Can early introduction of gluten reduce risk of celiac disease?

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doi:doi: 10.12788/jfp.0447

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Can early introduction of gluten reduce risk of celiac disease?

J Fam Pract. 2022 July;71(6):E4-E6 | doi: 10.12788/jfp.0447

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References

1. Logan K, Perkin MR, Marrs T, et al. Early gluten introduction and celiac disease in the EAT Study: a prespecified analysis of the EAT randomized clinical trial. JAMA Pediatr. 2020;174:1041-1047. doi: 10.1001/jamapediatrics.2020.2893

2. King JA, Jeong J, Underwood FE, et al. Incidence of celiac disease is increasing over time: a systematic review and meta-analysis. Am J Gastroenterol. 2020;115:507-525. doi: 10.14309/ajg.0000000000000523

3. Rubio-Tapia A, Hill ID, Kelly CP, et al; American College of Gastroenterology. ACG clinical guidelines: diagnosis and management of celiac disease. Am J Gastroenterol. 2013;108:656-676; quiz 677. doi: 10.1038/ajg.2013.79

4. Husby S, Koletzko S, Korponay-Szabó I, et al. European Society Paediatric Gastroenterology, Hepatology and Nutrition guidelines for diagnosing coeliac disease 2020. J Pediatr Gastroenterol Nutr. 2020;70:141-156. doi: 10.1097/MPG.0000000000002497

5. Vriezinga SL, Auricchio R, Bravi E, et al. Randomized feeding intervention in infants at high risk for celiac disease. N Engl J Med. 2014;371:1304-1315. doi: 10.1056/NEJMoa1404172

6. Beyerlein A, Chmiel R, Hummel S, et al. Timing of gluten introduction and islet autoimmunity in young children: updated results from the BABYDIET study. Diabetes Care. 2014;37:e194-e195. doi: 10.2337/dc14-1208

7. Lionetti E, Castellaneta S, Francavilla R, et al; SIGENP (Italian Society of Pediatric Gastroenterology, Hepatology, and Nutrition) Working Group on Weaning and CD Risk. Introduction of gluten, HLA status, and the risk of celiac disease in children. N Engl J Med. 2014;371:1295-1303. doi: 10.1056/NEJMoa1400697

8. Pinto-Sánchez MI, Verdu EF, Liu E, et al. Gluten introduction to infant feeding and risk of celiac disease: systematic review and meta-analysis. J Pediatr. 2016;168:132-143.e3. doi: 10.1016/j.jpeds.2015.09.032

9. US Department of Agriculture, US Department of Health and Human Services. Dietary Guidelines for Americans, 2020-2025. 9th ed. December 2020. Accessed June 8, 2022. www.dietaryguidelines.gov/sites/default/files/2021-03/Dietary_Guidelines_for_Americans-2020-2025.pdf

10. NHS. Food allergies in babies and young children. Last reviewed November 5, 2021. Accessed June 8, 2022. www.nhs.uk/conditions/baby/weaning-and-feeding/food-allergies-in-babies-and-young-children/

11. Szajewska H, Shamir R, Mearin L, et al. Gluten introduction and the risk of coeliac disease: a position paper by the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition. J Pediatr Gastroenterol Nutr. 2016;62:507-513. doi: 10.1097/MPG.0000000000001105

12. Perkin MR, Logan K, Marrs T, et al; EAT Study Team. Enquiring About Tolerance (EAT) study: feasibility of an early allergenic food introduction regimen. J Allergy Clin Immunol. 2016;137:1477-1486.e8. doi: 10.1016/j.jaci.2015.12.1322

13. Perkin MR, Logan K, Tseng A, et al; EAT Study Team. Randomized trial of introduction of allergenic foods in breast-fed infants. N Engl J Med. 2016;374:1733-1743. doi: 10.1056/NEJMoa1514210

Families completed monthly questionnaires on infant gluten intake and symptoms (eg, gastrointestinal, fatigue) through age 1 year, and then every 3 months through age 3 years. All children were tested for anti-transglutaminase type 2 (anti-TG2) antibodies at age 3 years as a screen for CD. Children with antibody levels > 20 IU/L were referred to independent gastroenterologists for further evaluation, which could include HLA (DQ-2/DQ-8) testing and biopsy in accordance with current European diagnostic guidelines.⁴

Introducing gluten as a complement to breast milk or infant formula from age 4 months may reduce the risk of celiac disease at age 3 years.

In an intention-to-treat analysis for the primary outcome, 595 children in the SIG (91.4%) and 567 in the EIG (87.0%) were included. Between ages 4 and 6 months, the mean (SD) quantity of gluten consumed in the SIG was 0.49 (1.40) g/wk; in the EIG, the mean quantity was 2.66 (1.85) g/wk (P < .001). At age 3 years, of a total of 1004 children tested for anti-TG2 antibodies, 9 had anti-TG2 levels requiring referral (7 in the SIG and 2 in the EIG). A diagnosis of CD was confirmed in 7 of 516 children in the SIG (1.4%) vs none of the 488 children in the EIG (P = .02). Using bootstrap resampling, the risk difference between the groups was 1.4% (95% CI, 0.6%-2.6%).

WHAT’S NEW

Findings have potential to change nutritional guidance

This study demonstrated that introduction of age-appropriate portions of gluten-containing products at age 4 months, in addition to breast milk, may reduce the risk of CD at 3 years in children at average risk. This finding has the potential to change anticipatory guidance given to parents regarding infant nutrition recommendations.

CAVEATS

More studies needed to confirm prevention vs delay of CD

The homogeneous study population may limit generalizability. Infants in this study were from England and Wales (84.3% were White), born at term, and were exclusively breastfed until age 13 weeks. Further studies are required to determine whether these findings can be applied to infants who are no longer breastfeeding, are more racially diverse, or are preterm in gestational age at birth. Additionally, the study followed the participants only until age 3 years. Given that the onset of CD after this age is likely, further research is needed to support that CD is truly prevented rather than delayed.

CHALLENGES TO IMPLEMENTATION

Guidance on allergen introduction may be unclear

The EAT Study protocol required parents in the EIG to sequentially introduce a minimum amount of the 6 allergenic foods specified. Only 42% of the EIG cohort reported adherence to the protocol.¹² It is unclear how important this specific regimen is to the study results and whether introduction of all 6 allergenic foods simultaneously modifies the immune response to gluten. Therefore, there may be challenges to implementation if physicians do not know how to provide anticipatory guidance on the appropriate steps for allergen introduction.