低敏配方在牛奶蛋白过敏患儿中的应用

近年来,食物过敏(food allergy,FA)的发病率呈持续上升趋势.据报道,每12名婴幼儿中就有1名患有食物过敏,其中牛奶蛋白过敏(cow's milk protein allergy,CMPA)最为多见.CMPA是指由牛奶蛋白引起的异常或过强的免疫反应.现有资料显示CMPA的发病率约为2%～3%,年龄多集中在2岁以下~([1]).     

Soy protein intolerance: four patients with concomitant cow's milk intolerance

An infrequently encountered and poorly understood infantile disorder is gastrointestinal soy protein intolerance. Four patients who had intractable diarrhea of infancy and who failed to thrive were tested by oral challenge with soy protein isolate and were found to have soy protein intolerance. All four exhibited concomitant sensitivity to cow's milk protein. The response to challenge with soy protein included diarrhea, vomiting, hypotension, lethargy, and fever. These symptoms were immediate, of short duration, and occurred with each subsequent challenge dose. No patient exhibited cutaneous, pulmonary, or hematologic evidence of allergy although it was prominent in their families. A diet devoid of intact soy and cow's milk protein allowed symptomatic recovery and rapid weight gain. Oral disodium cromoglycate therapy was ineffective in one trial. Soy protein intolerance should be suspected in infants with diarrhea resistant to therapy with soy based formulas.     

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。     

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.     

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.     

Leucocyte migration inhibition in cow's milk protein intolerance

The leucocyte migration inhibition (LMI) was determined in an assay after in vitro challenge with beta-lactoglobulin. The assay was considered positive when migration inhibition index was greater than 20% (mean +3 SD of healthy infants). Ninety-eight infants with protracted diarrhoea and failure to thrive, 16 healthy, 12 malnourished, and 16 infants suffering from acute gastroenteritis were studied. Of the 98 patients with protracted diarrhoea, 12 fulfilled Goldman's criteria for cow's milk protein intolerance, 63 had lactose malabsorption, and in 15 no associated causative factor was identified. The mean index of migration inhibition in the cow's milk allergic group (58.83 +/- 11.98) was higher than in healthy controls (8.25 +/- 3.91), the difference being statistically significant (p less than 0.05). The test was positive in all patients with cow's milk protein intolerance. The assay was also positive in four other patients suffering from protracted diarrhoea, two of whom had lactose malabsorption. All the infants with acute gastroenteritis and malnutrition had values within the normal range. The migration inhibition index in five patients with cow's milk intolerance had declined to 24.74 +/- 4.87 in assays performed 1-6 weeks after return of clinical tolerance to cow's milk (p less than 0.05) but the test was still within the positive range in three of the five infants. These results suggest that this cell mediated immune assay is a sensitive test for the diagnosis of cow's milk protein intolerance in infants. The specificity needs to be reassessed in the light of more objective criteria for the diagnosis of cow's milk protein intolerance.     

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.     

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.     

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.     

Impaired gastric function in children with cow's milk intolerance

Eight infants with cow's milk intolerance (CMI) were studied for basal and maximal gastric acid secretion and the fasting serum gastrin level. All these patients had clinical malabsorption. Jejunal biopsies revealed subtotal villous atrophy in six children and slight changes in the remaining two.The mean maximal acid secretion in the infants with CMI was significantly decreased, being 85±78 mol/h/kg (mean ± SD), as compared with a control group of the same age with a corresponding value of 233±66 mol/h/kg. The fasting serum gastrin level was elevated, being 104±116 pmol/l in the study group and 37±10 in the controls.Three infants with CMI underwent gastric biopsy. Marked changes with epithelial degeneration and prominent cellularity in the lamina propria were seen in two patients. The injury was most severe in the antrum of the stomach.When these patients with CMI were treated with human or soy milk, the maximal acid secretion returned normal in six months.     

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.     

Gastrointestinal occult hemorrhage and gastroduodenitis in cow's milk protein intolerance

We are reporting on four infants with cow's milk protein intolerance who presented with hypochromic anemia and occult gastrointestinal hemorrhage. Esophagogastroduodenoscopy revealed erosive gastritis or gastroduodenitis in all cases. Management with a cow's milk-free diet led to a favorable clinical and hematological outcome; the endoscopic inflammatory image disappeared after the cow's milk-free diet trial. Challenge with cow's milk led to gastrointestinal symptoms and to impaired D-xylose absorption. The data presented suggest that some patients with cow's milk intolerance may have gastroduodenitis resulting in occult gastrointestinal hemorrhage and hypochromic anemia.     

Time course of allergy to extensively hydrolyzed cow's milk proteins in infants

We report on the follow-up of 22 infants allergic to cow's milk proteins who did not tolerate extensively hydrolyzed protein formulas. After successful use of an amino acid-based diet for a duration of 11.8 +/- 8.7 months, evolution differed according to the presence or absence of associated allergy to other foods. Cow's milk protein tolerance occurred earlier in the patients (n = 9) whose allergy was limited to cow's milk proteins and to extensively hydrolyzed protein formulas.