Andrén Aronsson Carin, Lee Hye-Seung, Koletzko Sibylle, Uusitalo Ulla, Yang Jimin, Virtanen Suvi M, Liu Edwin, Lernmark Åke, Norris Jill M, Agardh Daniel
Department of Clinical Sciences, Lund University, Skåne University Hospital, Malmö, Sweden.
Health Informatics Institute, Morsani College of Medicine, University of South Florida, Tampa, Florida.
Clin Gastroenterol Hepatol. 2016 Mar;14(3):403-409.e3. doi: 10.1016/j.cgh.2015.09.030. Epub 2015 Nov 25.
BACKGROUND & AIMS: Early nutrition may affect the risk of celiac disease. We investigated whether amount of gluten in diet until 2 years of age increases risk for celiac disease.
We performed a 1-to-3 nested case-control study of 146 cases, resulting in 436 case-control pairs matched for sex, birth year, and HLA genotype generated from Swedish children at genetic risk for celiac disease. Newborns were annually screened for tissue transglutaminase autoantibodies (tTGA). If tested tTGA positive, time point of seroconversion was determined from frozen serum samples taken every 3 months. Celiac disease was confirmed by intestinal biopsies. Gluten intake was calculated from 3-day food records collected at ages 9, 12, 18 and 24 months. Odds ratios (OR) were calculated through conditional logistic regression.
Breastfeeding duration (median, 32 wk) and age at first introduction to gluten (median, 22 wk) did not differ between cases and tTGA-negative controls. At the visit before tTGA seroconversion, cases reported a larger intake of gluten than controls (OR, 1.28; 95% confidence interval [CI], 1.13-1.46; P = .0002). More cases than controls were found in the upper third tertile (ie, >5.0 g/d) before they tested positive for tTGA seroconversion than controls (OR, 2.65; 95% CI, 1.70-4.13; P < .0001). This finding was similar in children homozygous for DR3-DQ2 (OR, 3.19; 95% CI, 1.61-6.30; P = .001), heterozygous for DR3-DQ2 (OR, 2.24; 95% CI, 1.08-4.62; P = .030), and for children not carrying DR3-DQ2 (OR, 2.43; 95% CI, 0.90-6.54; P = .079).
The amount of gluten consumed until 2 years of age increases the risk of celiac disease at least 2-fold in genetically susceptible children. These findings may be taken into account for future infant feeding recommendations.
早期营养可能会影响乳糜泻的患病风险。我们研究了2岁前饮食中的麸质含量是否会增加患乳糜泻的风险。
我们对146例病例进行了一项1:3巢式病例对照研究,最终形成了436对病例对照,这些对照在性别、出生年份和HLA基因型方面与有乳糜泻遗传风险的瑞典儿童相匹配。每年对新生儿进行组织转谷氨酰胺酶自身抗体(tTGA)筛查。如果检测到tTGA呈阳性,则从每3个月采集的冷冻血清样本中确定血清转化的时间点。通过肠道活检确诊乳糜泻。根据9、12、18和24个月时收集的3天饮食记录计算麸质摄入量。通过条件逻辑回归计算比值比(OR)。
病例组和tTGA阴性对照组在母乳喂养持续时间(中位数,32周)和首次引入麸质的年龄(中位数,22周)方面没有差异。在tTGA血清转化前的那次就诊时,病例组报告的麸质摄入量高于对照组(OR,1.28;95%置信区间[CI],1.13 - 1.46;P = 0.0002)。在tTGA血清转化检测呈阳性之前,病例组中处于上三分位数(即>5.0 g/d)的人数比对照组更多(OR,2.65;95% CI,1.70 - 4.13;P < 0.0001)。在DR3 - DQ2纯合子儿童(OR,3.19;95% CI,1.61 - 6.30;P = 0.001)、DR3 - DQ2杂合子儿童(OR,2.24;95% CI,1.08 - 4.62;P = 0.030)以及未携带DR3 - DQ2的儿童中(OR,2.43;95% CI,0.90 - 6.54;P = 0.079),这一发现是相似的。
在2岁前摄入的麸质量会使遗传易感性儿童患乳糜泻的风险至少增加2倍。在未来制定婴儿喂养建议时可考虑这些发现。