游离氨基酸配方奶粉在牛奶蛋白过敏患儿中的应用

目的 观察游离氨基酸配方奶粉在牛奶过敏患儿中的应用效果及预后.方法 收集2009年10月- 2010年10月诊断为牛奶蛋白过敏并使用游离氨基酸配方奶粉治疗的31例患儿.应用年龄别身高Z值、年龄别体质量Z值、身高别体质量Z值评价患儿生长发育情况,根据皮肤病变范围、皮损严重程度、主观症状瘙痒和睡眠影响程度,应用特应性皮炎积分(SCORAD指数)评价患儿的湿疹严重程度,采用t检验、Fisher’s精确概率法等统计学方法分析患儿一般资料、治疗前后的Z评分、SCORAD指数、临床症状改善情况及各项实验室检查指标的差异.结果 31例牛奶蛋白过敏患儿年龄(3.46±2.22)个月,在性别、城乡分布、喂养方式上差异均无统计学意义(Pa＞0.05).治疗随访2个月,患儿湿疹有明显改善(SCORAD指数:21.70 ±20.24 vs 2.8 ±4.t=0.51,P=0.00);消化道症状呕吐、腹泻、血便有明显改善(P=0.00,0.02,0.00);低体质量患儿体质量增长显著(年龄别体质量Z值:-0.58±1.08 vs -0.08 ±0.89,P=0.048);治疗前后患儿外周血白细胞[(12.58±4.82)×109L-1 vs(10.36±2.22) ×109 L-1;t=2.32,P=0.024]、嗜酸性粒细胞总数[(1.62 ±2.05)×109 L-1 vs (0.42±0.50) ×109 L-1;t =3.14,P=0.003]明显降低.结论 使用游离氨基酸配方奶粉是治疗牛奶蛋白过敏的有效方法.     

三种低敏配方治疗牛奶蛋白过敏效果评价

目的 通过对牛奶蛋白过敏患儿采用3种低敏配方(游离氨基酸配方、深度水解配方、大豆配方)进行治疗随访,评估各组患儿体格生长及过敏症状改善情况.方法 初诊为牛奶蛋白过敏且无法进行母乳喂养的婴幼儿74例作为干预组,以健康体检儿童21例作为对照组.干预组遵循家长自愿选择原则分别给予游离氨基酸配方、深度水解配方、大豆配方替代治疗.于治疗开始后第1、2、3、6个月对患儿进行体格监测,同时对过敏症状缓解情况进行评估.采用SPSS13.0统计分析干预组与对照组、干预组间儿童体格生长情况及症状缓解程度和速度.结果 经半年随访,大豆配方替代组儿童年龄的体重及身长的体重Z值分别为(-0.43±0.88)、(-0.31±0.78),显著低于游离氨基酸配方替代组[(0.11±0.77)、(0.20±0.69)]、深度水解配方替代组[(0.10±0.62)、(0.18±0.70)]及对照组[(0.22±0.54)、(0.22±0.64)](P＜0.05);而后3者间体格生长差异无统计学意义(P＞0.05).年龄的身长与年龄的头围四组间差异均无统计学意义(P＞0.05).3种低敏配方均可有效缓解过敏临床症状.游离氨基酸配方与深度水解配方治疗皮肤症状效果优于大豆配方(P=0.003);且治疗1个月即可见显著疗效,而大豆配方缓解症状速度较慢(2个月).结论 游离氨基酸配方及深度水解配方均可维持牛奶蛋白过敏患儿正常的体格生长,而大豆配方治疗组生长速度明显不足.3种配方均可有效缓解牛奶蛋白过敏患儿临床症状,且游离氨基酸配方或深度水解配方治疗婴儿湿疹的效果、缓解速度要优于大豆配方.

Abstract：

Objective To compare the growth and symptom remission of infants with cow's milk protein allergy, who were fed with an amino acid formula, an extensively hydrolyzed formula or soy formula. Method Infants who were diagnosed as cow's milk protein allergy and can not be breastfed were enrolled in the intervention group,and were assigned to three special formulae(amino acid formula, extensively hydrolyzed formula or soy formula ) according to the will of parents from March 2009 to March 2010(n= 74).A non-randomized control group was made up of age-matched healthy children(n=21). Anthropometric measurements and symptoms were evaluated after 30, 60,90, and 180 days. The differences of physical growth and the therapeutic effects among each group were calculated by SPSS 13.0 package. Result After 180 days follow-up, the weight for age Z score and length for weight Z score were -0.43±0.88 and -0.31±0.78 in patients fed with soy formula substitute, which were significantly lower than those of patients fed with amino acid formula (0.11±0.77,0.20±0.69),extensively hydrolyzed formula(0.10±0.62,0.18±0.70)and control group(0.22±0.54,0.22±0.64)(P＜0.05).However, there were no significant differences in physical growth among patients fed with amino acid formula, extensively hydrolyzed formula and control group(P ＞0. 05). Moreover, no significant difference was found in length for age and head circumference for age among four groups (P＞0. 05). All hypoallergenic formulae were much helpful in remission of the symptoms of eczema(P＜0.05 ).However,amino acid formula and extensively hydrolyzed formula were more effective and rapid in relieving symptoms than soy formula (1 mo vs 2 mo)(P=0.003).Conclusion Both amino acid formula and extensively hydrolyzed formula can maintain the normal growth of infants with cow's milk protein allergy.While, the growth of patients fed with soy formula was significantly slower than that of the other three groups. All hypoallergenic formulae can be effective in relieving allergy symptoms,and amino acid formula or extensively hydrolyzed formula seems to be superior to soy formula.     

牛奶蛋白过敏患儿的营养干预

目的 分析牛奶蛋白过敏(CMPA)儿童基本情况,探讨个体化应用氨基酸配方粉、深度水解乳清蛋白婴儿配方粉治疗后的干预效果及转归.方法 收集2009年2 -12月在中国医科大学附属盛京医院儿科就诊,符合CMPA诊断的180例患儿为干预对象.在营养门诊对其喂养史、一般情况进行回顾性分析,给予牛奶回避及治疗类配方粉营养干预7d后回访疗效,指导辅食的选择和添加,并随访3个月、6个月后配方粉喂养婴儿的变化及疗效.结果 180例患儿牛奶过敏高发年龄段为＞2 ～4月龄组(64例,占35.5％);母乳喂养者21例(11.7％),非纯母乳喂养者159例(88.3％);有家族史者32例(17.8％);男女比为1.65:1.干预7d后显效比例最高的临床症状为腹泻(61例,占83.6％).3个月后纯氨基酸配方粉喂养76例(占46.0％),深度水解配方喂养54例(占32.7％),适度水解配方奶粉喂养为25例(占15.3％).6个月后喂养主要是纯氨基酸配方(39例,占24.9％),其次为牛奶配方粉(36例,占22.9％).结论 母乳喂养有利于避免婴儿牛奶过敏,营养干预3个月内不宜喂养含牛奶蛋白配方奶粉,营养干预6个月后部分患儿可获牛奶耐受.牛奶过敏患儿喂养配方粉的转归各不相同,应结合患儿家庭经济能力、病情变化等个体化营养干预.     

口服激发试验在牛奶蛋白过敏诊断中的应用

正国外报道1岁以内婴儿牛奶蛋白过敏(cow's milk protein allergy)发生率为2.0%~7.5%~([1]),目前国内尚无确切统计数据。婴儿牛奶蛋白过敏主要表现为皮肤、消化道及呼吸道症状,但因症状缺乏特异性易误诊,凭临床经验诊断的牛奶蛋白过敏高于实际牛奶蛋白过敏的确诊率,导致患儿接受了不必要的饮食回避,而氨基酸配方或深度水解配方的欠佳的口感使患儿每日的摄入总量减少,一定程度上影响了患儿的生长发育,也增加     

牛奶相关症状评分在婴儿牛奶蛋白过敏早期识别中的评价

目的评价牛奶相关症状评分(Co Mi SS)在婴儿牛奶蛋白过敏(CMPA)早期识别中的作用。方法对2015年6月至2016年5月在深圳市妇幼保健院儿科消化门诊就诊疑似CMPA的26例婴儿测定Co Mi SS,回避牛奶蛋白饮食4周症状改善后返院,行牛奶蛋白食物口服激发试验(OFC),通过ROC曲线来测定Co Mi SS灵敏度和特异度,评价其在婴儿牛奶蛋白过敏早期识别中的作用。结果 26例患儿中口服激发试验阳性17例,Co Mi SS平均(7.9±2.8)分;阴性9例,Co Mi SS平均(4.6±1.6)分。确诊CMPA患儿中,表现为湿疹12例(70.6%),血便9例(52.9%),腹泻9例(52.9%),呕吐3例(17.6%),生长发育迟缓3例(17.6%),反复咳喘1例(5.9%),哭闹1例(5.9%)。两组Co Mi SS差异有统计学意义(Z=-2.926,P0.05)。Co Mi SS的ROC曲线下面积(AUC)为0.846,最佳诊断界值为5.5分,其敏感度为88.2%,特异度为66.7%。结论 Co Mi SS方法简易,可操作性强,以Co Mi SS≥12分作为CMPA早期识别标准易造成漏诊。在我国是否将血便等因素纳入评分或将分值取整以Co Mi SS≥6分作为早期识别标准,仍需进一步大样本研究。     

牛奶蛋白过敏婴儿的配方奶使用指南:澳大利亚专家组共识

概要 3种婴儿配方奶(豆基配方、深度水解配方和氨基酸配方)可用于治疗牛奶蛋白过敏症. 应根据过敏综合征选择配方奶. 深度水解配方奶首选用于治疗6个月以下婴儿的速发性牛奶蛋白过敏(非全身过敏反应)、食物蛋白诱发的小肠结肠炎综合征、特应性湿疹、胃肠道综合征和食物蛋白诱发的直肠结肠炎.豆基配方奶首选用于治疗6个月以上婴儿的速发性食物反应、胃肠道综合征或不伴生长发育障碍的特异性皮炎.     

婴儿牛奶蛋白过敏的诊断

<正>婴儿期最常见的过敏性疾病是食物过敏,由于牛奶蛋白是婴儿期主要的食物蛋白来源,所以婴儿期食物过敏以牛奶蛋白过敏(cow's milk allergy,CMA)最为常见。牛奶蛋白过敏可涉及全身各个系统,并以消化系统症状和皮肤症状为最主要表现。如:呕吐、反流、腹泻、便血、肠绞痛、湿疹、荨麻疹等。这些症状均为非特异性。单从临床症状判断是否为食物过敏有一定的困难,需要结合辅助检查进行综合分析。本文探讨婴儿牛奶蛋白过敏的诊断及鉴别诊断。     

人乳喂养与牛奶蛋白过敏

人乳比常规婴儿配方营养、健康。虽然缺乏强有力的证据显示人乳喂养可预防特应性疾病,但因人乳喂养对婴儿的营养与免疫作用,人乳对婴儿心理发育的益处和其他优点是其他任何食物无可替代的。因此,各国指南仍然建议所有婴儿包括有特应性疾病家族史的婴儿应纯人乳喂养至4~6月龄。     

牛奶蛋白过敏及耐受不良

1901年Hamberger首先以牛奶蛋白耐受不良解释婴儿症状,随后出现了第1例喂牛奶后发生过敏性休克的报告,所以对牛奶过敏是在本世纪初才开始认识的。但直到1963年Goldman等建立临床标准后,牛奶过敏的诊断始广泛应用。美国约有1%婴儿对牛奶过敏,以色列估计为0.5%,故并不少见。57%发生于生后第1个月的婴儿。牛奶过敏与耐受不良系指同一疾病,有些国家用牛奶耐受不良     

Indices of protein metabolism in term infants fed human milk, whey-predominant formula, or cow's milk formula

Relationships between intakes of amino acids and total nitrogen, and blood indices of protein utilization were studied in 37 term infants fed either human milk, whey-predominant formula, or cow's milk formula as the sole nutritional source for 8 weeks. Biochemical analyses of two-hour fasting blood samples, and intakes calculated using three-day dietary records and direct analyses of milk samples were used to evaluate these relationships. Intakes of total nitrogen were positively correlated with plasma valine, leucine, isoleucine, phenylalanine, and serum urea nitrogen concentrations (r = .46 to .62, P less than .01 to .001). Intakes of the four amino acids whose plasma concentrations were positively correlated with total nitrogen intakes plus four additional amino acids (threonine, tyrosine, histidine, and methionine) were correlated with their respective plasma concentrations (r = .41 to .74, P less than .01 to .001). These relationships have not been previously described in term infants. Compared with values in infants fed human milk, plasma concentrations of valine, phenylalanine, methionine, and serum urea nitrogen were elevated with whey-predominant formula and cow's milk formula feeding. Values for four additional amino acids (threonine, lysine, leucine, and isoleucine) were elevated with whey-predominant formula feeding. Data indicate that altering the whey-to-casein ratio and, thus, the amino acid pattern of formulas will not achieve the desired blood indices characteristic of human milk feeding without a reduction in the total nitrogen content of formulas.     

Biotin and carnitine deficiency due to hypoallergenic formula nutrition in infants with milk allergy

Amino acid formulas and hydrolyzed formulas given to infants in Japan with milk allergies theoretically contain little, if any, biotin and carnitine. We assessed biotin and carnitine insufficiency in six infants with milk allergy who were fed amino acid formulas and/or hydrolyzed formulas, by measuring urine 3‐hydroxyisovaleric acid (3‐HIA) and serum free carnitine (C0), respectively. All patients presented with elevated urine 3‐HIA and lowered serum C0 compared with post‐menstrual age‐matched infants who were fed breast milk or standard infant formulas. Supplementation with biotin and l ‐carnitine immediately improved the insufficiency. Care should be taken to avoid biotin and carnitine deficiency in allergic infants fed amino acid or hydrolyzed formulas.     

Incidence and symptoms of cow's milk protein intolerance following acute gastroenteritis in young infants. Effect of a hypoallergenic diet

In a prospective randomized study we investigated in 28 mainly bottle-fed infants younger than 60 days whether in acute gastroenteritis a hypoallergenic formula could prevent the development of cow's milk protein intolerance. Group 1 (14 infants) was fed with a formula adapted to human milk, Group 2 (14 infants) got a semi-elementary formula (Alfaré). After 3 months group II was exposed to cow's milk protein with a standardized challenge and the incidence of CMPI in both groups was calculated. All cases with the acute form of CMPI occurred in group II (5/12) whereas in group I only one infant suffered from the protracted mild form of the disease. Inspite of the relatively small number of probands we conclude from our results that in infants who are not totally breast-fed in the post-enteritic period feeding with a formula adapted to human milk is preferable to hypoallergenic semi-elementary preparations. An allergen free period of 3 months seems to induce symptoms of cow's milk intolerance, probably as a booster-effect to early sensibilisation.     

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.     

A prospective study of cow's milk allergy in exclusively breast-fed infants. Incidence, pathogenetic role of early inadvertent exposure to cow's milk formula, and characterization of bovine milk protein in human milk

A cohort of 1,749 newborns in the municipality of Odense were followed prospectively for the development of cow's milk allergy (CMA) during their first year of life. Altogether 39 fulfilled the criteria for CMA (2.2%). Out of the 39 infants, 17 developed symptoms of CMA during breast-feeding, in all cases before the age of 3 months. Nine of these were solely breast-fed at the time of diagnosis, giving a one year incidence of CMA in exclusively breast-fed infants of 0.5% (9/1,749) in a study population with a frequency of exclusive breast-feeding of 52% at 3 months of age. None of the infants had signs of CMA in the neonatal period. Review of records from the newborn nursery revealed that all 9 infants had been exposed to cow's milk formula in amounts corresponding to approximately 0.4-3.0 g of beta-lactoglobulin (BLG) during the first three days of life. Human milk samples were analyzed by enzyme-linked immunosorbent assay (ELISA) for the content of bovine BLG. Detectable amounts (0.5-45 ng/ml) were found in 3/9 samples of human milk against which the infants reacted clinically. Analysis of the size distribution by high pressure liquid gel permeation chromatography in combination with ELISA indicated a molecular weight of BLG corresponding to that of monomeric BLG (18 kD). Possibly early inadvertent and occasional exposure to cow's milk proteins may initiate sensitization in predisposed neonates. Subsequent exposure to minute amounts of bovine milk proteins in human milk may act as booster doses eliciting allergic reactions.