Randomized comparison of a nutrient-dense formula with an energy-supplemented formula for infants with faltering growth.

INTRODUCTION: The practice of supplementing standard infant formula with energy for infants with faltering growth has been widespread. This increases energy density but disturbs the protein : energy ratio, and increases risks of microbial contamination and errors in feed preparation. This study aimed to compare the effectiveness of a nutrient-dense formula (NDF) with an energy-supplemented formula (ESF) in infants with faltering growth. METHODS: In an open, parallel, randomized study, 49 infants with faltering growth were randomized to receive a NDF (4.2 kJ mL(-1)) or an ESF (4.2 kJ mL(-1)), for 6 weeks. Anthropometry, biochemistry, feed intake, stool and vomit frequency were collected. RESULTS: No significant differences in tolerance, feed volumes or energy intakes were recorded but the NDF group received 42% more protein and 15-40% more vitamins and minerals. Blood urea concentration in the ESF group fell by 50% over the trial period, suggesting a suboptimal protein : energy ratio in the ESF feed. The NDF group retained a normal mean blood urea concentration, a higher urinary potassium concentration and did not have the significant fall in length z-score seen in the ESF group. CONCLUSION: Increasing the energy content of normal infant formula without also increasing protein and micronutrients should not be practiced in infants with faltering growth.

Protein substitute dosage in PKU: how much do young patients need?

BACKGROUND: The optimal dose of protein substitute has not been determined in children with phenylketonuria (PKU). AIM: To determine if a lower dose of protein substitute could achieve the same or better degree of blood phenylalanine control when compared to the dosage recommended by the UK MRC.(1) METHODS: In a six week randomised, crossover study, two doses of protein substitute (Protocol A: 2 g/kg/day of protein equivalent; Protocol B: 1.2 g/kg/day protein equivalent) were compared in 25 children with well controlled PKU aged 2-10 years (median 6 years). Each dose of protein substitute was taken for 14 days, with a 14 day washout period in between. Twice daily blood samples (fasting pre-breakfast and evening, at standard times) for plasma phenylalanine were taken on day 8-14 of each protocol. The median usual dose of protein substitute was 2.2 g/kg/day (range 1.5-3.1 g/kg/day). RESULTS: When compared with control values, median plasma phenylalanine on the low dose of protein substitute increased at pre-breakfast by 301 mumol/l (95% CI 215 to 386) and in the evening by 337 micromol/l (95% CI 248 to 431). On the high dose of protein substitute, plasma phenylalanine concentrations remained unchanged when compared to control values. However, wide variability was seen between subjects. CONCLUSIONS: A higher dosage of protein substitute appeared to contribute to lower blood phenylalanine concentrations in PKU, but it did have a variable and individual impact and may have been influenced by the carbohydrate (+/- fat) content of the protein substitute.

Are tablets a practical source of protein substitute in phenylketonuria?

BACKGROUND: A phenylalanine-free amino acid based protein substitute is necessary to provide the major source of protein in phenylketonuria (PKU). Protein substitutes in PKU are usually given as drinks. These are unpalatable and compliance is often poor. Tablets containing a suitable mixture of phenylalanine-free amino acids (Aminogran Food Supplement, UCB) are now available. AIMS: To compare the effectiveness and acceptability of these tablets with conventional protein substitute drinks. METHODS: Twenty one subjects with PKU, aged 8-25 years, participated in a randomised crossover study. During one phase, subjects received at least 40% of their protein substitute requirements from the amino acid tablets and the rest from their usual protein substitute tablets. During the other phase, they received their usual protein substitute. Each period lasted 12 weeks. Blood phenylalanine concentrations were measured at least once every two weeks and other plasma amino acids were measured at the beginning, at crossover, and at the end of the study. The subjects kept a diary of all protein substitute taken. RESULTS: Compliance appeared to be better with the new tablets than with patients' usual protein substitutes. Ninety per cent (18/20) recorded that they took the tablets as prescribed, compared with 65% (13/20) fully compliant with their usual protein substitute. Moreover, plasma phenyalanine was lower on the amino acid tablets, and the median difference in blood concentrations between the two groups was 46 micro mol/l (95% CI 14.8 to 89.0, p = 0.02). Tyrosine increased by a median of 16 micro mol/l daily on the amino acid tablets (95% CI 7.1 to 40.5, p = 0.01). Most subjects (70%) preferred incorporating the new tablets into their usual protein substitute regimen. CONCLUSIONS: Amino acid tablets are an effective and relatively popular protein substitute in older children, teenagers, and adults with PKU.

Iron supplemented formula milk related to reduction in psychomotor decline in infants from inner city areas: randomised study.

OBJECTIVE: To compare the effect of unmodified cows' milk and iron supplemented formula milk on psychomotor development in infants from inner city areas when used as the main milk source. DESIGN: Double blind, randomised intervention trial. SETTING: Birmingham health centre. SUBJECTS: 100 infants, mean age 7.8 months (range 5.7 to 8.6 months), whose mothers had already elected to use unmodified cows' milk as their infant's milk source. INTERVENTION: Changing to an iron supplemented formula milk from enrolment to 18 months of age, or continuing with unmodified cows' milk. MAIN OUTCOME MEASURES: Developmental assessments using Griffiths scales at enrolment and at 18 and 24 months. RESULTS: 85 participants completed the trial. There were no significant differences in haemoglobin concentration between the two groups at enrolment, but by 18 months of age 33% of the unmodified cows' milk group, but only 2% of the iron supplemented group, were anaemic (P<0.001). The experimental groups had Griffiths general quotient scores that were not significantly different at enrolment, but the scores in both groups declined during the study. By 24 months the decrease in the mean scores in the unmodified cows' milk group was 14.7 whereas the decrease in the mean scores in the iron supplemented group was 9.3 (P<0.02, 95% confidence interval 0.4 to 10.4). Mean subquotient scores were considerably lower in the unmodified cows' milk group at 24 months; significantly so for personal and social scores (P<0.02, 1.2 to 16.8 [corrected]). CONCLUSION: Replacing unmodified cows' milk with an iron supplemented formula milk up to 18 months of age in infants from inner city areas prevents iron deficiency anaemia and reduces the decline in psychomotor development seen in such infants from the second half of the first year.

Enteral nutrition after bone marrow transplantation.

Nutritional insult after bone marrow transplantation (BMT) is complex and its nutritional management challenging. Enteral nutrition is cheaper and easier to provide than parenteral nutrition, but its tolerance and effectiveness in reversing nutritional depletion after BMT is poorly defined. Nutritional status, wellbeing, and nutritional biochemistry were prospectively assessed in 21 children (mean age 7.5 years; 14 boys) who received nasogastric feeding after BMT (mean duration 17 days) and in eight children (mean age 8 years, four boys) who refused enteral nutrition and who received dietetic advice only. Enteral nutrition was stopped prematurely in eight patients. Greater changes in weight and mid upper arm circumference were observed in the enteral nutrition group, while positive correlations were found between the duration of feeds and increase in weight and in mid upper arm circumference. Vomiting and diarrhoea had a similar incidence in the two groups, while fever and positive blood cultures occurred more frequently in the dietetic advice group. Diarrhoea occurring during enteral nutrition was not associated with fat malabsorption, while carbohydrate malabsorption was associated with rotavirus infection only. Enteral feeding did not, however, affect bone marrow recovery, hospital stay, general wellbeing, or serum albumin concentrations. Hypomagnesaemia, hypophosphataemia, zinc and selenium deficiency were common in both groups. In conclusion, enteral nutrition, when tolerated, is effective in limiting nutritional insult after BMT. With existing regimens nutritional biochemistry should be closely monitored in order to provide supplements when required.

Prevention of anaemia in inner city toddlers by an iron supplemented cows' milk formula.

There are few data to support the use of follow-on formulas in infants from the age of 6 months. In a prospective trial in a deprived inner city area of Birmingham 100 infants who were already receiving pasteurised cows' milk by 6 months of age were enrolled and randomised either to receive a follow-on formula or to continue on cows' milk from 6 months until 18 months. At 18 months of age the follow-on formula group returned to cows' milk and both groups were followed up until 24 months. Iron status, growth, and nutritional status were analysed at intervals of six months. At enrollment, no differences in haematological status were evident. However, by 12 months of age, 31% of the cows' milk group were anaemic (haemoglobin concentration < 110 g/l) compared with only 3% of those receiving follow-on formulas. At 18 months, 33% of the cows' milk group were anaemic compared with only 2% of the follow-on formula group and by 24 months of age none of the follow-on formula group was anaemic, whereas 26% in the cows' milk group still had a haemoglobin of < 110 g/l. Mean corpuscular volume was significantly smaller and ferritin significantly lower in the cows' milk group at 12, 18, and 24 months. Dietary iron intake was higher in the follow-on formula group at 12 and 18 months but not at 24 months, when both groups were back on cows' milk. Infants and toddlers at high risk of iron deficiency are therefore unlikely to become anaemic if receiving a follow-on formula, although the relative merits of follow-on formula compared with an ordinary infant formula remain uncertain.

Diagnosis and clinical associations of zinc depletion following bone marrow transplantation.

Following the emergence of biochemical zinc deficiency after bone marrow transplantation, the clinical value of plasma alkaline phosphatase activity as an early indicator of biochemical zinc depletion was investigated in this group of patients. Serial measurements of plasma zinc and alkaline phosphatase activities in 28 consecutive children (median age 8.7 years; 16 males) undergoing bone marrow transplantation were carried out and clinical associations recorded. A significant fall in plasma zinc occurred after the bone marrow transplant, and 19 children developed biochemical zinc deficiency (Zn < 11 mumol/l) at a median of 7 days following the transplant. Zinc depletion was more common in younger patients and in children with diarrhoea. A positive correlation was found between plasma zinc and alkaline phosphatase activities. Zinc depleted patients had more febrile episodes of longer duration and were more likely to have a positive blood culture. Haemopoetic recovery was not affected by zinc deficiency. Following zinc supplementation, alkaline phosphatase showed a significant increase. The sensitivity of a low alkaline phosphatase as a screening test for biochemical zinc deficiency was 83%, with a specificity of 86%. Low alkaline phosphatase activity following bone marrow transplant is an indication for zinc supplements.

Enteral nutrition as primary therapy in short bowel syndrome.

The spectacular success of parenteral nutrition in supporting patients during small intestinal adaptation after massive resection, tends to obscure the prolonged periods often needed for such adaptation to take place. After neonatal small intestinal resection for example, it may take more than five years before adaptation is complete. There is therefore a strong argument for examining ways in which adaptation can be facilitated, in particular, by the addition of novel substrates to enteral feeds. Pectin is completely fermented by colonic bacteria to short chain fatty acids. In the rat, addition of pectin to enteral feeds led to a more rapid adaptive response in both the small and large intestine after massive small intestinal resection, although faecal nitrogen losses were increased. In a similar rat model, the provision of 40% of non-protein energy as short chain triglycerides facilitated the adaptive response in the jejunum, colon, and pancreas. The importance of glutamine as a metabolic substrate for the small intestine makes it another potential candidate and some, but not all animal studies, have suggested a therapeutic effect: increasing the glutamine content of feeds to 25% of total amino acids produced enhanced jejunal and ileal hyperplasia, even on a hypocaloric feed, and an improved overall weight gain. Studies in humans are very limited, but such promising results in the experimental animal suggest that this is probably a fruitful area for further study.

Congenital sodium diarrhea with a partial defect in jejunal brush border membrane sodium transport, normal rectal transport, and resolving diarrhea.

Defective jejunal sodium/proton exchange causes severe, congenital secretory diarrhea. We report a boy who presented typically in utero, but in whom diarrhea resolved during the first year of life. Pregnancy was complicated by polyhydramnios, and an ultrasound at 31 weeks showed a distended fetal small intestine. The abdomen was grossly distended at birth, and profuse secretory diarrhea began immediately. He subsequently thrived on breast milk and electrolyte supplements. Studies of jejunal brush border sodium/proton exchange at 6 months showed a partial defect. Nonequilibrium rectal dialysis showed rectal sodium and potassium transport to be intact. Diarrhea lessened after 9 months, and the patient subsequently required occasional laxatives. These observations suggest that there is a spectrum of congenital abnormality in this exchanger, and that in children with incomplete defects normal colonic sodium salvage can subsequently mask net small intestinal secretion.

The effects of a pectin-supplemented elemental diet in a boy with short gut syndrome.

The effect of a pectin-supplemented diet in short gut syndrome was investigated in a 3-year-old boy. Nitrogen absorption was higher and stomach-to-anus transit time was prolonged during pectin supplementation of the enteral feed. Pectin supplementation had no adverse effects on electrolyte balance or glucose absorption. These data indicate that pectin supplementation of enteral feed may enhance nitrogen absorption and seems not to adversely affect absorption in short gut syndrome.

Egg and breast milk based nitrogen sources compared.

A nitrogen source based on egg protein (Vamin 9 glucose) and an alternative with an amino acid profile more similar to breast milk (Vaminolact), were compared in 14 parenterally fed infants. Subjects were randomly allocated to receive one or other amino acid solution, but were otherwise given identical diets. At the start of the study the two groups did not differ significantly in postconceptual age, postnatal age, or weight. Over a six day study period on a stable intake of intravenous nutrients there was no significant difference in growth or nitrogen retention between the two groups. Plasma amino acid profiles in those receiving Vamin 9 glucose, however, were frequently abnormal. Notably, mean concentrations of potentially neurotoxic phenylalanine and tyrosine were significantly higher (140% and 420%, respectively) in patients fed Vamin 9 compared with those given Vaminolact. An amino acid solution based on the composition of breast milk protein therefore brings plasma amino acid profiles during parenteral nutrition closer to those found in breast fed infants, and reduces in particular, the risks of hyperphenylalaninaemia and hypertyrosinaemia.