Comparison of an elemental with a hydrolysed whey formula in intolerance to cows' milk

In a double blind study, 40 infants with cows' milk intolerance of various causes were randomised to receive a nutritionally complete formula in which nitrogen was supplied either as whey hydrolysate or amino acids. The median age of infants was 10 weeks (range 36 weeks' gestation to 108 weeks' postnatal age). After a median follow up period of 25 weeks there was no significant difference in dietary intake between the formulas. Twenty four weeks after entry, weight and weight for length improved equally on both formulas. Plasma albumin improved significantly on the hydrolysed whey formula but not in the amino acid group. Both milks were palatable and normal intakes of formula were maintained. Biochemical and haematological indices remained within normal limits. There was no difference in stool frequency and vomiting between the two formulas. Two infants developed a probable allergic colitis while receiving hydrolysed whey. Amino acid formula may have a role in the management of atopic infants with severe cows' milk intolerance who have already reacted to whey or casein hydrolysate formula.     

Comparison of an elemental with a hydrolysed whey formula in intolerance to cows' milk.

In a double blind study, 40 infants with cows'' milk intolerance of various causes were randomised to receive a nutritionally complete formula in which nitrogen was supplied either as whey hydrolysate or amino acids. The median age of infants was 10 weeks (range 36 weeks'' gestation to 108 weeks'' postnatal age). After a median follow up period of 25 weeks there was no significant difference in dietary intake between the formulas. Twenty four weeks after entry, weight and weight for length improved equally on both formulas. Plasma albumin improved significantly on the hydrolysed whey formula but not in the amino acid group. Both milks were palatable and normal intakes of formula were maintained. Biochemical and haematological indices remained within normal limits. There was no difference in stool frequency and vomiting between the two formulas. Two infants developed a probable allergic colitis while receiving hydrolysed whey. Amino acid formula may have a role in the management of atopic infants with severe cows'' milk intolerance who have already reacted to whey or casein hydrolysate formula.     

Preventive effect of feeding high-risk infants a casein hydrolysate formula or an ultrafiltrated whey hydrolysate formula. A prospective, randomized, comparative clinical study

In a prospective study of a 1-year birth cohort of 158 high-risk infants the effect of feeding breastmilk, a casein hydrolysate (Nutramigen®) or a new ultrafiltrated whey hydrolysate (Profylac®) on the development of cow milk protein allergy/intolerance (CMPA/CMPI) was assessed and compared. All the infants had biparental or severe single atopic predisposition, the latter combined with cord blood IgE ≥ 0. 5 kU/L. At birth all infants were randomized to Nutramigen or Profylac, which was used when breastfeeding was insufficient or not possible during the first 6 months of life. During the same period this regimen was combined with avoidance of solid foods and cow milk protein. All mothers had unrestricted diets and were encouraged to do breastfeeding only. Moreover, avoidance of daily exposure to tobacco smoking, furred pets and dust-collecting materials in the the bedroom was advised. The infants were followed prospectively from birth to 18 months of age. All possible atopic symptoms were registered and controlled elimination/challenge studies were performed when symptoms suggested CMPA/CMPI. A total of 154 (97%) were followed up and 141 followed the diet strictly. Eighty-eight (62%) of the infants were breastfed for at least 6 months, 20 (14%) were breastfed exclusively, 59 and 62 had varying amounts of Nutramigen or Profylac respectively. CMPA/CMPI was diagnosed in 1/20, 1/59 and 3/62 in the breastfed, the Nutramigen and Profylac groups respectively, but 1 of the latter also had Nutramigen. None of the infants showed reactions against Nutramigen or Profylac. In 4 infants symptoms were provoked by breastmilk when the mother ingested cow milk and in 1 only by cow milk. The incidence of CMPA/CMPI among the infants who followed the dietary prevention programme was 3. 6% (5/141) which was a significant reduction compared to 20% (15/75) in an identically defined high-risk group without dietary preventive measures. None of the infants in the prevention group developed CMPA/CMPI after the age of 6 months. We conclude that feeding breastmilk, an extensively hydrolysed casein formula (Nutramigen) or an ultrafiltrated whey hydrolysate (Profylac) combined with avoidance of solid foods during the first 6 months of life in high-risk infants significantly reduced the cumulative incidence of CMPA/CMPI during the first 18 months of life. No difference was noted whether the infants were fed breastmilk, Nutramigen or Profylac and a diet period of 6 months seems sufficient. Both formulae were well tolerated and accepted by the infants.     

Safety of a new, ultrafiltrated whey hydrolysate formula in children with cow milk allergy: a clinical investigation

The purpose of this study was to determine whether a new ultrafiltrated whey hydrolysate infant formula, Profylac®, could be administered safely to children with cow milk protein allergy/intolerance. Profylac has a stated molecular weight of < 8 kD and at least 30, 000 times reduced antigenicity which is controlled by a combination of ELISA-techniques and immunochemical methods. The study comprised 66 children with cow milk protein allergy/intolerance diagnosed by controlled elimination/ challenge procedures. The children were aged 1 month-14. 5 years, median 1% years and 15 were below 1 year. Thirty-five of these children had proven IgE-mediated reactions (cow milk protein allergy). Sixty-one of the children had at least two different symptoms and 31 had concomitant allergies to other foods and/or inhalants. All 66 children underwent and tolerated open, controlled challenges with Profylac. A total of 64 children continued having Profylac daily for at least 3 months and 58 for at least 6 months after challenge. Nine of the children older than 1 year did not like the taste and only had Profylac in minor amounts. No side effects were registered. Fifteen of the infants were below 1 year of age, and this group was compared with an age matched group of 16 infants challenged with and fed an extensively hydrolysed casein hydrolysate, Nutramigen®. All the infants in these two groups accepted and tolerated Profylac and Nutramigen, respectively, and no side effects were registered. Among the 35 patients with IgE-mediated reactions 6% (2/35) had positive skin prick tests and 11% (3/28) had specific IgE class 2 against Profylac, 2 of the latter before intake of Profylac. None of the patients with non-IgE-mediated reactions had a positive skin prick test or specific IgE against Profylac. The study provides 95% confidence that this product is tolerated by at least 95% of children with cow milk protein allergy/intolerance and by 90% with IgE-mediated reactions. We conclude, that this ultrafiltrated whey hydrolysate is generally safe to feed to children with verified adverse reactions to cow milk protein, including children with IgE-mediated reactions. The taste of the product was widely accepted, also by older children.     

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.     

L'allergie aux hydrolysats de protéines du lait de vache. À propos de huit cas

BACKGROUND: The use of extensively hydrolyzed protein formulas is the best alternative for children with cow's milk allergy, though cases of allergies to hydrolyzed proteins have been reported. The aim of this study was to clarify from our experience the diagnostic, evolutive and therapeutic aspects of allergies to extensively hydrolyzed protein formulas. PATIENTS AND METHODS: We report eight cases of allergy to extensively hydrolyzed protein formulas seen between 1985 and 1998. The diagnostic criteria for allergy were either the appearance of immediate anaphylactic reactions after the ingestion of protein hydrolysate or a positive challenge test with the protein hydrolysate. RESULTS: Four children developed immediate anaphylactic symptoms after ingesting protein hydrolysate, and four children demonstrated subacute or chronic gastrointestinal symptoms. All children who developed acute anaphylactic symptoms had positive skin tests and specific IgF, antibodies (RAST) to cow's milk and/or hydrolyzed proteins. Conversely, in the four children with chronic gastrointestinal symptoms, skin tests and specific IgE antibodies were negative in three cases, but intestinal histology was abnormal in all of them when they were fed with a protein hydrolysate; this became normal after excluding the hydrolysate (data available in only two cases). Three children tolerated another protein hydrolysate form (whey vs. casein), four children had a favourable outcome when fed with human milk, and an amino-acid-based formula was successfully used in the most recent case. Nonhydrolyzed cow's milk proteins were tolerated after the age of 18 months in six children. Other atopic symptoms were observed in six children. CONCLUSION: Allergy to cow's milk protein hydrolysate is rare. The diagnosis is usually easy in children who develop acute anaphylactic symptoms, though intestinal histology is generally necessary for the diagnosis of allergy with chronic gastrointestinal symptoms. Treatment is based on the use of either another protein hydrolysate form (whey vs. casein) or an amino-acid-based formula.     

Calcium and zinc retention from protein hydrolysate formulas in suckling rhesus monkeys.

OBJECTIVE--To determine calcium and zinc retention from infant formulas based on protein hydrolysates. DESIGN--Randomized, crossover. SETTING--Newborn nursery at the California Primate Research Center, Davis. PARTICIPANTS--Suckling infant rhesus monkeys (N = 7), aged 6 weeks at the beginning of the study. Each infant received seven different formulas. INTERVENTIONS--Fasted infant monkeys were fed diets radiolabeled with calcium 47 and zinc 65. Retention was determined by counting whole body radioactivity immediately after dosing and 7 days after dosing. MEASUREMENTS AND RESULTS--Retention of 47Ca was a mean (+/- SEM) of 79% +/- 4% from casein hydrolysate and 72% +/- 6% from the whey protein hydrolysate formula. Calcium 47 retention from hydrolysates based on whey protein/casein mixtures (a ratio of 60:40 or 50:50) was similar despite differences in protein sources and calcium content. Calcium 47 retention from two types of soy/collagen hydrolysate formula was found to be 68% +/- 6% and 59% +/- 4%, respectively, which is significantly lower than retention from casein hydrolysate. Considering the different calcium content of these formulas, total calcium retention from milk protein hydrolysates was higher than from soy/collagen products. Retention of 65Zn from milk protein hydrolysates ranged from 18% +/- 3% to 29% +/- 4% and was higher than that from soy/collagen formulas with a mean retention of 7% +/- 3% and 10% +/- 4%, respectively. Despite these differences in 65Zn retention, total zinc retention from all soy/collagen formulas was similar due to their higher zinc content. CONCLUSIONS--Calcium and zinc bioavailability was high from formulas based on milk protein hydrolysate, but was considerably lower from soy hydrolysates. Higher levels of calcium and zinc provided in soy hydrolysate formula compensated for the lower bioavailability and resulted in similar amounts of calcium and zinc retained.     

Antigenicity of infant formulas: role of immature intestine on protein permeability

Preliminary studies of 25 infants fed casein hydrolysate, soy-based or milk-based formulas were undertaken to determine the importance of age with respect to the relative antigenicity of formula proteins. Infants fed casein hydrolysate for the first three months had lower antibody titers (hemagglutinins) to subsequent milk-based or soy-based proteins than those given these formulas since birth. The clinical implications with regard to atopy and gastrointestinal protein intolerance are discussed. Soy protein is at least as antigenic as milk protein and should be used with caution in prophylaxis against possible dietary antigen/antibody-related disease.     

Problems of early infancy, formula changes, and mothers' beliefs about their infants

Problems of early infancy are sometimes managed by changing an infant's formula from a cow milk formula to a soy protein or casein hydrolysate formula ("special formulas"). This study was designed to determine the frequency of formula changes, mothers' reports of problems that lead to such a change, and mothers' beliefs about the causes of these problems. Mothers of 189 breast-feeding (BF) and 184 formula-feeding (FF) infants were enrolled postpartum. Follow-up data were obtained by telephone interviews at 4 months. After starting a cow milk formula, 11% of the BF and 25% of the FF infants were given special formulas. Mothers frequently reported problems related to feeding, bowel movements, and crying behavior; 32% of infants with such problems were given special formulas. Excessive crying and colic were the most common problems leading to a formula change. When a formula was changed, mothers more frequently believed that the cause of the problem was intrinsic to the child (P less than 0.001) and that their infant had had a "disease or illness" (P less than 0.001). When formula changes occurred, 26% of mothers believed that their infants were allergic to cow milk. These beliefs may affect a mother's perceptions of her child's vulnerability.     

Hypersensitivity reaction in an infant fed hydrolyzed lactalbumin contained in a semielemental formula

Following introduction of milk protein formula feedings, a 6-month-old male developed profuse, watery diarrhea progressing to shock, requiring cardiopulmonary resuscitation. Reinstitution of enteral feedings with a formula containing hydrolyzed lactalbumin (Travasorb STD) resulted in recurrence of diarrhea with fever. Intestinal and rectal biopsies showed only nonspecific inflammatory changes. He was discharged on an elemental formula (Vivonex). Twenty-three months later, while admitted for evaluation of hypophosphatemic rickets, immunologic testing using the lymphocyte migration inhibition factor (LIF) test demonstrated positive reactions, especially to alpha-lactalbumin (56% inhibition) and whole cow's milk (22%, normal of less than 20% inhibition). Skin tests revealed sensitivity to cow's milk and eggs. Soy formula also produced diarrhea and bloody stools. Protein hydrolysate formulas, touted as hypoallergenic diets, are useful in infants with intolerance to milk protein. This is the first documented case of an immunological reaction to the hydrolyzed whey protein, lactalbumin. Although protein hydrolysate formulas are effective treatment in most infants with milk protein intolerance, allergic reactions are possible. Caution and close observation should be exercised in immunologically sensitized infants rechallenged with any formula.     

Protein hydrolysates: hypoallergenic milks and extensively hydrolyzed formulas. Immuno-allergic basis for their use in prevention and treatment of milk allergy]

Allergy to milk has an estimated incidence of 2.5%. Hypoallergenic milks are partial hydrolysates of proteins with lactose. Extensive hydrolysates of casein are mainly small peptides and do not include lactose in their formula. A primary allergenicity as well as a cross-sensitivity are shown for all partial hydrolysates. Even extensive hydrolysates have a weak potential of cross-allergy. The prevention of cow's milk allergy in infants at peculiar risk, born from atopic parents, is based on breast-feeding and/or partial or extensive hydrolysates. There is no conclusive evidence for the usefulness of eviction of dairy products during pregnancy or during the period of breast-feeding. The treatment needs exclusively extensive casein hydrolysates ensuring a 90% protection with 95% confidence intervals. Predictive prick tests in certain cases may help the choice of another hydrolysate. Severe cases with failure to thrive or multiple food intolerance require an amino-acid based formula (Neocate). A rational diversification of the diet is advised in order to prevent the onset of a multiple food intolerance syndrome which could avert from the recovery of cow milk allergy.     

Gastric electrical activity and gastric emptying in preterm newborns fed standard and hydrolysate formulas

BACKGROUND: Because infant formulas containing hydrolyzed cow milk protein are used to reduce feeding intolerance and to improve gastric emptying, the effect on gastrointestinal motility of a hydrolysate formula was compared with that of a standard preterm formula. METHODS: Thirty-six preterm newborns with a gestational age of 32.2 +/- 2.3 weeks were assigned randomly to standard formula or hydrolyzed formula. Cutaneous electrogastrography and ultrasound examination of gastric emptying were performed simultaneously to evaluate gastrointestinal motility before and after the test meal. All recording sessions were performed 1 week after infants had reached full enteral feeding. RESULTS: No significant difference in gastrointestinal symptoms was noted in the newborns fed the different formulas. In particular, regurgitation and vomiting were observed in 78% versus 64% of preterm newborns after standard and hydrolyzed formula, respectively (Fisher exact test, not significant). No differences were found in terms of gastric electrical activity and gastric emptying time between the two groups. CONCLUSIONS: It seems unnecessary to use hydrolysate formulas to improve motility in preterm infants.     

Cow's milk protein-sensitive enteropathy. Clinical and histological results of the cow's milk provocation test

Nineteen infants suspected of having cow's milk protein-sensitive enteropathy were studied. They all showed failure to thrive, diarrhoea and/or vomiting when fed a diet of cow's milk, and improved when their diet was changed to casein hydrolysate. Jejunal biopsy was done before and 18--23 hours after a milk challenge. Of the 19 infants, 12 presented histological evidence of cow's milk protein intolerance. Eight suffered from vomiting and diarrhoea within 9 days of the milk challenge, but in 4 cases the histological abnormalities were not accompanied by clinical symptoms. In one case a chicken meat intolerance was documented. The histological appearance of the intestinal mucosa after chicken challenge was identical to that observed after milk challenge. In our opinion, repeated intestinal biopsies before and after an acute challenge is the best method to establish the diagnosis not only of cow's milk protein intolerance but also of intolerance to other alimentary proteins.     

Use of infant formulas in infants with cow milk allergy

Allergic (immune-mediated) reactions to cow milk and other dietary proteins encountered during infancy are responsible for some of the adverse symptoms and syndromes observed in infants intolerant to cow milk, infant formulas and occasionally human milk. Iron deficiency anemia associated with gastrointestinal blood loss, protein losing enteropathy, enterocolitis, colitis, and malabsorption syndrome are examples of putative allergic reactions to dietary antigens which occur in infancy. A number of symptoms referable to the gastrointestinal tract such as, vomiting, colic and chronic non-specific diarrhea occur in infants both with and without immune-mediated reactions to dietary antigens. Verification of adverse reactions to dietary antigens, including allergic reactions, should be accomplished through the use of double-blind, placebo-controlled food challenge, with the dietary antigen to be tested presented in a liquid vehicle or, in older children, in capsule form. Approximately 8%–25% of children with immediate hypersensitivity to cow milk have been found to be allergic to soy products. Soy and other intact protein substitutes for cow milk, such as beef and lamb based formulas, have produced anaphylactic reactions both in human infants and in animal models. Hypoallergenic formulas should have a chemically modified protein base which demonstrates significant reduction in anti-genicity when tested in the laboratory both in vitro and in vivo. Such formulas should meet rigorous standards for hypoallergenicity in clinical testing in human allergic infants or infants at high risk for developing allergy before being labelled hypoallergenic.     

Antigenicity and allergenicity of cow milk hydrolysates intended for infant feeding

Allergenicity and antigenicity of various commercially available cow milk hydrolysates intended for infant feeding were analysed in 45 children with cow milk allergy. The hydrolysates included the whey hydrolysates Beba HA® (Good Start HA®) and Profylac®, and the casein hydrolysates Alimentum® and Nutramigen®. Positive skin prick tests were recorded against Beba HA in 10 of 41 tested children (24%), against Profylac® in 5/34 (15%) and in one each (2.5%) against Alimentum and Nutramigen. Double-blind placebo-controlled oral challenge tests were performed in 11 children with cow milk allergy using Alimentum, cow milk (positive control) and their regular well-tolerated formula (Nutramigen or soy) used as negative control. One child reacted to Alimentum. This patient was the only one with circulating antibodies against the product, as indicated by a positive RAST. High density SDS-PAGE electrophoresis showed that Beba HA contained a number of unresolved proteins, and non-degraded or partially degraded whey proteins in the range of 5–20 kD. Profylac contained strongly stained protein material in the low molecular weight region 1–10 kD. No protein bands could be identified in the casein-based hydrolysates. Residual antigenicity was tested by measuring the content of betalactoglobulin in the hydrolysates. Three of the hydrolysates contained < 0.06 μg/g dry weight, while the concentration in Beba HA was 200 μg/g dry weight. Positive RAST against Beba HA was detected in 11/45 sera (24%) compared to 7–13% against the other hydrolysates. RAST inhibition with the hydrolysates using cow milk discs was very low for all of them. Using dot immuno-binding assay a weak IgE binding with Alimentum was detected in 4 sera, Beba HA and Profylac in each 2 sera and with Nutramigen in one. The data taken together show that all 4 tested hydrolysates retain some allergenicity. There were differences between the products, one of the whey hydrolysates being substantially more allergenic and antigenic than the other tested formulas. The casein hydrolysate Alimentum showed few reactions in vivo and in vitro in this selected group of children but one child reacted when challenged with Alimentum, indicating that there is a risk for general reactions when using any hydrolysed product in subjects allergic to cow milk.     

Plasma amino acid and protein concentrations in infants fed human milk or a whey protein hydrolysate formula during the first month of life

The aim of the study was to compare growth parameters, biochemical indices of protein metabolism and plasma amino acid concentrations in infants fed either human milk ( n = 12) or a whey protein hydrolysate formula ( n = 13) during the first month of life. Growth and gain in skin fold thickness were similar in both groups whereas serum protein concentration was significantly decreased (57.4 ± 3.9 versus 61.2 ± 2.9 g/l) in the infants fed the whey hydrolysate formula. The discrepancies between the plasma amino acid pattern of the whey hydrolysate formula group and that of the human milk group lessened during the first month. Nevertheless, at a mean age of 33 days the plasma threonine concentration remained twice as high and the plasma tyrosine, phenylalanine and proline concentrations were Significantly lower in the whey hydrolysate formula group than in the human milk group. Thus, compared with breast-fed infants, growth and most of the biological indices of protein metabolism were satisfactory in infants fed during the first month of life on a whey protein hydrolysate formula. Nevertheless, the decrease in total plasma protein concentration needs to be confirmed in a larger cohort of infants. In addition, further research is necessary to investigate the possible ways of reducing the hyperthreoninemia and preventing other plasma amino acid disturbances since it would be desirable to obtain plasma amino acid levels similar to those of breast-fed infants.     

Growth of infants with IgE-mediated cow''s milk allergy fed different formulas in the complementary feeding period

Observational studies have shown that allergic infants, irrespective of the type of diet, show various degrees of growth depression in the first year of life. We investigated whether the type of milk in the complementary feeding period (6-12 months of age) is associated with differences in the increase of standardized growth indices (weight-for-age, WA; length-for-age, LA; and weight-for-length, WL, z-scores) in infants with cow's milk allergy (CMA). Infants with immunoglobulin E-mediated CMA breastfed at least 4 months and progressively weaned in the 5- to 6-month period were randomly assigned to three special formulas, a soy formula (n = 32), a casein hydrolysate (n = 31), and a rice hydrolysate (n = 30). A fourth, non-randomized group was made up by allergic infants still breastfed up to 12 months (n = 32). Groups were compared for WA, LA, and WL z-scores at 6, 9 and 12 months of age. All groups showed low WA and LA z-scores at 6 months of age. Infants fed hydrolyzed products showed a trend toward higher WA z-score increments in the 6- to 12-month period. The use of casein- and rice-based hydrolyzed formulas resulted in higher changes in WA compared with soy formula. Further research should be aimed at optimizing the dietary needs and feeding regimens for infants with CMA.     

Evaluation of infant feeding in acute gastroenteritis

Sixty-eight bottle-fed babies under 9 months of age with mild acute gastroenteritis were observed to evaluate current feeding regimens following acute gastroenteritis in infancy. All babies were fed for 24 h with a glucose-electrolyte mixture (GEM) and then randomly assigned to either a gradual reintroduction to their normal milk, i.e., slow regrade; immediate return to full-strength formula; or a rapid regrade to a hypoallergenic whey hydrolysate formula. All groups were well matched for age, sex, ethnic origin, nutritional state, and degree of hydration. There was no significance difference in stool frequency or reducing substances, vomiting, and duration of hospital stay between the three groups. Many infants (6/24) refused to take the whey hydrolysate formula, presumably because of unpalatability. Weight gain was more rapid when full-strength milk was given. Clinical relapse developed in 12 (17%) of patients. An enteric pathogen was detected in eight of this group and cow's milk protein intolerance in three (one from each feeding group). No infant had clinically significant lactose intolerance, in marked contrast to previous experience at Queen Elizabeth Hospital. In this group of previously healthy, well-nourished babies with mild acute gastroenteritis, there was no advantage in regrading slowly to milk or a hypoallergenic formula. An immediate return to normal formula 24 h after GEM feeding was well tolerated and simpler for parents.     

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.     

Allergic gastroenteropathy in preterm infants

OBJECTIVES: To determine the clinical presentation, histopathologic features, and outcome of biopsy-proven allergic gastroenteropathy (AGE) in preterm infants. We hypothesized that AGE is a more frequent cause of gastrointestinal disease in this population than previously suspected. STUDY DESIGN: The retrospective portion of the study, from 1992 to 1997, included preterm infants <37 weeks' gestation who underwent biopsy because of suspected AGE. The prospective portion, from January to December 1998, included 20 infants undergoing endoscopy and biopsy because of suspected AGE. RESULTS: Twenty-five infants (12 retrospective/13 prospective) with mean gestational age of 29 weeks at birth and mean postnatal age at diagnosis of 78 days were diagnosed with AGE. Three clinical patterns of presentation were noted: group 1, gastroesophageal reflux disease (n = 5); group 2, non-specific feeding intolerance (n = 8); and group 3, lower gastrointestinal bleeding (n = 12). Ten patients had negative biopsy findings (3 retrospective/7 prospective) and had clinical features indistinguishable from those of groups 1 and 2. Patients in group 3 were most likely to have positive biopsy findings (12 of 12). Fifteen patients responded to a casein hydrolysate formula, and 10 patients required an amino acid-based formula. Patients with AGE who had eosinophilic infiltration and villous atrophy took longer to recover than those with eosinophilic infiltration alone (P <.03). Subsequently, most have tolerated formula challenges and are currently tolerating cow's milk. CONCLUSIONS: AGE may be an under-recognized cause of gastrointestinal symptoms in preterm infants. Confirmation with endoscopy and biopsy can be done safely and provides the basis for appropriate dietary management.