Safety and efficacy of a new extensively hydrolyzed formula for infants with cow's milk protein allergy

Cow's milk protein allergy (CMPA) is best treated by complete elimination of cow's milk from the diet. For infants with CMPA who cannot be breast-fed, formulas based on extensively hydrolyzed proteins or on amino acids are the preferred substitutes for cow's milk-based formulas. In this study, we compared the tolerance and growth of infants with CMPA who were fed a new extensively hydrolyzed formula containing lactose (eHF) with those who were fed an amino acid formula (AAF). This was a prospective, multi-center, randomized, reference-controlled study. Seventy-seven infants <12 months old with suspected CMPA were enrolled. In 66 of these, CMPA was confirmed by oral challenge in a double-blind, placebo-controlled food challenge (DBPCFC) or by a medical history of severe allergic reaction to cow's milk and a positive skin prick test. These infants were then tested for their reaction to eHF and AAF in a DBPCFC. All infants tolerated both formulas and were randomized to receive either eHF (n = 34) or AAF (n = 32) for 180 days. Growth (weight, length, and head circumference) and tolerance [skin, gastro-intestinal, and respiratory tract symptoms of allergy] were evaluated after 30, 60, 90, and 180 days. There were no significant differences between the two groups in any of the growth measurements. Length and head circumference were similar to Euro-growth standards, but weight was slightly lower. Gastro-intestinal and respiratory tract symptoms of allergy were also similar in the two groups. However, whereas SCORAD scores for atopic dermatitis remained constant throughout the study in infants-fed eHF, there was a slight decrease in those fed AAF. Infants-fed eHF had significantly fewer incidents of vomiting than infants-fed AAF and a significantly higher frequency of soft stools. The new eHF is safe and well tolerated in infants diagnosed with CMPA.     

Allergy to extensively hydrolyzed cow's milk proteins in infants: safety and duration of amino acid-based formula

Infants (n = 52) allergic to cow's milk protein and extensively hydrolyzed formulas received an amino acid-based formula. The amino acid-based formula proved to be safe, with infants exhibiting an overall gain in length and weight. Children with allergy restricted to extensively hydrolyzed formulas were diagnosed earlier and tolerated cow's milk protein earlier than children with multiple food allergy.     

Safety and efficacy of a new extensively hydrolyzed formula for infants with cow's milk protein allergy.

Cow's milk protein allergy (CMPA) is best treated by complete elimination of cow's milk from the diet. For infants with CMPA who cannot be breast-fed, formulas based on extensively hydrolyzed proteins or on amino acids are the preferred substitutes for cow's milk-based formulas. In this study, we compared the tolerance and growth of infants with CMPA who were fed a new extensively hydrolyzed formula containing lactose (eHF) with those who were fed an amino acid formula (AAF). This was a prospective, multi-center, randomized, reference-controlled study. Seventy-seven infants <12 months old with suspected CMPA were enrolled. In 66 of these, CMPA was confirmed by oral challenge in a double-blind, placebo-controlled food challenge (DBPCFC) or by a medical history of severe allergic reaction to cow's milk and a positive skin prick test. These infants were then tested for their reaction to eHF and AAF in a DBPCFC. All infants tolerated both formulas and were randomized to receive either eHF (n = 34) or AAF (n = 32) for 180 days. Growth (weight, length, and head circumference) and tolerance [skin, gastro-intestinal, and respiratory tract symptoms of allergy] were evaluated after 30, 60, 90, and 180 days. There were no significant differences between the two groups in any of the growth measurements. Length and head circumference were similar to Euro-growth standards, but weight was slightly lower. Gastro-intestinal and respiratory tract symptoms of allergy were also similar in the two groups. However, whereas SCORAD scores for atopic dermatitis remained constant throughout the study in infants-fed eHF, there was a slight decrease in those fed AAF. Infants-fed eHF had significantly fewer incidents of vomiting than infants-fed AAF and a significantly higher frequency of soft stools. The new eHF is safe and well tolerated in infants diagnosed with CMPA.     

Insomnia and cow's milk allergy in infants

A group of eight infants (six boys and two girls, 7 to 46 weeks of age) is reported, in whom a causal relationship between cow's milk allergy and chronic sleeplessness was suspected. They were referred because of waking and crying episodes that had occurred since the early days of life during sleep hours. During an average night, they slept about 4.5 hours and woke their parents about five times. They cried a lot during the day and were described as fussy. Two infants had been treated with phenothiazine without improvement. No cause for chronic insomnia was found during a standard medical and psychologic workup. An all-night polygraphic recording confirmed the disrupted sleep pattern of these infants, as compared with that of normal infants, and excluded further causes of arousals. Due to a clinical suspicion of atopy, the infants were further subjected to a series of allergy tests. IgE levels were shown to be elevated in each child, and radioallergosorbent tests were positive for cow's milk protein. The infants were than fed exclusively with a hydrolyzed milk protein mixture for 4 weeks. Sleep normalized within 2 weeks in every infant: night sleep increased to a median of 10 hours, and the awakenings only occurred occasionally. In four infants less than 6 months of age, cow's milk was reintroduced in the diet, and within 1 week all four became severely sleepless. Cow's milk was again excluded from the diet and the babies' sleep behaviors were again normalized. It is concluded that, when no evident cause for sleeplessness can be found in an infant, the possibility of milk allergy should be given serious consideration.     

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).     

Lymphocyte response to cow's milk proteins in patients with cow's milk allergy: relationship to antigen exposure

The cellular immune response to cow's milk was measured in patients with challenge-proven cow's milk allergy (CMA), manifested with either gastrointestinal or skin symptoms. After 2–4 weeks on milk elimination, 44 children, mean (SD) age 15.7 (9.4) months, were challenged, and cow's milk-induced lymphocyte transformation was measured before the clinical challenge (Day 1) and / or one week later (Day 8). During the clinical challenge period, 17 (39%) patients showed gastrointestinal reactions, 9 (20%) had urticarial or eczematous skin eruptions, and 18 (41%) were negative to challenge. On Day 1, the mean [95% confidence interval] stimulation index for lymphocytes in patients manifesting CMA with gastrointestinal symptoms, 2.60 [1.60, 4.10], was significantly higher than that in patients with skin symptoms, 1.15 [0.60, 2.30], or patients with negative clinical challenge, 0.83 [0.64, 1.08], F = 9.0, p = 0.001. After the clinical challenge (Day 8), this cow's milk-induced lymphocyte proliferation response was abrogated. At the same time, CMA patients evidenced a significantly higher spontaneous lymphocyte proliferation response in RPMI medium-containing control cultures than those with negative clinical challenge. We conclude that in patients with CMA, the number of circulating cow's milk-sensitized lymphocytes is depleted or their function is impaired after clinical exposure to cow's milk antigens.     

Soy allergy in infants and children with IgE-associated cow's milk allergy

OBJECTIVES: To determine the prevalence of soy allergy in IgE-associated cow's milk allergy (CMA). STUDY DESIGN: Children <3.5 years with documented IgE-associated CMA (n = 93) were evaluated for soy allergy by double-blind, placebo-controlled food challenge, open challenge, or convincing previous history of an anaphylactic reaction to soy. Children tolerant to soy at entry received soy formula and were followed up for 1 year. RESULTS: Of this IgE-associated CMA cohort (ages 3 to 41 months), 14% (95% CI = 7. 7%-22.7%) were determined to have soy allergy, 12 definitely at entry and 1 possibly after 1 year of soy ingestion. The latter child experienced severe failure to thrive at enrollment and exhibited improved growth while receiving soy during follow-up but was diagnosed with eosinophilic esophagitis at study completion. Improved growth (P <.05) occurred in the non-soy-allergic cohort ingesting soy formula (579 31 mL/d) during the year of follow-up. CONCLUSIONS: Soy allergy occurs in only a small minority of young children with IgE-associated CMA. As such, soy formula may provide a safe and growth-promoting alternative for the majority of children with IgE-associated CMA shown to be soy tolerant at the time of introduction of soy formula.     

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.     

Vomiting and gastric motility in infants with cow's milk allergy

BACKGROUND: Regurgitation and vomiting are common manifestations of cow's milk protein allergy (CMPA) in infants and are usually ascribed to gastroesophageal reflux (GER). Gastric anaphylaxis can induce antral dysmotility in the rat, and therefore the hypothesis for the current study was that cow's milk in sensitized infants may impair antral motility, thereby promoting GER and reflex vomiting. METHODS: Seven vomiting infants with CMPA and nine with primary GER underwent a challenge with cow's milk formula. Electrogastrography (EGG) was used to measure the spectral frequency (bradygastria = 1.5-2.4 cycles per minute [cpm], normogastria = 2.5-3.9 cpm, tachygastria = 4.0-9.0 cpm) and the postprandial-to-fasting power ratio of gastric electrical activity, whereas gastric half-emptying time (T1/2) was measured by electrical impedance tomography (EIT). RESULTS: In CMPA and GER, respectively, during fasting, the frequency distribution (mean +/- SD) of the EGG was as follows: normogastria 47.9%+/-12.5% versus 52.2%+/-9.8%, bradygastria 24.1%+/-5.7% versus 22.8%+/-8.3%, and tachygastria 28.0% 8.5% versus 25.0% 8.3%. In contrast, after the cow's milk challenge, the difference between the two groups was statistically significant: normogastria 33.1%+/-8.8% versus 70.6%+/-8.6% (P < 0.0001). bradygastria 38.0%+/-15.5% versus 15.7%+/-5.2% (P = 0.002), and tachygastria 28.9%+/-10.6% versus 13.4%+/-4.6% (P = 0.001. The postprandial/ fasting power ratio (mean +/- SD) was 3.2+/-1.9 in CMPA and 8.1+/-2.1 in GER (P < 0.0001). Gastric T1/2 (mean +/- SD) of the cow's milk meal was 89.0+/-26.3 minutes versus 54.0+/-12.6 minutes (P = 0.003). In infants with GER all EGG parameters and gastric T1/2 were similar to that in 10 healthy control infants. CONCLUSIONS: In sensitized infants, cow's milk induces severe gastric dysrhythmia and delayed gastric emptying, which in turn may exacerbate GER and induce reflex vomiting. Electrogastrography and EIT can be useful in the assessment of vomiting, GER, and CMPA in infants.     

水解蛋白配方与婴幼儿牛奶过敏的预防和治疗

食物过敏是婴幼儿最早出现的过敏问题,牛奶是婴幼儿最常见的过敏食物。牛奶过敏的临床表现多种多样,可涉及皮肤、呼吸道、消化道等多器官多系统。母乳喂养是过敏高风险婴儿的首选喂养方式,但对不能进行母乳喂养的婴儿应选择适当的低敏配方奶,水解蛋白是获得低敏配方的最好方法。根据水解的程度,水解蛋白配方分为适度水解蛋白配方和完全水解蛋白配方。完全水解配方被推荐用于牛乳蛋白过敏婴儿的治疗,适度水解配方通常推荐用于特应质高风险婴儿的初级干预。     

Intestinal cow's milk allergy

Cow's milk allergy (CMA) is multifaceted disease representing systemic, skin or gastrointestinal reactions to cow's milk (CM) protein. This article shortly reviews the intestinal form of CMA (ICMA). According us the child is allergic to CM when the immunologic reaction to CM is associated with clinical symptoms. The incidence of CMA is 1.3-1.9% in general, but the ICMA only 0.6 pro mille among the children less than six months of age. The majority of infants shows symptoms within a month of starting CM feeding. The majority of children with CMA have gastrointestinal symptoms. Manx of these infants has additionally dermatological symptoms and some respiratory symptoms. The mode of onset is often acute diarrhoea and vomiting, as in acute gastroenteritis. Laboratory findings indicate iron deficiency anemia in 20-70%. Half to two thirds of infants with chronic diarrhoea have moderate to severe steatorrhoea. The morphologic lesion in the gastrointestinal tract in ICMA is widespread, often being present from stomach to rectum. Jejunal lesion is most severe in the proximal part of the intestine and nowadays most patients have only partial villous atrophy or slight changes of the villi. Both the epithelium and the lamina propria of the jejunum are infiltrated with inflammatory cells. The morphology of the small intestine speaks for a strong immune reaction which leads increased destruction of surface epithelial cells. We recommend elimination of CM proteins to the age of 1.5 to 2 years. Most patients tolerate CM by the age of 2 years without symptoms. Prolonged breast-feeding and avoidance of early contact with CM are important in reducing the severity and frequency of CMA.