at high risk for zinc and copper deficiency before and after intestinal reanastamosis. Additional supplementation, especially of zinc, should be considered during this time period.

Orange but not apple juice enhances ferrous fumarate absorption in small children.

OBJECTIVE: Ferrous fumarate is a common, inexpensive iron form increasingly used instead of ferrous sulfate as a food iron supplement. However, few data exist as to whether juices enhance iron absorption from ferrous fumarate. SUBJECTS AND METHODS: We studied 21 children, ages 4.0 to 7.9 years using a randomized crossover design. Subjects consumed a small meal including a muffin containing 4 mg Fe as ferrous fumarate and either apple (no ascorbic acid) or orange juice (25 mg ascorbic acid). They were separately given a reference dose of Fe (ferrous sulfate) with ascorbic acid. RESULTS: Iron absorption increased from 5.5% +/- 0.7% to 8.2% +/- 1.2%, P < 0.001 from the muffins given with orange juice compared with muffins given with apple juice. The absorption of ferrous fumarate given with orange juice and enhancement of absorption by the presence of juice were significantly positively related to height, weight, and age (P < 0.01 for each). Although iron absorption from ferrous fumarate given with apple juice was significantly inversely associated with the (log transformed) serum ferritin, the difference in absorption between juice types was not (P > 0.9). CONCLUSIONS: These data demonstrate an overall benefit to iron absorption from ferrous fumarate provided with orange juice. The effect was age related such that in children older than 6 years of age, there was a nearly 2-fold increase in iron absorption from ferrous fumarate given with orange juice.

An inulin-type fructan enhances calcium absorption primarily via an effect on colonic absorption in humans.

Calcium absorption efficiency and bone mineral mass are increased in adolescents who regularly consume inulin-type fructans (ITF). The mechanism of action in increasing absorption is unknown but may be related to increased colonic calcium absorption. We conducted a study in young adults designed to evaluate these mechanisms with a kinetic technique using (42)Ca orally and (46)Ca dosed i.v. Those who responded to 8 wk of supplementation with 8 g of a mixed short and long degree of polymerization ITF by increasing their calcium absorption had kinetic measurements analyzed to evaluate the time course of absorption. The area under the curve of the oral tracer in the blood during the 26 h after dosing was calculated and the time dependence of increased absorption determined. Eight young adults (of 13 studied), with mean calcium intake approximately 900 mg/d, responded to the ITF with an increased calcium absorption of at least 3%. In responders, absorption increased from 22.7 +/- 11.3% to 31.0 +/- 15.3%. Colonic absorption, defined as absorption that occurred >7 h after oral dosing, represented 69.6 +/- 18.6% of the increase, or 49 +/- 28 mg/d. These findings suggest that, in those who respond to ITF, its effects on calcium absorption occur principally in the colon. This benefit to ITF may be especially important when absorption in the small intestine is impaired for anatomic or physiological reasons.

Effect of prebiotic supplementation and calcium intake on body mass index.

OBJECTIVE: To assess the effects of a prebiotic supplement and usual calcium intake on body composition changes during pubertal growth. STUDY DESIGN: We measured anthropometry and body fat with dual-energy X-ray absorptiometry in 97 young adolescents who were randomized to receive either a daily prebiotic supplement or maltodextrin (control) for 1 year. RESULTS: Subjects who received the prebiotic supplement had a smaller increase in body mass index (BMI) compared with the control group (BMI difference 0.52 +/- 0.16 kg/m2, P = .016), BMI Z-score (difference 0.13 +/- 0.06, P = .048) and total fat mass (difference 0.84 +/- 0.36 kg, P = .022). The prebiotic group maintained their baseline BMI Z-score (0.03 +/- 0.01, paired t test, P = .30), although BMI Z-score increased significantly in the control group (0.13 +/- 0.03, P < .001). In considering subjects whose usual calcium intake was > or = 700 mg/d, those who received the prebiotic supplement had a relative change in BMI that was 0.82 kg/m2 less than control subjects (P < .01), and BMI Z-score that was 0.20 less than control subjects (P = .003). Differences tended to be maintained 1 year after supplementation was stopped. CONCLUSION: Prebiotic supplementation and avoidance of a low calcium intake can have significant effects in modulating BMI and other body composition changes during puberty.

Nutritional assessment in preterm infants.

If the aim of nutritional assessment of preterm infants is to identify suboptimal (or excessive) provision of protein, energy and micronutrients, most currently available methods perform poorly. Assessment of body weight is limited by the confounding effect of fluid status especially in the first few days of life, and measurements of linear growth are relatively imprecise and slow to respond to nutritional changes. Growth assessment is hampered by the lack of an adequate reference standard. Comparisons to historical cohorts of preterm babies are inadequate. As most very low birth weight infants leave hospital below the 10th centile, use of these charts as "standards" almost guarantees that preterm infants will have poor growth. Growth centiles based on data from newborn preterm infants have certain advantages. However, this is hardly normative data as preterm birth is always an abnormal event. Methods of assessing body composition are largely limited to the research setting, and it remains unclear whether the optimum composition of postnatal growth is one that mimics fetal growth or postnatal growth of the term infant. Biochemical nutritional assessments are of limited utility except in the highest-risk preterm infants, when nutritional inadequacy is likely (severe fluid restriction) or where intake is difficult to assess (use of human milk).

Relationships among vitamin D levels, parathyroid hormone, and calcium absorption in young adolescents.

BACKGROUND: Evidence suggests that vitamin D status in adults, as assessed by serum 25-hydroxyvitamin D (25-OHD), is positively associated with calcium absorption fraction and inversely associated with serum PTH. Few comparable pediatric data exist. OBJECTIVES: The objective of this study was to evaluate the relationships among vitamin D status, PTH, and calcium absorption in midpubertal boys and girls. METHODS: Calcium absorption was measured as part of an evaluation of the effects of prebiotics (inulin-type fructans) using a stable isotope method in 93 young adolescents, 12.7 +/- 1.0 yr of age, receiving diets averaging approximately 900 mg/d calcium. RESULTS: A significant positive relation to calcium absorption was found for serum 1,25-dihydroxyvitamin D (P = 0.048) and PTH (P = 0.007), but not for 25-OHD (P = 0.77). PTH was significantly inversely related to 25-OHD and was positively related to serum 1,25-dihydroxyvitamin D and osteocalcin. PTH was marginally significantly inversely related to lumbar spinal, but not whole body, bone mineral density. CONCLUSIONS: These data suggest that in adolescents, especially in the presence of vitamin D insufficiency, PTH secretion increases to adapt to higher rates of bone formation associated with growth. This results in higher serum 1,25(OH)2D concentrations and increased calcium absorption results. Vitamin D status, as reflected by the serum 25-OHD level, is not closely related to calcium absorption. Whether adaptation to low serum 25-OHD is adequate under physiologically stressful situations, including those leading to very low serum 25-OHD levels, is unknown.

A combination of prebiotic short- and long-chain inulin-type fructans enhances calcium absorption and bone mineralization in young adolescents.

BACKGROUND: Short-term studies in adolescents have generally shown an enhancement of calcium absorption by inulin-type fructans (prebiotics). Results have been inconsistent; however, and no studies have been conducted to determine whether this effect persists with long-term use. OBJECTIVE: The objective was to assess the effects on calcium absorption and bone mineral accretion after 8 wk and 1 y of supplementation with an inulin-type fructan. DESIGN: Pubertal adolescents were randomly assigned to receive 8 g/d of a mixed short and long degree of polymerization inulin-type fructan product (fructan group) or maltodextrin placebo (control group). Bone mineral content and bone mineral density were measured before randomization and after 1 y. Calcium absorption was measured with the use of stable isotopes at baseline and 8 wk and 1 y after supplementation. Polymorphisms of the Fok1 vitamin D receptor gene were determined. RESULTS: Calcium absorption was significantly greater in the fructan group than in the control group at 8 wk (difference: 8.5 +/- 1.6%; P < 0.001) and at 1 y (difference: 5.9 +/- 2.8%; P = 0.04). An interaction with Fok1 genotype was present such that subjects with an ff genotype had the least initial response to fructan. After 1 y, the fructan group had a greater increment in both whole-body bone mineral content (difference: 35 +/- 16 g; P = 0.03) and whole-body bone mineral density (difference: 0.015 +/- 0.004 g/cm(2); P = 0.01) than did the control group. CONCLUSION: Daily consumption of a combination of prebiotic short- and long-chain inulin-type fructans significantly increases calcium absorption and enhances bone mineralization during pubertal growth. Effects of dietary factors on calcium absorption may be modulated by genetic factors, including specific vitamin D receptor gene polymorphisms.

Ferrous sulfate is more bioavailable among preschoolers than other forms of iron in a milk-based weaning food distributed by PROGRESA, a national program in Mexico.

After 1 y of distributing a milk-based fortified weaning food provided by the Mexican social program PROGRESA, positive effects on physical growth, prevalence of anemia, and several vitamin deficiencies were observed. There was no effect on iron status, which we hypothesized was related to the poor bioavailability of the reduced iron used as a fortificant in PROGRESA. The objective of this study was to compare the iron bioavailability from different iron sources added as fortificants to the weaning food. Children (n = 54) aged 2-4 y were randomly assigned to receive 44 g of the weaning food fortified with ferrous sulfate, ferrous fumarate, or reduced iron + Na(2)EDTA. Iron absorption was measured using an established double-tracer isotopic methodology. Iron absorption from ferrous sulfate (7.9 +/- 9.8%) was greater than from either ferrous fumarate (2.43 +/- 2.3%) or reduced iron + Na(2)EDTA (1.4 +/- 1.3%) (P < 0.01). The absorption of log-(58)Fe sulfate given with the iron source correlated with serum ferritin (s-ferritin) concentration (n = 13, r = 0.63, P = 0.01) and log-(57)Fe absorption (reference dose) (n = 14, r = -0.52, P = 0.02). Absorption from ferrous fumarate and reduced iron + Na2EDTA did not correlate with s-ferritin or absorption of (57)Fe. The recommended daily portion of the fortified complementary food provides an average of 0.256, 0.096, 0.046 mmol (1.44, 0.54, and 0.26 mg) of absorbed iron, if fortified with sulfate, fumarate and reduced iron + Na(2)EDTA, respectively. Ferrous sulfate was more bioavailable than either ferrous fumarate or reduced iron + Na(2)EDTA when added to the milk-based fortified food and more readily met the average daily iron requirements for children 2-3 y of age.

Bioavailability of iron and zinc from a multiple micronutrient-fortified beverage.

OBJECTIVE: To test the hypothesis that micronutrient beverages can provide the daily iron and zinc needs of small children. STUDY DESIGN: Forty children aged 6 to 9 years were recruited (Lima, Peru). For 4 weeks, they received a daily serving of a beverage containing multiple micronutrients. Over 2 consecutive days, subjects received stable isotope-labeled servings of the beverage with and without a meal as well as an intravenous dose of zinc. Iron and zinc bioavailability were assessed using mass spectrometry. RESULTS: Iron absorption was significantly lower with a meal than without (9.8 +/- 6.7% versus 11.6 +/- 6.9%, P=.04), but zinc absorption was not (24.5 +/- 10.7% versus 22.8 +/- 7.6%, P=.2). In either case, however, a single daily serving provided most of the iron and zinc requirements for the children. CONCLUSIONS: Single daily servings of multinutrient-fortified beverages can meet much of the mineral needs for small children. Food has a small inhibitory effect on iron, but not zinc, absorption; therefore, these beverages can be efficacious even when given with a meal.

A multinutrient-fortified beverage enhances the nutritional status of children in Botswana.

Due to their widespread acceptability, multinutrient-fortified foods and beverages may be useful in reducing micronutrient deficiencies, especially in developing countries. We studied the efficacy of a new fortified beverage in improving the nutritional status of children in Botswana. We screened 311 lower income urban school children, ages 6-11 y, in two primary schools near Gaborone. Children were given seven 240-mL servings weekly of either an experimental beverage (EXP) fortified with 12 micronutrients or an isoenergetic placebo drink (CON) for 8 wk. Weight, mid-upper arm circumference, hemoglobin, retinol, ferritin, vitamin B-12, folate and riboflavin status were measured at baseline and at the end of the study. Plasma zinc and serum transferrin receptors also were measured at study end. A total of 145 children in the EXP group and 118 in the CON group completed the trial. Using multivariate analysis, the changes in mid-upper arm circumference, weight for age and total weight were significantly better in the EXP group than in the CON group (P < 0.01). Ferritin, riboflavin and folate status were significantly better in the EXP group than in the CON group at study end (P < 0.01), but serum vitamin B-12 was not. Zinc was significantly higher and transferrin receptors were significantly lower at the conclusion of the study in the EXP group than in the CON group (P < 0.001). Mean plasma retinol concentrations, which were low (<0.7 micro mol/L) in both groups, did not change. We conclude that a micronutrient-fortified beverage may be beneficial as part of a comprehensive nutritional supplementation program in populations at risk for micronutrient deficiencies.

Cofortification of iron-fortified flour with zinc sulfate, but not zinc oxide, decreases iron absorption in Indonesian children.

BACKGROUND: Iron deficiency is a major nutritional concern in developing countries, and food fortification is a common strategy to treat it. In Indonesia wheat flour is fortified with 60 mg Fe/kg, but because of increasing concerns about marginal zinc status in at-risk populations, consideration is being given to cofortifying flour with zinc. However, little is known about the effect of zinc fortification of flour on iron bioavailability or about the optimum form of zinc supplementation. OBJECTIVE: We measured iron and zinc bioavailability from wheat-flour dumplings containing 25 g flour fortified with 60 mg Fe/kg, either alone or with 60 mg Zn/kg as zinc oxide or as zinc sulfate. DESIGN: Ninety children aged 4-8 y were recruited and assigned randomly to the 3 groups; 86 completed the study. Iron and zinc absorption were measured with established stable-isotope methods. RESULTS: Iron absorption from the flour fortified with iron only was good (15.9 +/- 6.8%), but when corrections were made for hemoglobin concentrations, it was significantly lower from the flour cofortified with zinc sulfate (11.5 +/- 4.9%; P < 0.05) but not from the flour cofortified with zinc oxide (14.0 +/- 8.9%). Zinc absorption was not significantly different between the zinc oxide and zinc sulfate cofortified flours (24.1 +/- 8.2% compared with 23.7 +/- 11.2%; P = 0.87). CONCLUSIONS: Iron and zinc appear to be highly bioavailable from foods made from fortified flour, but zinc sulfate cofortification may have a detrimental effect on iron absorption.