A new formula for blood transfusion volume in the critically ill

Background: Published formulae, frequently used to predict the volume of transfused red cells required to achieve a desired rise in haemoglobin (Hb) or haematocrit (Hct), do not appear to have been validated in clinical practice. Aims: To examine the relation between transfusion volume and the resulting rise in Hb and Hct in critically ill children. Methods: Phase 1: Sample of 50% of children admitted during 1997; 237 of these 495 patients received at least one packed red cell transfusion; 82 children were transfused without confounding factors that could influence the Hb/Hct response to transfusion and were analysed further. Actual rise in Hb concentration or haematocrit was compared to that expected from use of existing formulae. A new formula was developed. Phase 2: In 50 children receiving a packed red cell transfusion during 2001, actual rise in Hb concentration was compared to expected rise in Hb with use of the new formula. Results: Phase 1: Existing formulae performed poorly; median ratio of actual/predicted rise in Hb or Hct ranged from 0.61 to 0.85. Using the regression coefficients new formulae were developed for both Hb and Hct. These formulae were applicable across all age and diagnostic groups. Phase 2: Median ratio of actual/predicted rise in Hb improved to 0.95 with use of the new formula. Conclusions: Existing formulae underestimate the volume of packed red cells required to achieve a target Hb or Hct. Adoption of the new formulae could reduce the number of transfusion episodes in PICU, cutting costs and reducing risk.     

A new formula for blood transfusion volume in the critically ill.

BACKGROUND: Published formulae, frequently used to predict the volume of transfused red cells required to achieve a desired rise in haemoglobin (Hb) or haematocrit (Hct), do not appear to have been validated in clinical practice. AIMS: To examine the relation between transfusion volume and the resulting rise in Hb and Hct in critically ill children. METHODS: Phase 1: Sample of 50% of children admitted during 1997; 237 of these 495 patients received at least one packed red cell transfusion; 82 children were transfused without confounding factors that could influence the Hb/Hct response to transfusion and were analysed further. Actual rise in Hb concentration or haematocrit was compared to that expected from use of existing formulae. A new formula was developed. Phase 2: In 50 children receiving a packed red cell transfusion during 2001, actual rise in Hb concentration was compared to expected rise in Hb with use of the new formula. RESULTS: Phase 1: Existing formulae performed poorly; median ratio of actual/predicted rise in Hb or Hct ranged from 0.61 to 0.85. Using the regression coefficients new formulae were developed for both Hb and Hct. These formulae were applicable across all age and diagnostic groups. Phase 2: Median ratio of actual/predicted rise in Hb improved to 0.95 with use of the new formula. CONCLUSIONS: Existing formulae underestimate the volume of packed red cells required to achieve a target Hb or Hct. Adoption of the new formulae could reduce the number of transfusion episodes in PICU, cutting costs and reducing risk.     

ARA or no ARA in infant formulae,that is the question

Recently, the European Commission issued a Delegated Regulation updating the compositional and information requirements for infant and follow-on formulae that are to be applied at the latest in February 2021. This new regulation changes the status of docosahexaenoic acid (DHA) from an optional ingredient to a mandatory nutrient in these formulae at levels between 20 and 50 mg/100 kcal (0.5–1% of fatty acids). By contrast, arachidonic acid (ARA) becomes an optional nutrient. Following publication of the new regulation, global scientific experts have expressed concerns regarding the potential health risks of new infant formulae containing only DHA, especially at levels higher than those in breast milk and infant formulae marketed to date. Both DHA and ARA play a crucial role in infant development. First, breast milk, the gold standard for infant feeding, contains both DHA and ARA. Second, during development, the conversion of linoleic acid into ARA through desaturation steps is not sufficient to meet nutritional needs, especially in carriers of newly identified genetic variants in fatty acid desaturases, which weaken the biosynthetic production of ARA. Third, circulating levels of DHA and ARA in breastfed infants can only be matched with the addition of both fatty acids to formulae. And fourth, most studies performed to date have demonstrated that important physiological and developmental endpoints are sensitive to the ratio of dietary ARA:DHA. The precautionary principle applies when implementing the new EU regulation for infant and follow-on formulae. As a consequence, given the vulnerability of developing infants as well as the absence of conclusive evidence that formulae with at least 20 mg DHA/100 kcal, but no ARA, are safe and suitable to support the growth and development of infants similar to their breastfed peers, it remains necessary to still market formulas containing both ARA and DHA until proved otherwise.     

Curd and whey proteins in the nutrition of low birthweight babies.

Some animals thrive more satisfactorily on a milk that contains whey and curd protein. For this reason human milk protein (which contains about 40% whey) may have some advantages over cows'' milk protein (which contains about 15% whey) and so infants feeding formulae based on demineralised whey in which the protein has been modified to achieve a curd:whey ratio similar to that in human milk may also thrive more satisfactorily. As the exact situation in the human newborn is unclear, the effects of feeding a formula containing unmodified cows'' milk protein (mainly curd) and one containing the same amount of modified cows'' milk protein (curd and whey) were studied in 57 low birthweight babies during the first 3 months of life. During the early weeks of life the curd and whey group grew bigger, absorbed more nitrogen, and excreted proportionately less urea. These results suggest that a curd and whey formula has advantages in the protein nutrition of low birthweight babies, especially the preterm ones. We feel it would be unwise to reduce the protein content of a formula based on cows'' milk below 15 g/1 unless it was modified to achieve a larger proportion of whey protein and hence, among other qualities, more cysteine. Although some of the qualities of human milk protein can be mimicked by the use of demineralised whey formulae, others cannot.     

Soy protein infant formulae and follow-on formulae: a commentary by the ESPGHAN Committee on Nutrition

This comment by the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) Committee on Nutrition summarizes available information on the composition and use of soy protein formulae as substitutes for breastfeeding and cows' milk protein formulae as well as on their suitability and safety for supporting adequate growth and development in infants. Soy is a source of protein that is inferior to cows' milk, with a lower digestibility and bioavailability as well as a lower methionine content. For soy protein infant formulae, only protein isolates can be used, and minimum protein content required in the current European Union legislation is higher than that of cows' milk protein infant formulae (2.25 g/100 kcal vs. 1.8 g/100kcal). Soy protein formulae can be used for feeding term infants, but they have no nutritional advantage over cows' milk protein formulae and contain high concentrations of phytate, aluminum, and phytoestrogens (isoflavones), which might have untoward effects. There are no data to support the use of soy protein formulae in preterm infants. Indications for soy protein formulae include severe persistent lactose intolerance, galactosemia, and ethical considerations (e.g., vegan concepts). Soy protein formulae have no role in the prevention of allergic diseases and should not be used in infants with food allergy during the first 6 months of life. If soy protein formulae are considered for therapeutic use in food allergy after the age of 6 months because of their lower cost and better acceptance, tolerance to soy protein should first be established byclinical challenge. There is no evidence supporting the use of soy protein formulae for the prevention or management of infantile colic, regurgitation, or prolonged crying.     

Adhesion inhibitory activity of β-lactoglobulin isolated from infant formulae

β-Lactoglobulin was isolated from infant formulae that were ultra high temperature (UHT) -treated, sterilized or spray-dried. The effect of the isolated β-lactoglobulin on SfaII-fimbriae-mediated adhesion of Escherichia coli to human ileostomy glycoproteins was studied in vitro. β-Lactoglobulin isolated from sterilized formulae was found to perform significantly less well than preparations from spray-dried formulae (p = 0:05). Great heterogeneity was observed in the adhesion inhibitory capacity of β-lactoglobulin isolated from UHT-treated formulae. Therefore, no significant difference was observed between UHT-treated and sterilized formulae or spray-dried formulae (p < 0:10). It can be hypothesized that β-lactoglobulin from spray-dried and some UHT-treated infant formulae may affect the colonization of mucous membranes by E. coli strains causing neonatal septicaemia and meningitis.     

Induktion der oralen Toleranz bei Kindern mit Kuhmilchallergie

Cow's milk allergy (CMA) is the most frequent food allergy in early childhood, occurring during the first months of life. Despite its spontaneous benign evolution, CMA is still problematic, since diagnosis remains unsafe and the prediction of clinical outcome and time of appearance of oral tolerance (OT) is difficult. The acquisition of OT is of 45–56% at 1 year, 60–77% at2 years and about 90–95% after 5 to 10 years. The concept of OT is a mechanism of immunological regulation, which consists of a modulation of the systemic immune response to oral proteins. The main actors of OT are: antigens, digestive mucosal, antigen-presenting cells and T-lymphocytes. The most common food allergens are cow's milk, soy and egg proteins, as well as fish and seafood products and peanuts. Two types of oral tolerance exist: primary, which is the induction of tolerance to a formerly unknown antigen; and secondary, which is a re-induction of OT to an antigen. The role of eviction of antigens and of partially hydrolyzed formulae was largely studied for primary tolerance. For secondary OT, patients must receive a cow's milk-free diet and extensively hydrolyzed formulae until its spontaneous appearance, which, as shown in a recent study, seems to be quicker with the use of oligopeptides rather than amino acids.     

Adequacy of clinical formulae for estimation of energy requirements in children with cystic fibrosis.

BACKGROUND: Two clinical formulae (CF conference formula and estimation based on 120% of average requirement for energy) have been recommended for the estimation of energy requirements in cystic fibrosis but their accuracy is unknown. AIM: To compare the accuracy of estimates of energy requirement derived from the two formulae. METHODS: Energy requirement, defined as total daily energy expenditure, was measured using the doubly labelled water method in 15 patients (six girls, nine boys; mean (SD) age, 10.0 (2.4) years) who were well and clinically stable. The accuracy of the formulae was assessed using calculation of biases and limits of agreement relative to measured energy requirement. RESULTS: Estimates from the CF conference formula were lower than measured values (mean paired difference, 0.52 MJ/day; 95% confidence interval (CI), -1.10 to 0. 10), but this bias was not significant, and was smaller than that from the alternative formula (mean paired difference, 0.77 MJ/day; 95% CI, -0.20 to 1.74). Limits of agreement relative to measured total daily energy expenditure were narrower for the CF conference formula (-2.72 to 1.68 MJ/day) than for that based on 120% of estimated average requirement (-2.75 to 4.29 MJ/day), but with both formulae errors in estimation at the individual level were large. CONCLUSIONS: The CF conference formula offers improved prediction of energy requirements, but the accuracy of both formulae at the individual level is not sufficiently good for clinical purposes.     

In vivo and in vitro studies on the residual allergenicity of partially hydrolysed infant formulae

AIM: Because allergen-reduced formulae are widely used in the prevention and treatment of cow's milk allergy in children and because anaphylactic reactions have been reported for some hydrolysed formulae, it is of clinical relevance to know about the residual allergenicity of so-called hypoallergenic formulae. METHOD: We therefore studied the reactions of 20 children (mean age 1.6 years) with proven cow's milk allergy to a variety of formulae, using skin prick test, specific IgE in serum, protein content and RAST inhibition. RESULTS: Whereas all but two children with a clinically relevant cow's milk allergy had a positive skin prick test to cow's milk, some children still showed positive responses to the partially hydrolysed formulae. No child had a positive skin test to the amino acid formula. Specific IgE to the partially hydrolysed whey formula (median 0.28 U/ml) was significantly lower (p < 0.003) than to cow's milk. Specific IgE to the partially hydrolysed whey/casein formula, soy/pork collagen hydrolysate and the amino acid formula was in a low range (median values 0.19, 0.23 and 0.21 U/ml, respectively). While determination of the protein content of the formulae gave no valid information, RAST/EAST inhibition was highest for cow's milk, followed by the partially hydrolysed whey formula, partially hydrolysed whey/casein formula, soy/pork collagen formula, and the amino acid formula. CONCLUSION: Skin prick test and RAST inhibition test are suitable methods for determining the residual allergenicity of hydrolysed infant formulae, while determination of protein content using the applied modified Lowry method is not helpful.     

Taste preferences and feeding behaviour in children with phenylketonuria on a semisynthetic diet

Low-phenylalanine formula for phenylketonuria (PKU) made from free amino acids as a protein source (AAM formula) has a poor taste and smell. We developed a more palatable formula using low-phenylalanine peptide (LPP) as a protein source. Palatability tests performed by 41 healthy adults confirmed that the palatability of LPP formula was significantly better than that of AAM formula. A group of 48 patients with PKU who had been administered AAM formula since the newborn period were assessed for their preference between the AAM and LPP formulae and their feeding behaviour was compared to that in healthy children. Of patients, 90.9% and 66.6% of healthy infants less than 18 months of age took both formulae without apparent preference, suggesting that sensitivity to taste and smell is more immature in infancy than in later life. Of patients with PKU aged between 18 months and 11 years, 29.1% liked AAM formula rather than the LPP formula, while 66.7% took both formulae without apparent preference. Most healthy children in the same age group who had never previously tasted therapeutic formulae disliked it, although they tended to prefer the LPP formula. Of patients aged between 11 and 17 years, 84.6% preferred the LPP formula while 15.4% preferred the AAM formula. In the controls of this age group, 33% disliked therapeutic formulae, but they tended to prefer the LPP formula. Conclusion In some young children with phenylketonuria the characteristic taste of amino acid mixture formula encountered in early life is considered to be imprinted and remains as a preference for a long time. Since school children with phenylketonuria usually obtain about 50% of their energy intake from natural food containing small amounts of protein, these patients are considered to have come to have similar preferences as healthy people which result from a waning of the imprinted taste of amino acid mixture formula. Received: 15 February 2000 / Accepted: 15 May 2000     

Questions to the supply of young infants with fat and fatty acids

The fat content and the fatty acid pattern were analyzed in 30 commercially prepared milk formulae for healthy infants in the first 6 months of life.We found an average fat content of 3.4 g or 3.6 g/100 ml in partly adapted and adapted milk formulae, between 1.4 g and 3.3 g/100 ml in not defined milk formulae. We regard a fat content lower than 3.0 g/100 ml and more than 4.0 g/100 ml as not advisable.In most milk formulae the ratio of saturated: unsaturated fatty acids is similar to the ratio in human milk fat. This ratio is obtained from a mixture of cow's milk fat with vegetable oils or by a mixture of various vegetable fats.The differences in the fatty acid pattern between the milk formulae and the fatty acid pattern in mature human milk are demonstrated and discussed.The tolerance of milk formulae for young infants is not influenced in an unfavorable manner by butyric acid. A high portion of lauric acid in milk formulae seems undesirable.The importance of the position of palmitic acid in the triglycerides of milk formulae for infants is discussed, and it is referred to the advantage of a mixture of cow's milk fat with vegetable fats.A linoleic acid content of 3 kcal% in the minimum and 7 kcal% in the maximum in milk formulae for infants is regarded as advisable.The investigations were supported by the Ministerium für Wissenschaft und Forschung des Landes Nordrhein-Westfalen, Federal Republic of Germany.     

Betaine and homocysteine concentrations in infant formulae and breast milk

BACKGROUND: Early diagnosis and treatment of homocystinuria with methionine-free or low methionine formulae significantly improve prognosis in children found by newborn screening and treated soon after birth. Betaine (Bet) supplementation is also an effective strategy for dietary treatment of homocystinuria. However, previous reports on diet therapy have only examined methionine and cysteine concentrations but not those of Bet and homocysteine (Hcy) in infant diets. METHODS: We measured Bet and Hcy concentrations in three methionine-free formulae, five infant starter formulae, and 33 samples of human breast milk from 10 mothers. RESULTS: In methionine-free formulae, Hcy but not Bet was isolated. However, in human breast milk and infant starter formulae, both Bet and Hcy were detected. However, the Bet concentration was not sufficient for the treatment. CONCLUSIONS: Our study suggests that methionine-free formulae should have Hcy eliminated and be fortified with Bet to the concentration of 150 mg/dL for the treatment of homocystinuria.     

The significance of iron in development and nutrition of infants. II. Prevention of iron deficiency

The symptoms and consequences of iron deficiency in the child are described as found in the literature. The role of iron in immune processes is presented and it is noted that there is no proof for the theory of the development of bacterial infections as a result of giving oral iron supplements. The influence of breast milk and cow milk on the intestinal uptake and loss of iron is discussed. Feeding infants formulae or milk-substitute formulae after cessation of breastfeeding prevents the increased blood loss in the digestive tract, which results from the introduction of cow's milk. The iron content of selected Polish infant formulae, follow-on formulae and milk-substitute formulae available on the market are given and compared with FAO, WHO, ESPGAN and EC recommendations. Results of the authors' own researches on the iron content of selected Polish powdered whole cow's milks are presented. The measurements, made by atomic absorption spectroscopy (AAS), showed that iron content of whole powdered milks ranged from 0.23 to 1.19 mg/dm3. The values do not vary significantly from those in the literature on the iron content of unboiled cow's milk. It is shown that up to the point of the doubling of birth weight, formula-fed infants should be fed modified milk containing at least 2 mg/dm3 of iron. Thereafter infants should receive milk containing at least 7 mg/dm3 of iron.     

Characterization of antigens and allergens in hypo-allergenic infant formulae

The antigenicity and allergenicity of so-called hypo-allergenic infant formulae is mainly determined by the degree of hydrolysis and ultrafiltration. Five different formulae were investigated by means of immunoblotting and RAST in order to characterize the antigens and allergens regarding their molecular weights, molecular origin and their ability to bind human IgG and IgE antibodies: A non hydrolysed infant formula (I-F), a mixture of the major cow's milk proteins (PM), a whey-based infant formula (W-H), a whey-based and ultra-filtrated infant formula (U-H), a casein/whey-based infant formula (CW-H). By immunoblotting we demonstrated that all tested formulae still contain antigens with molecular weights from 3 to 67 kD. But when compared with I-F and PM the antigen content of the hydrolysed formulae was considerably lower. The lowest antigen content could be demonstrated in U-H, which contains casein fragments (3–6 kD) and beta-lactoglobulin and its fragments (6–18 kD). W-H and CW-H contain bovine serum albumin, beta-lactoglobulin, casein and their fragments (3–67 kD). All hydrolysed formulae tested showed a reduced IgE-binding capacity. Three out of 12 cow's milk allergic children possessed IgE binding to U-H or W-H, and 5 of them IgE against CW-H.Conclusion The enzymatic hydrolysis plus ultra-filtration seems to be the most efficient method to reduce the antigen content of so-called hypo-allergenic infant formuale.     

Allergenicity of milk protein hydrolysate formulae in children with cow's milk allergy

Cow's milk protein hydrolysate formulae have been developed to lower or eliminate the allergenicity of cow's milk proteins, and to reduce the antigenic load and the risk of sensitization. Cross-reactivity between different hydrolysate formulae and cow's milk proteins has been demonstrated. We have studied 20 children (median age 31 months, range 15–76 months) with a history of IgE-mediated cow's milk allergy. All the children had immediate allergic respiratory and/or cutaneous and/or gastro-intestinal reactions to cow's milk ingestion. In addition, the children had positive prick skin tests and positive RAST to cow's milk. Prick skin test, RAST, and double-blind placebo controlled food challenges were performed with three different hydrolysate formulae: a casein hydrolysate formula and two whey formulae, one partially and one extensively hydrolyzed. All 20 children had immediate allergic reactions after the challenge test with cow's milk. Only 2/20 children had a positive challenge test with a casein hydrolysate formula (Alimentum): one developed asthma and one urticaria. Two of the 15 children challenged with an extensively hydrolysed whey formula (Profylac) developed perioral erythema. Nine out of 20 children had a positive challenge test with a partially hydrolysed whey formula (Nidina H.A.): four developed asthma, three urticaria and two lip oedema. All children had positive prick skin tests to cow's milk proteins (casein and/or lactalbumin); 9 to Nidina H.A.; 3 to Profylac, and 3 to Alimentum. Specific IgE antibodies to cow's milk were present in all children; in 13 to Nidina H.A., in 4 to Profylac, and in 3 to Alimentum.     

Polyunsaturated fatty acids in infant nutrition

The availability of long-chain polyunsaturated fatty acids (LCP), such as arachidonic (C20:4n-6) and docosahexaenoic (C22:6n-3) acids, is important for early human growth and development. The capacity for endogenous synthesis of LCP from the precursor fatty acids lineoleic (C18:2n-6) and alpha-linolenic (C18:3n-3) acid is limited in preterm and probably also in term infants. In utero, LCPs seem to be transferred preferentially from the mother to the foetus by the placenta. After birth, breastfed infants receive preformed dietary LCP with human milk. In contrast, most current infant formulae are devoid of LCP. Premature infants fed such formulae develop rapid LCP depletion of plasma and tissue lipids, which is associated with reduced visual acuity during the first postnatal months. Therefore, LCP enrichment of formulae for premature infants is desirable. Recent observations indicate that term infants fed conventional formulae also exhibit lower plasma LCP values and may show functional disadvantages, but these data require further confirmation prior to drawing definite conclusions.     

Clinical manifestations of allergy related to breast and cows' milk feeding.

The frequency of allergic manifestations in the first year of life was studied. The prevalence of allergic signs affecting the skin and respiratory tract in infants who had been started on breast feeding was compared with the prevalence of such signs in infants started on cows'' milk formulae. The relationship of allergy to family history was investigated. Eczema and rhinitis were found to be present as often in the initially breast-fed group as in the initially cows'' milk-fed group. Bottle-fed infants developed asthma and bronchitis more often than their breast-fed counterparts. Infants of allergic parents exhibited more allergy than those from non-allergic families, and this difference was particularly pronounced for asthma or bronchitis. Breast feeding gave some protection against the development of respiratory tract allergies in infants of non-allergic parents. Among the infants with a positive family history of allergy, fewer with eczema or chronic rhinitis were found in the initially breast-fed group group but this did not achieve statistical significance.     

INFANT FORMULA

Mettler, A. E. (Farley Health Products Limited). Infant formula. Acta Paediatr Scand, Suppl. 299:58, 1982.—The modern infant formula has been evolved over many generations and major changes have taken place in the U.K. even in the last ten years to produce formulae which are predominantly of the low solute type. Modifications of scoop design and method of reconstitution, together with formulae changes, appear to have reduced considerably the problems associated with old type cows'whole milk formulae. From examination of nutritional guidelines and legislation available worldwide for infant formula, it is proposed that modifications of these guidelines are required especially with those proposed by Codex Alimentarius. Although it would seem sensible that mature breast milk analysis be used as a model for infant formula such a route may not give any improvement in the nutritional quality of milks currently available. Indeed perfect imitation of breast milk by artificial means is most unlikely. Possible areas for future research are briefly discussed.     

CHANGING PATTERN OF COW'S MILK INTOLERANCE: An Analysis of the Occurrence and Clinical Course in the 60s and mid-70s

ABSTRACT. Verkasalo, M., Kuitunen, P., Savilahti, E. and Tiilikainen, A. (Children's Hospital, University of Helsinki, Finland). Changing pattern of cow's milk intolerance. Acta Paediatr Scand, 70: 289, 1981.–The rapid changeover to commercial adapted infant formulae which took place in Finland between 1973 and 1975 was studied as a factor in the occurrence of severe intestinal cow's milk intolerance (CMI). Of infants treated for CMI in 1962-73, ninety-three percent (25/27) were on homemade or unadapted formulae. The admission rate for CMI in these years was 0.22/1 000 liveborn infants breast fed less than six months. During 1974-77 the corresponding figure was 0.56, with 85 % of the patients (18/26) on adapted cow's milk formulae. The patients treated before 1974 had a longer symptomatic period before admission, greater growth retardation and more severe intestinal damage than those seen during and after 1974. This is believed to reflect mainly the increasing awareness of CMI on the part of both laymen and the medical profession. In the history of 2/3 of the patients at least one of the following conditions was noted: non-breast feeding, infectious gastroenteritis, praematurity, 21-trisomy, prior intra-abdominal surgery, Hirschsprung's disease, and atopic disease in family members. The long follow-up averaging over four years revealed four patients with coeliac disease. In one of these the proximal jejunal mucosa was normal after two years on gluten-containing diet, but he showed a mucosal relapse as late as between 2 to 4 years on normal diet.