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Early Gluten Exposure and Risk for Celiac Disease

Timing of introduction of gluten to diets of high-risk infants is associated with celiac disease.

To assess whether the timing of introduction of gluten to infants’ diets influences subsequent onset of celiac disease autoimmunity (CDA), investigators in Colorado prospectively followed 1560 high-risk children (mean follow-up, 4.8 years). Children at high risk for CD had either human leukocyte antigen (HLA)-DR3 or -DR4 alleles or a first-degree relative with type 1 diabetes (because these same alleles confer an increased risk for type 1 diabetes). Onset of CDA was defined as two or more consecutive tests that showed positive antibodies for tissue transglutaminase (tTG). Children were tested at birth, 9, 15, and 24 months, and annually thereafter. Clinical evaluation was conducted after two positive tTG tests. No dietary advice was provided to families.

Of the 51 children who developed CDA, 34 underwent small-bowel biopsies (25 were CDA-positive). The mean age at first positive tTG antibody test was 4.7 years. Three CDA-positive children (6%) were exposed to wheat, barley, and rye (gluten foods) by 3 months of age; 12 (23%) were exposed at 4 to 6 months, and 36 (71%) at or after age 7 months. Among HLA-DR3–positive children, introduction of gluten foods by age 3 months was associated with a fivefold increased risk for CDA compared with exposure at age 4 to 6 months. Exposure at or after age 7 months was associated with a slightly increased risk for CDA compared with exposure at 4 to 6 months. CDA risk was not influenced by breast-feeding duration or age at exposure to oats, rice, or cow’s milk. In analyses limited to children with the highest risk for celiac disease (HLA-DR3–positive), children exposed to gluten foods during the first 3 months of life had a 40% risk for CDA by age 5.5 years.

Comment: This report is the second by these investigators to show an association between early introduction of certain nutrients and subsequent autoimmunity in high-risk populations (see JW Pediatr Adolesc Med Nov 24 2003). We should caution families with a history of type 1 diabetes or celiac disease about early exposure to wheat, barley, or rye, as is recommended by the American Academy of Pediatrics. I would not specifically expose at-risk infants to gluten at age 4 to 6 months based solely on these data, but we should watch this literature carefully.

— F. Bruder Stapleton, MD

Published in Journal Watch Pediatrics and Adolescent Medicine July 25, 2005

Citation(s):

Norris JM et al. Risk of celiac disease autoimmunity and timing of gluten introduction in the diet of infants at increased risk of disease. JAMA 2005 May 18; 293:2343-51.

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