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.     

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.     

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.     

Evaluation of the immunogenicity of protein hydrolysate formulas using laboratory animal hyperimmunization

The rabbit hyperimmunization model has previously been used to evaluate candidate hypoallergenic protein ingredients. Use of the model has been expanded to include the evaluation of protein hydrolysate formulas. Each formula's immunological reactivity was determined by ELISA measurement of formula-specific rabbit antibody. Animals hyper-immunized with formulas containing extensively hydrolyzed proteins (Alimentum, Nutramigen, and Pregestimil) generated very weak immune responses (<100 fold antibody increase). Products containing intact or partially hydrolyzed proteins (Similac, Enfamil, Good Start, Beba HA, and Nidina HA) elicited high level (>10,000 fold increase) immune responses. Immunogenicity results were then compared to measurements of residual antigen content (by inhibition ELISA) and clinical performance. Correlation of formula immunogenicity, antigenicity and clinical performance indicates that the rabbit model is useful for screening "hypoallergenic" formulas to predict allergenic reactivity.     

Specific IgE antibodies to cow's milk and individual cow's milk proteins in children with suspected allergy to cow's milk

Specific IgE antibodies against whole-milk-antigen mixture and against casein, alpha-lactalbumin and beta-lactoglobulin were determined using the radioallergosorbent test (RAST) in 125 sera of children with an initial diagnosis of suspected cow milk allergy. The results of the RAST were correlated with the clinical diagnosis. No specific IgE antibodies could be demonstrated in 98 children. Of these, 20 (20%) showed clinically intolerance to cow milk presumably on the basis of other immunological mechanisms. Specific IgE antibodies could be demonstrated in the sera of 27 children. Of these, 16 (60%) actually showed allergy to cow milk. A statistically significant association with chi 2 test could be established between positive RAST and clinical diagnosis (p = 0.001).     

Comparison of a partially hydrolyzed infant formula with two extensively hydrolyzed formulas for allergy prevention:A prospective, randomized study

The aim of this study was to compare the allergy‐preventive effect of a partially hydrolyzed formula with two extensively hydrolyzed formulas, in infants with a high risk for development of allergic disease. High‐risk infants from four Danish centres were included in the period from June 1994 to July 1995. Five‐hundred and ninety‐five high‐risk infants were identified. High‐risk infants were defined as having bi‐parental atopy, or a single atopic first‐degree relative combined with cord blood immunoglobulin E (IgE) ≥ 0.3 kU/l. At birth all infants were randomized to one of three different blinded formulas. All mothers had unrestricted diets during pregnancy and lactation and were encouraged to breast‐feed exclusively. If breast‐feeding was insufficient, one of the three formulas, according to randomization, was given during the first 4 months. It was recommended not to introduce cow's milk, cow's milk products, and solid foods until the age of 4 months. After the age of 4 months a normal unrestricted diet and conventional cow's milk‐based formula were given when needed. All infants were followed‐up prospectively with interview and physical examination at the age of 6, 12, and 18 months, and if any possible atopic symptoms were reported. If food allergy was suspected, controlled elimination/challenge procedures were performed in a hospital setting. Of 550 infants included in the study, 514 were seen at all visits and 36 were excluded owing to non‐compliance. Of 478 infants who completed the study, 232 were exclusively breast‐fed, 79 received an extensively hydrolyzed casein formula (Nutramigen), 82 an extensively hydrolyzed whey formula (Profylac), and 85 a partially hydrolyzed whey formula (Nan HA), during the first 4 months of life. These four groups were identical in regard to atopic predisposition, cord blood IgE, birthplace, and gender. Exclusively breast‐fed children were exposed less to tobacco smoke and pets at home and belonged to higher social classes, whereas the three formula groups were identical concerning environmental factors. The frequency of breast‐feeding was high; only eight (2%) children were not breast‐fed at all. The three formula groups were identical in regard to duration of breast‐feeding and age at introduction of formula and solid foods. No significant differences were found in the three groups of infants receiving formula milk regarding the cumulative incidence of atopic dermatitis or respiratory symptoms. The cumulative incidence of parental‐reported cow's milk allergy was significantly higher in children fed partially hydrolyzed formula (Nan HA) compared with extensively hydrolyzed formula (Nutramigen or Profylac) at 12 and 18 months (NanHA, 7.1%; Nutramigen, 2.5%; Profylac, 0%; p = 0.033). The cumulative incidence of confirmed cow's milk allergy was 1.3% (three of 232) in exclusively breast‐fed infants, 0.6% (one of 161) in infants fed extensively hydrolyzed formula (Nutramigen or Profylac), and 4.7% (four of 85) in infants fed partially hydrolyzed formula (Nan HA). Partially hydrolyzed formula was found to be less effective than extensively hydrolyzed formula in preventing cow's milk allergy, 0.6% vs. 4.7% (p = 0.05), but because of the small number of cases the results should be interpreted with caution. Compared with other similar studies the frequency of atopic symptoms was low, even though the dietetic intervention did not include either maternal diet during lactation or dietary restrictions to the children after the age of 4 months.     

Hypoallergenicity of an extensively hydrolyzed whey formula

Several different protein hydrolysate-based infant formulas have been promoted as hypoallergenic and considered suitable for the dietary management of cow's milk allergy (CMA). Accepting that none of the hydrolysate-based products is completely safe, the American Academy of Pediatrics (AAP) recommends that these formulas should be tested in a double-blind placebo-controlled setting and tolerated by at least 90% of children with proven CMA. In principle, this recommendation is also endorsed by the European Society of Paediatric Gastroenterology and Nutrition (ESPGAN) and the European Society of Paediatric Allergy and Clinical Immunology (ESPACI). In this two-center study, 32 children with proven CMA were tested with the extensive hydrolysate whey formula Nutrilon Pepti, for comparison with Profylac (extensive) and Nan HA (partial) whey hydrolysate products. Skin-prick tests (SPTs) were, respectively, positive to the three hydrolysate formulas in 19%, 15%, and 32% of children. After oral challenge it was concluded that 97% (95% CI: 85–100%) of the children tolerated Nutrilon Pepti, 94% (95% CI: 75–100%) tolerated Profylac, and 64% (95% CI: 37–81%) tolerated Nan HA. This study demonstrates that the extensive hydrolysates Nutrilon Pepti and Profylac are well tolerated in a population of children with proven CMA and that both products can be considered safe for their intended use. This study confirms that a very small number of children react even to extensively hydrolyzed formulas. SPT prior to oral exposure to the hydrolysate-based formulas can indicate whether a child is at risk of showing reactions to the product. Introduction of new products to these children should be carried out under a doctor's supervision. However, the majority of the SPT-positive children did tolerate the two extensively hydrolyzed whey-based formulas tested.     

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.     

Antigenicity and allergenicity of hypoallergenic hydrolysate for infant nutrition]

The antigenicity/allergenicity of protein components in hypoallergenic formulae is altered by hydrolysis. Two different hydrolysate formulae, hydrolysate 1 = cow milk based; hydrolysate 2 = soya/beef collagen based, were investigated with respect to their specific IgG/IgE binding capacities using the sera of 41 healthy controls, 40 atopic and 12 cow milk allergic subjects. Furthermore, histamine liberation from basophils on incubation with milk proteins and the hydrolysates was measured in 5 healthy and 3 cow milk allergic individuals. Nearly all probands demonstrated specific IgG binding with hypoallergenic formulae. Anti-hydrolysate 1 IgG titres were higher than titres against hydrolysate 2 in the cow milk allergic and healthy populations. Nonhydrolyzed cow milk elicited IgE binding in all cow milk allergic sera. IgE-antibody for hydrolysate 2 could only be demonstrated in one atopic subject. Hydrolysate 1 showed binding capacity for the IgE-antibody of one atopic and 3/12 cow milk allergic patients. Histamine liberation followed in-vitro incubation with both hydrolysates in one out of 3 cow milk allergic subjects and two out of these cases following incubation to unprocessed cow milk protein. A decreased antigenicity/allergenicity can be demonstrated for the two hydrolysates investigated, however antigenic/allergenic reactivity is still present to some degree. Therefore, the therapeutic application of hypoallergenic formulae in patients with specific sensitization to cow milk should be based on the results of the above-mentioned in-vitro parameters and if necessary skin tests and oral challenges.     

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.     

Skin test and RAST in children allergic to common allergens

Ninety children with bronchial asthma were evaluated for the presence of house dust, house dust mite. Aspergillus fumigatus and milk allergy in vivo by prick test (skin test) and in vitro by RAST. Of the 20 children tested for house dust allergy 12 were positive by skin test and six by RAST. Only six were positive by both methods. Of 25 children tested for house dust mite, 16 were positive by skin test, 13 by RAST and 11 by both methods. Of 35 children tested for aspergillus fumigatus, 25 were positive by skin test, 19 by RAST and 11 were positive by both methods. In the case of 10 children under three years of age with known hypersensitivity to milk, all were negative by prick test and three were moderately positive by RAST method. The correlation of skin test with RAST was 65% for house dust, 72% for house dust mite, 37% for aspergillus fumigatus and 70% for milk. Overall correlation of skin test with RAST was 56·7%.     

Colic and the effect of changing formulas: a double-blind, multiple-crossover study

This study investigated the effect of changing the formulas of colicky infants and addressed the methodologic flaws of earlier studies. Attention was paid to issues of designing a blind study, providing a washout period, and measuring and reproducing the effect. In this randomized, double-blind trial, three changes of formula were made: for each of four 4-day periods, colicky infants alternately received a casein hydrolysate formula (Nutramigen) and a formula containing cow milk. Mothers recorded crying in diaries and indicated which crying episodes they considered to have been caused by colic. Nine infants were started on Nutramigen and eight on the cow milk formula. With the first formula change there was significantly less crying and colic in infants when they were fed Nutramigen than when they were fed cow milk (p less than 0.01); with the second change there was less colic when infants were fed Nutramigen (p less than 0.05) but not significantly less crying. By the third change there were no significant differences between formulas. Further analyses demonstrated that there were more clinically meaningful positive responses (a change in crying by at least one third) to Nutramigen than to cow milk (p less than 0.05). However, only one subject had a clinically meaningful response in colic to all three formula changes. These results demonstrate that in some instances, colic improves with elimination of cow milk formula. However, the effect diminishes with time, and only infrequently is the effect reproducible.     

RAST positivity for food in atopic dermatitis

In 113 children with atopic dermatitis RAST results for 9 food mixtures were analyzed. Sixty-eight children (60%) were RAST positive (greater than or equal to ++) for one or more mixture and 87% of those RAST positive had specific IgE for egg and/or cereals and/or legumes. Sensitization to egg, cow milk and meat was more frequent in the first years of life. RAST for the mixture of cereals and each single cereal, performed in 37 children, gave concordant results in 76%; agreement for the positive results was 88%, but only 54% for the negative ones. Breast versus cow milk feeding in the first months of life was not found to affect intensity of the skin manifestations or frequency of RAST positivity for the food mixtures or the respiratory symptoms.     

Evaluation of a casein and a whey hydrolysate for treatment of cow's-milk-sensitive enteropathy

A casein and a whey hyrolysate were evaluated in the management of 18 children with cow's-milk-sensitive enteropathy. This diagnosis was based upon clinical features, an abnormal small intestinal mucosa, i.e. an enteropathy, and a clinical response to cow's milk elimination. Two infants refused to take the whey hydrolysate. The median weight gain was higher in children given whey hydrolysate (19.4 g/day) than the casein hydrolysate (9.8 g/day). All children responded to cow's milk elimination and most has a significant improvement in small intestinal morphology after a cow's-milk-free diet. There was some advantage for the whey hydrolysate on morphometric analysis of their small intestinal mucosal response.     

Follow up study of cow's milk protein intolerant infants

Over a period of 4 years, 88 infants with cow's milk protein intolerance (CMPI) were followed prospectively in order to evaluate the persistence of CMPI and its relationship between either serum IgE levels or RAST results for cow's milk. After exclusion of lactose intolerance, two positive cow's milk elimination challenge tests were considered diagnostic for CMPI. At the age of 1, 2, 3 and 4 years respectively, 85%, 78%, 49% and 33% of the children still were cow's milk intolerant. Initial serum values of IgE 10 kU/l indicated a late development of tolerance to cow' milk proteins. At the age of 4 years, 90% of infants with initial IgE levels <10 k U/l had become tolerant to cow's milk while this was the case for only 47% of infants with initial IgE levels 10 k U/l. Initial RAST results for cow's milk bore no obvious relationship to outcome.     

Identification of immunogenic maize proteins in a casein hydrolysate formula

Cow's milk‐based formulas used for infants with cow's milk allergy are based on hydrolyzed proteins. The formulas that are successful in preventing allergic responses are extensively hydrolyzed. Nevertheless, reactions to such formulas are occasionally reported, and protein material of higher molecular weight than expected has been detected by binding immunoglobulin E (IgE) from patients' sera. This paper presents the identification of high‐molecular‐weight material in the extensively hydrolyzed casein formula, Nutramigen. The material was concentrated by simple centrifugation. The proteins in the pellet were separated by sodium dodecyl sulfate‐polyacrylamide gel electrophoresis (SDS‐PAGE), and protein‐containing bands were analyzed by protein sequencing after electroblotting. The proteins were identified as maize zeins, which are water‐insoluble proteins of apparent M_r 20 000 and 23 000, presumably originating from the maize starch in Nutramigen. Rabbits immunized with this formula developed antibodies against zeins but not against milk proteins. The maize zeins are probably identical to the recently reported components in Nutramigen ( 1 ), detected by binding of IgE from milk allergic patients, but not correlated to clinical allergic reactivity. The clinical relevance of maize proteins in Nutramigen remains to be established.     

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.     

Whey protein hydrolysate formula for infants with gastrointestinal intolerance to cow milk and soy protein in infant formulas

Twenty-one infants less than 6 months of age with gastrointestinal symptoms of cow milk and/or soy protein-based infant formula intolerance (diarrhea in 14, hematochezia in 16, emesis in 8, failure to thrive in 4, and colic in 10) were treated clinically with a whey protein hydrolysate formula. Six patients improved when placed directly on the formula, and 15 remained asymptomatic or improved when given the whey hydrolysate formula following initial treatment with a casein hydrolysate or elemental formula. Eighteen had supporting evidence of an allergic basis for their symptoms, including a family history of allergies in 6, a clinical challenge with the offending formula in 1, laboratory tests consistent with atopy in 11, and/or rectal biopsy with histologic allergic features in 7. The whey hydrolysate formula may be an acceptable alternative to soy or casein hydrolysate formulas in most infants with gastrointestinal symptoms of cow milk and/or formula intolerance.     

Cow milk-specific humoral and cellular immune response in infants with high risk of atopy under feeding a whey hydrolysate infant formula

BACKGROUND: Hypoallergenic infant formulas (HAF) were developed for atopy prevention in infants with high risk of atopy if these cannot be breastfed. HAF mount an antigen-specific immune response in infants. The aim of the study was to analyse the immune response in infants fed with a new infant formula based on a whey hydrolysate (HAF) and to compare it with that of exclusively breastfed controls. PATIENTS AND METHODS: Plasma concentrations of cow milk-specific IgE were analysed in 94 infants with high risk of atopy, 44 were exclusively breastfed, 50 were fed with HAF. In addition, cow milk-specific IgG antibodies (26 breastfed, 30 fed with HAF) as well as proliferation of periph-eral blood mononuclear cells to bovine beta-lactoglobulin (BLG) (41 breastfed, 47 fed with HAF) were tested. Specific IgE and IgG antibodies were determined using enzymoimmunometric assay (Alastat). Cellular proliferation was measured using tritiated thymidine incorporation assay after 6 day stimulation with BLG. RESULTS: Elevated IgE to cow milk antibodies (> 0.35 kU/L) were detected in two infants from the breastfed group and in one from the HAF-fed group. The plasma concentrations of milk specific IgG antibodies in HAF-fed infants were insignificantly higher than those in breastfed ones. No significant difference was found in bovine BLG-specific cell proliferation between both groups. CONCLUSION: Concerning the properties investigated like antigenicity, allergenicity and immunogenicity, the extensively hydrolysed whey based hypoallergenic formula does not significantly differ from mother milk in 6 month-old infants with an increased atopy risk.     

Severe cow's milk induced colitis in an exclusively breast-fed neonate. Case report and clinical review of cow's milk allergy

Cow's milk induced eosinophilic colitis presenting in the first week of life has been reported, but is very rare. The authors describe a 4-day-old female infant who presented with profuse rectal bleeding resulting in a hematocrit fall from 38% to 30% within 8 hr after hospital admission. Sigmoidoscopy revealed colonic mucosa that was red, edematous, and friable, with punctate hemorrhages. Rectal biopsy showed marked eosinophilic infiltration with multifocal hemorrhage. Further history indicated that while the infant had been exclusively breast-fed since birth, the nursing mother had been drinking 4-5 glasses of cow's milk per day since delivery. Prick puncture skin testing of the infant was positive for cow's milk protein. A serum radioallergosorbent test (RAST) for cow's milk protein was positive. The infant's serum IgE was 1.5 IU/ml. Rectal bleeding resolved when the patient was given a casein hydrolysate formula (Nutramigen, Mead Johnson Nutrition, Evansville, IN), and endoscopy one week later showed improvement, with only scattered areas of erythema, and no friability. We conclude that since the infant was exclusively breast-fed, the milk protein must have passed into the breast milk antigenically intact. Prenatal sensitization probably occurred. Cow's milk induced allergic colitis should be considered in the differential diagnosis of colitis in breast-fed neonates.