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 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.     

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.     

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.     

Correlation between skin prick test using commercial extract of cow''s milk protein and fresh milk and food challenges

The skin prick test (SPT) is regarded as an important diagnostic measure in the diagnostic work-up of cow's milk protein allergy. It is not known whether commercial extracts have any advantage over fresh milk. The aims of the study were to (i) compare the diagnostic capacity of SPTs for the three main cow's milk proteins (alpha-lactalbumin, casein and beta-lactoglobulin) with fresh milk and (ii) determine a cut-off that discriminates between allergic and tolerant children in a controlled food challenge. A study was carried out on 104 children consecutively attending two paediatric allergy clinics for suspected cow's milk allergy. A clinical history, SPTs with fresh cow's milk and commercial extracts of its three main proteins and a challenge test were performed on all the children. A study of the validity of the prick test was also performed by taking different cut-off points for fresh milk and its proteins. Twenty-eight of 104 challenge tests (26.9%) were positive. At a cut-off point of 3 mm, fresh milk showed the greatest negative predictive value (98%), whereas casein showed the greatest positive predictive value (PPV, 85%). Calculation of 95% predicted probabilities using logistic regression revealed predictive decision points of 12 mm for lactalbumin, 9 mm for casein, 10 mm for beta-lactoglobulin and 15 mm for fresh cow's milk. We found that the greater the number of positive SPTs for milk proteins, the more likely the positive response to challenge. Having a positive SPT for all three milk proteins had PPV of 92.3% and would seem more clinically useful than any cut-off. Both fresh milk and cow's milk extract of the three main proteins could be useful in the diagnostic work-up of cow's milk allergy. Finding positivity to all three cow's milk proteins seems to be a simpler and more useful way of avoiding oral food challenges.     

The pendulum between food protein-induced enterocolitis syndrome and IgE-mediated milk allergy

The transition from milk protein-induced enterocolitis syndrome to IgE-mediated milk allergy is uncommon. Herein, we describe three infants that suffered from recurrent vomiting and restlessness in response to cow's milk formula with negative skin prick to milk and therefore diagnosed as milk protein-induced enterocolitis syndrome. After recovering and reintroducing cow's milk formula, they developed disseminated urticaria and positive skin prick test to cow milk compatible with IgE-mediated milk allergy. CONCLUSION: An infant that recovers from cow milk food-induced enterocolitis syndrome might develop afterward IgE-mediated cow milk allergy.     

Anaphylaxis to sheep's milk cheese in a child unaffected by cow's milk protein allergy

A 5-year-old atopic boy unaffected by cow's milk protein allergy experienced several anaphylactic reactions after eating food containing “pecorino” cheese made from sheep's milk. Prick-prick tests were strongly positive to sheep's buttermilk curd and `pecorino' sheep's cheese. Skin prick tests to fresh sheep's milk and to goat's milk were also positive, whereas they were negative to all cow's milk proteins, to whole pasteurized cow's milk and to cheese made from cow's milk. Specific IgE antibodies were negative to all cow's milk proteins. Conclusion Sheep's milk and cheese derived from sheep's milk may cause severe allergic reactions in children affected and, as we report, in children not affected by cow's milk protein allergy. Received: 14 January 1997 and in revised form: 20 June 1997 / Accepted: 8 July 1997     

Cow's milk allergic children can present sensitisation to probiotics

Aim: To evaluate sensitivity to different probiotics in children with cow's milk allergy.
Methods: Eighty-five patients (age range: 4 months –12 years) presenting atopic dermatitis (AD) were enrolled. Skin prick test (SPT) responses to three different probiotics preparations (Fiorilac®, Dicoflor® and Reuterin®) were evaluated in addition to relevant food allergens.
Results: Thirty-nine patients out of 85 (45.8%) had a positive skin response to prick test for cow's milk (3 with reaction <3 mm). Of the thirty-six patients with a cow's milk weal reaction >3 mm, twenty-eight (77.8%) had a skin response to Fiorilac®, four patients (11%) to Dicoflor® and four (11%) to Reuterin®. The proportion of SPT reaction to all the investigated probiotics preparations was significantly lower than cow's milk (r = 9.406; p = 0.002). A significantly higher sensitization was observed for Fiorilac® versus Dicoflor® (r = 30.916; p < 0.001) and versus Reuterin® (r = 34.133; p < 0.001).
Conclusion: Probiotic use in patients with cow's milk allergy has to be limited to products that do not contain milk. This should be clearly reported in the label. In selected patients, it is advisable to perform a screening SPT with the product to evaluate its potential contamination with milk.     

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.     

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.     

Serum specific-IgE antibodies to peptides detected in a casein hydrolysate formula

Up to 2. 59% of infants are affected by cow milk hypersensitivity in the first two years of life, although most of these children will "outgrow" their reactivity within 2-3 years. Extensively hydrolyzed ("hypoallergenic") cow milk-based formulae are often recommended as a substitute formula and are generally well tolerated. However, a small minority of cow milk-allergic children experience allergic reactions to the hypoallergenic formulae as well. Utilizing inhibition-ELISAs and sera from patients with IgE-mediated cow milk allergy, we have identified residual protein fractions less than 20 kD in several of the extensively hydrolyzed cow milk-based formulae. Although many of the cow milk allergic children had positive skin prick lests [SPT] to one of the hydrolysate formulae (Nutramigen^ma), the positive skin test result generally did not correlate with clinical reactivity, although the negative predictive value of the negative SPT was excellent. Children with IgE-mediated cow milk allergy and a positive skin prick test to the hypoallergenic formula should probably receive their first dose of the formula in a medical setting so that appropriate therapy can be administered in the unlikely event of an allergic reaction.     

A FOLLOW-UP STUDY OF INFANTS WITH ADVERSE REACTIONS TO COW'S MILK I. Serum IgE, Skin Test Reactions and RAST in Relation to Clinical Course

Abstract. 47 infants with cow's milk sensitivity were followed for a period varying between 6 months to 4 years (mean 28 months). The age at onset of symptoms varied between 14 days to 20 months. The clinical course was studied in relation to reaginic allergy by use of serum IgE, skin prick test and RAST. Infants with an immediate onset of symptoms from the gastrointestinal tract and the skin after cow's milk intake were discerned as a distinct entity having a high frequency of atopy in the family, positive skin tests and positive RASTs to milk (71%). Cases with delayed reactions to cow's milk seldom had a positive RAST or skin test. Most infants of both groups showed an increasing tolerance to milk. In RAST positive infants the RAST-titers increased significantly after onset of symptoms. After having reached a peak the titers subclined in several cases. The titers did not reflect the degree of milk sensitivity during the follow-up period. However, infants who developed high titers seemed to develop tolerance more slowly than infants with low titers.     

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.     

A follow-up study of infants with adverse reactions to cow's milk. I. Serum IgE, skin test reactions and RAST in relation to clinical course

47 infants with cow's milk sensitivity were followed for a period varying between 6 months to 4 years (mean 28 months). The age at onset of symptoms varied between 14 days to 20 months. The clinical course was studied in relation to reaginic allergy by use of serum IgE, skin prick test and RAST. Infants with an immediate onset of symptoms from the gastrointestinal tract and the skin after cow's milk intake were discerned as a distinct entity having a high frequency of atopy in the family, positive skin tests and positive RASTs to milk (71%). Cases with delayed reactions to cow's milk seldom had a positive RAST or skin test. Most infants of both groups showed an increasing tolerance to milk. In RAST positive infants the RAST-titers increased significantly after onset of symptoms. After having reached a peak the titers subclined in several cases. The titers did not reflect the degree of milk sensitivity during the follow-up period. However, infants who developed high titers seemed to develop tolerance more slowly than infants with low titers.     

The role of cow''s milk protein intolerance in steroid-resistant nephrotic syndrome

The role of cow's milk protein intolerance in steroid-resistant nephrotic syndrome was evaluated in 17 children. Cow's milk was excluded from the diet for at least 14 days without changing previously ineffective prednisone dosage. Six patients with minimal change or mesangial proliferation went into remission 3 to 8 days after elimination of cow's milk. After a period of 2-3 weeks of remission, cow's milk challenge was positive in three patients. After one year on a cow's milk-free diet, two of six patients became milk tolerant and are in remission of NS, one of six became steroid-dependent, two of six are still unable to tolerate cow's milk and are in remission on a cow's milk-free diet and one of six children was lost from observation. The role of cellular mechanisms in steroid-resistant nephrotic syndrome is suggested.     

Anaphylactic reaction to goat's milk in a cow's milk-allergic infant

Goat's milk has been used as a substitute for cow's milk in cow's milk-allergic individuals. It is currently advocated for this purpose in writings and internet resources directed at the lay person, and infant formula based on goat's milk is available in many countries. Clinically significant cross-allergenicity between cow's and goat's milk has been noted, but a life-threatening cross-reaction has not been reported. We describe a 4-month-old infant with immunologically documented cow's milk protein allergy but no prior exposure to goat's milk who developed anaphylaxis after the ingestion of commercial goat's milk. Subsequent skin prick testing demonstrated a specific reaction to goat's milk. Thus, the cross-allergenicity between cow's and goat's milk proteins can lead to life-threatening complications. Individuals allergic to cow's milk protein should avoid goat's milk and goat's milk products.     

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.     

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.     

Z-score of weight for age of infants with atopic dermatitis and cow's milk allergy fed with a rice-hydrolysate formula during the first two years of life

Background: Recently, rice-based formulas have been widely used in hypoallergenic diets, but data on nutritional values are scarce. Aim: To evaluate the growth of infants fed with a rice-based hydrolysate formula, compared to those infants fed with a soy formula or an extensively hydrolysed casein formula, in the first 2 y of life. Methods: A total of 88 infants were enrolled between March 2002 and March 2004. Fifty-eight infants with atopic dermatitis (AD) and cow's milk allergy (CMA), confirmed by open challenge, were enrolled as study group: 15 were fed with a rice-based hydrolysate formula (RHF), 17 with a soy-based formula (SF) and 26 with an extensively hydrolysed casein formula (eHCF). Thirty infants with AD without cow's milk allergy were recruited as a control group (CG) and fed with a free diet. Weight was recorded on enrolment and at 3-monthly intervals in the first year of life, and at 6-monthly intervals in the second year. Infants were weighed naked, before feeding, by means of an electronic integrating scale. The z-scores of weight for age were calculated. Statistics: One-way analysis of variance and Student's t -test were used for statistical comparison. Significance was set at p <0.05. Results: No significant differences between the RHF, SF and eHCF groups were observed for the z-score of weight for age during the first 2 y of life, but a significantly lower difference was seen in the RHF group compared to the control group in the intervals 9 mo–1 y ( p =0.025) and 1–1.5 y ( p =0.020) of age. In contrast, the SF and eHCF groups were comparable to the control group, but the eHCF group was significantly lower ( p =0) in the first trimester of life.
Conclusion: Even if our findings show no significant difference between RHF and control, low weight observed in infants fed with RHF raises doubts about the nutritional adequacy of rice-hydrolysate formulas.     

Follow-up of nutritional status and dietary survey in children with cow''s milk allergy

The nutritional status of children with cow's milk allergy was followed during an elimination diet in 19 children (9 boys and 10 girls) beginning at the mean age of two years (range 0.6-4.1 years). The cow's milk allergy had been verified in hospital by a challenge test at a mean age of 0.9 years (range 0.2-1.9 years). Weight, height and laboratory indices to test protein, mineral and vitamin status were measured at three follow-up visits at three-month intervals. In addition to cow's milk allergy all these children had some other food allergies, and six of the 19 children were allergic to soy protein. Only two of the 19 children were given a soy-based formula. In the diets of the other children, cow's milk was replaced by increasing amounts of other foodstuffs and supplementary calcium. At the beginning of the study the relative heights of the children were slightly retarded (-0.6 SD) and remained unchanged during follow-up (-0.8 SD at the end of the study). The relative weights were found to be decreased during follow-up (p less than 0.05). There was a significant reduction in serum prealbumin values; eight of the 19 children showed abnormally low values. Low serum zinc values were seen in 12 children. Serum iron concentration was low in two children and two had high serum alkaline phosphatase values. Seven-day food recording indicated that dietary intake of energy was below the recommendation in some children, but protein intake was high. Some children had low intakes of riboflavin.(ABSTRACT TRUNCATED AT 250 WORDS)