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.     

Differentiation of cows' milk intolerance and gastro-oesophageal reflux.

The aim of this study was to compare a non-invasive test of small bowel permeability with a more invasive approach involving endoscopy, mucosal biopsy, and oesophageal pH monitoring for rapidly differentiating gastro-oesophageal reflux (GOR) and cows'' milk intolerance in 25 infants with persistent vomiting. Each subject underwent a cellobiose/mannitol permeability study, upper gastrointestinal endoscopy with oesophageal and small bowel biopsies, and a 24 hour pH study. Reflux disease and/or cows'' milk intolerance was responsible for vomiting in 24 (96%) of the subjects. Sixteen (64%) of the infants had GOR alone, four (16%) had GOR and cows'' milk intolerance, and four (16%) had cows'' milk intolerance alone. Morphometric analysis of small bowel biopsies was abnormal in 19% of the patients with GOR alone and in 67% with cows'' milk intolerance with or without GOR. The permeability test was abnormal in only 6% of the patients with GOR but in 100% with GOR and cows'' milk intolerance and in 100% with cows'' milk intolerance alone. The non-invasive permeability study aimed at rapid determination of cows'' milk intolerance should pre-empt a more invasive approach in the evaluation of infants with persistent vomiting.     

Severe lactic acidosis disease disclosing milk-protein intolerance to cows' milk]

The age of discovery and initial symptoms of cow milk allergy can vary. Lactic acidosis is exceptionally associated to this allergy. CASE REPORT: A 32-day-old girl was admitted for a severe malaise with metabolic acidosis and hyperlactacidemia. There were no neonatal or family problems; breastfeeding was stopped on the 25th day. Fever was noted on the 29th day and her mother reported behavior anomalies followed by a severe malaise with unconsciousness between the 29th and 32nd day. At admission, the infant showed a severe neurological distress, hypotonia and lethargy. Infection and neurological imaging were normal. A compensated metabolic acidosis with hyperlactacidemia (5.96 mmol/L) was noted. There was no argument for esophageal reflux nor vagal hypertony; mitochondrial cytopathy was also excluded. After a 24 hours fast, the clinical state gradually improved and normalized at h48. The infant was discharged with a milk protein hydrolysate formula. Her mother attempted to reintroduce cow milk on the 59th and 64th day, but this was immediately followed by allergic manifestations which supported the diagnosis of cow milk allergy. CONCLUSION: Neurological distress and hyperlactacidemia exceptionally reveal this type of intolerance. The mechanism of hyperlactacidemia remains unclear; it is possibly the consequence of severe changes of the intestinal mucosa, an exclusive glycolytic tissue.     

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

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

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

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

Risk of developing atopic disease after early feeding with cows' milk based formula.

A follow up of a cohort of 736 healthy full term children with exposure to cows' milk based formula and breast milk from donors on the maternity ward was performed. The children were divided into three exposure groups according to the feeding patterns on the maternity ward. Group 1 received only mother's milk, group 2 mother's milk and human donors' milk, and group 3 received mother's milk, donors' milk and cows' milk based formula. The children were investigated at 7 years of age, by examining their medical files, and at 11 and 14 years, by questionnaires regarding symptoms of atopic disease. No significant differences between the three groups at follow up were found in the cumulative incidences of atopic diseases. The amount of formula given did not affect the risk of developing atopic disease. Children with a family history of such diseases ran the same risk of subsequent atopic disease whether they were fed formula or breast milk alone. Cows' milk based formula given on the maternity ward does not seem to increase the risk of developing atopic disease.     

Safety of a new extensively hydrolysed formula in children with cow's milk protein allergy: a double blind crossover study

Background

Formulae for infants with cow's milk protein allergy (CMA) should be based on extensively hydrolysed protein. 'Extensively' however is not strictly defined. Differences in molecular weight and peptide chain length may affect its clinical outcome. We studied the safety of a new extensively hydrolysed casein based formula (Frisolac Allergycare^®: FAC) for children with IgE mediated CMA.

Methods

Thirty children, aged 1.5 – 14.8 years old (median 4.9 years) with persistent CMA were enrolled in this double-blind reference product (Nutramigen^®: NUT) controlled crossover study. All had positive skin prick tests (SPT) and IgE mediated allergy, showing immediate reactions after ingestion of small amounts of milk. Twenty-five children also had positive radio allergen sorbent tests (RAST) to cow's milk. Formulae provided consisted of 80% elementary formula in combination with 20% reference or test product. Crossover periods lasted for two weeks. From both products molecular weight (MALDI-TOF method and HPLC) and peptide chain length distribution (adapted Edman degradation) were determined.

Results

Maximum molecular weights of NUT and FAC are 2.1 and 2.56 kDa, respectively. The contribution of free amino acids and small peptides <0.5 kDa is 46% for FAC and 53% for NUT. About 50% of the protein fraction of both products consists of peptides longer than four amino acids. Three children did not complete the study. The other children all tolerated FAC very well; no adverse reactions were reported.

Conclusions

The new extensively hydrolysed casein-based formula (FAC) can safely be used in children with IgE mediated cow's milk allergy.

     

Allergy to soy formula and to extensively hydrolyzed whey formula in infants with cow's milk allergy: a prospective, randomized study with a follow-up to the age of 2 years

OBJECTIVES: We conducted a prospective, randomized study to evaluate the cumulative incidence of allergy or other adverse reactions to soy formula and to extensively hydrolyzed formula up to the age of 2 years in infants with confirmed cow's milk allergy. STUDY DESIGN: Infants (n = 170) with documented cow's milk allergy were randomly assigned to receive either a soy formula or an extensively hydrolyzed formula. If it was suspected that the formula caused symptoms, a double-blind, placebo-controlled challenge (DBPCFC) with the formula was performed. The children were followed to the age of 2 years, and soy-specific immunoglobulin E antibodies were measured at the time of diagnosis and at the ages of 1 and 2 years. RESULTS: An adverse reaction to the formula was confirmed by challenge in 8 patients (10%; 95% confidence interval, 4.4%-18.8%) randomly assigned to soy formula and in 2 patients (2.2%; 95% confidence interval, 0.3% to 7.8%) randomly assigned to extensively hydrolyzed formula. Adverse reactions to soy were similar in IgE-associated and non-IgE-associated cow's milk allergy (11% and 9%, respectively). IgE to soy was detected in only 2 infants with an adverse reaction to soy. Adverse reactions to soy formula were more common in younger (<6 months) than in older (6 to 12 months) infants (5 of 20 vs 3 of 60, respectively, P =.01). CONCLUSIONS: Soy formula was well tolerated by most infants with IgE-associated and non-IgE-associated cow's milk allergy. Development of IgE-associated allergy to soy was rare. Soy formula can be recommended as a first-choice alternative for infants >or=6 months of age with cow's milk allergy.     

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.     

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.     

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.