Department of Clinical Sciences, Lund University, Malmö, Sweden;
Pediatrics Epidemiology Center, Department of Pediatrics, Morsani College of Medicine, University of South Florida, Tampa, Florida;
Pediatrics. 2015 Feb;135(2):239-45. doi: 10.1542/peds.2014-1787. Epub 2015 Jan 19.
The goal of this study was to determine whether age at introduction to gluten was associated with risk for celiac disease (CD) in genetically predisposed children.
TEDDY (The Environmental Determinants of Diabetes in the Young) is a prospective birth cohort study. Newborn infants (N = 6436) screened for high-risk HLA-genotypes for CD were followed up in Finland, Germany, Sweden, and the United States. Information about infant feeding was collected at clinical visits every third month. The first outcome was persistent positive for tissue transglutaminase autoantibodies (tTGA), the marker for CD. The second outcome was CD, defined as either a diagnosis based on intestinal biopsy results or on persistently high levels of tTGA.
Swedish children were introduced to gluten earlier (median: 21.7 weeks) compared with children from Finland (median: 26.1 weeks), Germany, and the United States (both median: 30.4 weeks) (P < .0001). During a median follow-up of 5.0 years (range: 1.7-8.8 years), 773 (12%) children developed tTGA and 307 (5%) developed CD. Swedish children were at increased risk for tTGA (hazard ratio: 1.74 [95% CI: 1.47-2.06]) and CD (hazard ratio: 1.76 [95% CI: 1.34-2.24]) compared with US children, respectively (P < .0001).Gluten introduction before 17 weeks or later than 26 weeks was not associated with increased risk for tTGA or CD, adjusted for country, HLA, gender, and family history of CD, neither in the overall analysis nor on a country-level comparison.
In TEDDY, the time to first introduction to gluten introduction was not an independent risk factor for developing CD.
本研究旨在确定在具有遗传易感性的儿童中,引入 gluten 的年龄是否与乳糜泻(celiac disease,CD)的风险相关。
TEDDY(青少年糖尿病的环境决定因素)是一项前瞻性出生队列研究。对筛查出 CD 高危 HLA 基因型的新生儿(N=6436)在芬兰、德国、瑞典和美国进行了随访。在临床就诊时,每三个月收集一次婴儿喂养信息。第一个结局是组织转谷氨酰胺酶自身抗体(tissue transglutaminase autoantibodies,tTGA)持续阳性,这是 CD 的标志物。第二个结局是 CD,定义为基于肠道活检结果或持续高水平 tTGA 的诊断。
与芬兰、德国和美国的儿童相比,瑞典儿童引入 gluten 的时间更早(中位数:21.7 周)(P<0.0001)。在中位数为 5.0 年(范围:1.7-8.8 年)的随访期间,773 名(12%)儿童出现 tTGA,307 名(5%)儿童出现 CD。与美国儿童相比,瑞典儿童患 tTGA(风险比:1.74[95%可信区间:1.47-2.06])和 CD(风险比:1.76[95%可信区间:1.34-2.24])的风险增加(P<0.0001)。调整国家、HLA、性别和 CD 家族史后,在总体分析和国家层面比较中,17 周前或 26 周后引入 gluten 与 tTGA 或 CD 风险增加无关。
在 TEDDY 中,首次引入 gluten 的时间不是发生 CD 的独立危险因素。