Background & Aims

Feeding during the first months of life might affect risk for celiac disease. Individuals with celiac disease or type 1 diabetes have been reported to have high titers of antibodies against cow’s milk proteins. Avoidance of cow’s milk−based formula for infants with genetic susceptibility for type 1 diabetes reduced the cumulative incidence of diabetes-associated autoantibodies. We performed a randomized controlled trial in the same population to study whether weaning to an extensively hydrolyzed formula reduced the risk of celiac disease autoimmunity or celiac disease.

Methods

We performed a double-blind controlled trial of 230 infants with HLA-defined predisposition to type 1 diabetes and at least 1 family member with type 1 diabetes. The infants were randomly assigned to groups fed a casein hydrolysate formula (n = 113) or a conventional formula (control, n = 117) whenever breast milk was not available during the first 6−8 months of life. Serum samples were collected over a median time period of 10 years and analyzed for antibodies to tissue transglutaminase (anti-TG2A) using a radiobinding assay, to endomysium using an immunofluorescence assay, and antibodies to a deamidated gliadine peptide using an immunofluorometry assay. Duodenal biopsies were collected if levels of anti-TG2A exceeded 20 relative units. Cow’s milk antibodies were measured during the first 2 years of life.

Results

Of the 189 participants analyzed for anti-TG2A, 25 (13.2%) tested positive. Of the 230 study participants observed, 10 (4.3%) were diagnosed with celiac disease. We did not find any significant differences at the cumulative incidence of anti-TG2A positivity (hazard ratio, 1.14; 95% confidence interval, 0.51−2.54) or celiac disease (hazard ratio, 4.13; 95% confidence interval, 0.81−21.02) between the casein hydrolysate and cow’s milk groups. Children who developed celiac disease had increased titers of cow’s milk antibodies before the appearance of anti-TG2A or celiac disease.

Conclusions

In a randomized controlled trial of 230 infants with genetic risk factors for celiac disease, we did not find evidence that weaning to a diet of extensively hydrolyzed formula compared with cow’s milk−based formula would decrease the risk for celiac disease later in life. Increased titers of cow's milk antibody before anti-TG2A and celiac disease indicates that subjects with celiac disease might have increased intestinal permeability in early life. ClinicalTrials.gov Number: NCT00570102.

中文翻译：

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避免以牛奶为基础的高危婴儿配方奶粉不会减少腹腔疾病的发展：一项随机对照试验

背景与目标

在生命的头几个月中进食可能会影响乳糜泻的风险。据报道患有乳糜泻或1型糖尿病的人具有高滴度的抗牛奶蛋白抗体。对具有1型糖尿病遗传易感性的婴儿避免使用基于牛奶的配方奶可降低与糖尿病相关的自身抗体的累积发生率。我们在同一人群中进行了一项随机对照试验，以研究断奶至广泛水解的配方奶粉是否可以降低腹腔疾病自身免疫或腹腔疾病的风险。

方法

我们进行了一项230名HLA定义的1型糖尿病易感性婴儿和至少1名1型糖尿病家庭成员的双盲对照试验。当婴儿在出生后的头6-8个月内没有乳汁时，将其随机分配为喂酪蛋白水解物配方食品（n = 113）或常规配方食品（对照组，n = 117）的组。在10年的中值时间内收集血清样品，并使用放射结合测定法分析针对组织转谷氨酰胺酶（anti-TG2A）的抗体，使用免疫荧光测定法分析针对内膜的抗体，并使用免疫荧光测定法分析针对脱酰胺化的gliadine肽的抗体。如果抗TG2A的水平超过20个相对单位，则收集十二指肠活组织检查。在生命的最初2年中测量了牛奶抗体。

结果

在分析抗TG2A的189位参与者中，有25位（13.2％）测试呈阳性。在观察的230名研究参与者中，有10名（4.3％）被诊断患有乳糜泻。在两者之间的抗TG2A阳性率（危险比，1.14； 95％置信区间，0.51-2.54）或乳糜泻（危险比，4.13； 95％置信区间，0.81-21-22）之间的累积发生率方面，我们没有发现任何显着差异。酪蛋白水解物和牛奶组。发生乳糜泻的儿童在出现抗TG2A或乳糜泻之前，其牛奶抗体的滴度增加。

结论

在一项对230名患有乳糜泻遗传风险因素的婴儿进行的随机对照试验中，我们没有发现证据表明，断奶与母乳喂养的配方奶相比，广泛水解的配方奶饮食可以降低以后发生乳糜泻的风险。抗TG2A和乳糜泻之前的牛乳抗体滴度增加表明，患有乳糜泻的受试者可能在早期生活中肠通透性增加。ClinicalTrials.gov编号：NCT00570102。