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生命最初 5 年的麸质摄入量与发生于高危儿童的乳糜泻自身免疫和乳糜泻的相关性。

Association of Gluten Intake During the First 5 Years of Life With Incidence of Celiac Disease Autoimmunity and Celiac Disease Among Children at Increased Risk.

机构信息

Department of Clinical Sciences, Lund University, Malmö, Sweden.

Health Informatics Institute, Department of Pediatrics, Morsani College of Medicine, University of South Florida, Tampa.

出版信息

JAMA. 2019 Aug 13;322(6):514-523. doi: 10.1001/jama.2019.10329.

Abstract

IMPORTANCE

High gluten intake during childhood may confer risk of celiac disease.

OBJECTIVES

To investigate if the amount of gluten intake is associated with celiac disease autoimmunity and celiac disease in genetically at-risk children.

DESIGN, SETTING, AND PARTICIPANTS: The participants in The Environmental Determinants of Diabetes in the Young (TEDDY), a prospective observational birth cohort study designed to identify environmental triggers of type 1 diabetes and celiac disease, were followed up at 6 clinical centers in Finland, Germany, Sweden, and the United States. Between 2004 and 2010, 8676 newborns carrying HLA antigen genotypes associated with type 1 diabetes and celiac disease were enrolled. Screening for celiac disease with tissue transglutaminase autoantibodies was performed annually in 6757 children from the age of 2 years. Data on gluten intake were available in 6605 children (98%) by September 30, 2017.

EXPOSURES

Gluten intake was estimated from 3-day food records collected at ages 6, 9, and 12 months and biannually thereafter until the age of 5 years.

MAIN OUTCOMES AND MEASURES

The primary outcome was celiac disease autoimmunity, defined as positive tissue transglutaminase autoantibodies found in 2 consecutive serum samples. The secondary outcome was celiac disease confirmed by intestinal biopsy or persistently high tissue transglutaminase autoantibody levels.

RESULTS

Of the 6605 children (49% females; median follow-up: 9.0 years [interquartile range, 8.0-10.0 years]), 1216 (18%) developed celiac disease autoimmunity and 447 (7%) developed celiac disease. The incidence for both outcomes peaked at the age of 2 to 3 years. Daily gluten intake was associated with higher risk of celiac disease autoimmunity for every 1-g/d increase in gluten consumption (hazard ratio [HR], 1.30 [95% CI, 1.22-1.38]; absolute risk by the age of 3 years if the reference amount of gluten was consumed, 28.1%; absolute risk if gluten intake was 1-g/d higher than the reference amount, 34.2%; absolute risk difference, 6.1% [95% CI, 4.5%-7.7%]). Daily gluten intake was associated with higher risk of celiac disease for every 1-g/d increase in gluten consumption (HR, 1.50 [95% CI, 1.35-1.66]; absolute risk by age of 3 years if the reference amount of gluten was consumed, 20.7%; absolute risk if gluten intake was 1-g/d higher than the reference amount, 27.9%; absolute risk difference, 7.2% [95% CI, 6.1%-8.3%]).

CONCLUSIONS AND RELEVANCE

Higher gluten intake during the first 5 years of life was associated with increased risk of celiac disease autoimmunity and celiac disease among genetically predisposed children.

摘要

重要性

儿童时期摄入大量的面筋可能会增加患乳糜泻的风险。

目的

研究儿童时期摄入的面筋量是否与乳糜泻自身免疫和遗传易感儿童的乳糜泻有关。

设计、环境和参与者:本研究参与者来自于环境决定糖尿病易感性的年轻人(TEDDY),这是一项前瞻性观察性出生队列研究,旨在确定 1 型糖尿病和乳糜泻的环境触发因素。在芬兰、德国、瑞典和美国的 6 个临床中心进行了随访。2004 年至 2010 年间,共招募了 8676 名携带与 1 型糖尿病和乳糜泻相关的 HLA 抗原基因型的新生儿。在 2 岁的 6757 名儿童中,每年通过组织转谷氨酰胺酶自身抗体进行乳糜泻筛查。截至 2017 年 9 月 30 日,6605 名儿童(98%)可提供关于面筋摄入量的资料。

暴露

在 6 个月、9 个月和 12 个月以及此后每 2 个月的 3 天食物记录中估计面筋摄入量,直到 5 岁。

主要结果和测量

主要结局是乳糜泻自身免疫,定义为在 2 份连续血清样本中发现阳性组织转谷氨酰胺酶自身抗体。次要结局是通过肠活检或持续高组织转谷氨酰胺酶自身抗体水平证实的乳糜泻。

结果

在 6605 名儿童(49%为女性;中位随访时间:9.0 年[四分位间距,8.0-10.0 年])中,1216 名(18%)发生乳糜泻自身免疫,447 名(7%)发生乳糜泻。这两种结果的发病高峰都在 2 至 3 岁。与每天摄入的面筋量相比,每增加 1g/d 面筋摄入量,乳糜泻自身免疫的风险就会增加(风险比[HR],1.30[95%置信区间,1.22-1.38];如果参考量的面筋被消耗,3 岁时的绝对风险为 28.1%;如果面筋摄入量比参考量高 1g/d,绝对风险为 34.2%;绝对风险差异,6.1%[95%置信区间,4.5%-7.7%])。与每天摄入的面筋量相比,每增加 1g/d 面筋摄入量,乳糜泻的风险就会增加(HR,1.50[95%置信区间,1.35-1.66];如果参考量的面筋被消耗,3 岁时的绝对风险为 20.7%;如果面筋摄入量比参考量高 1g/d,绝对风险为 27.9%;绝对风险差异,7.2%[95%置信区间,6.1%-8.3%])。

结论和相关性

在生命的头 5 年中,摄入更多的面筋与遗传易感儿童中乳糜泻自身免疫和乳糜泻的风险增加有关。

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