Systematic Review: Early Infant Feeding and the Prevention of Coeliac Disease

H. Szajewska; A. Chmielewska; M. Pieścik-Lech; A. Ivarsson; S. Kolacek; S. Koletzko; M. L. Mearin; R. Shamir; R. Auricchio; R. Troncone


Aliment Pharmacol Ther. 2012;36(7):607-618. 

In This Article

Abstract and Introduction


Background PREVENTCD, Prevent Coeliac Disease, is an international project investigating the hypothesis of possible induction of tolerance to gluten in genetically predisposed children through introducing small quantities of gluten during the period of breastfeeding.
Aim To summarise current knowledge on the possible relationship between early feeding practices and the risk of coeliac disease (CD).
Methods The Cochrane Library, MEDLINE, and EMBASE databases were searched in May 2011, and the search was updated in January 2012, and again in July 2012.
Results Breastfeeding (BF) and CD: some studies show a protective effect of BF, while others show no effect. No studies have shown a long-term preventive effect. BF at the time of gluten introduction and CD: Results from a meta-analysis of five observational case-control studies suggest that BF at gluten introduction is associated with a lower risk of CD compared with formula feeding. It is unclear whether BF provides a permanent protection or only delays the onset of CD. Timing of gluten introduction: The data suggest that both early (≤4 months) and late (≥7 months) introduction of gluten may increase the risk of CD. Amount of gluten at weaning (and later) and CD: One incident case-referent study documented that the introduction of gluten in large amounts compared with small or medium amounts increased the risk of CD.
Conclusions In the absence of clear evidence, in order to decrease the risk of later coeliac disease, it is reasonable to avoid both early (<4 months) and late (≥7 months) introduction of gluten, and to introduce gluten while the infant is still being breastfed. Future studies may clarify the remaining uncertainties.


Coeliac disease (CD) has been recently defined by the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) as 'an immune-mediated systemic disorder elicited by gluten and related prolamines in genetically susceptible individuals and characterized by the presence of a variable combination of gluten-dependent clinical manifestations, CD-specific antibodies, HLA-DQ2 or HLA-DQ8 haplotypes, and enteropathy. CD-specific antibodies comprise autoantibodies against TG2 (anti-TG2), including endomysial antibodies (EMA), and antibodies against deamidated forms of gliadin peptides (DGP)'.[1]

The incidence of CD is as high as 0.5–1.6% in the general population in Europe and North America.[2] Higher rates are reported in first-degree relatives of patients with CD, patients with autoimmune diseases such as type 1 diabetes or autoimmune thyroid disease, patients with some chromosomal aberration disorders (e.g. Down syndrome, Turner syndrome, Williams syndrome), and patients with selective IgA deficiency. The course of CD may be symptomatic with the occurrence of gastrointestinal and nongastrointestinal symptoms. However, CD also may develop as an asymptomatic disease.[1] A lifelong, gluten-free diet introduced only when a conclusive diagnosis has been made is the recommended treatment.

Recently, key stakeholders representing a wide range of knowledge related to CD concluded that the option of primary prevention should be fully explored, which requires combined epidemiological, clinical and basic scientific research efforts. In particular, a great deal of attention should be focused on the relationship between early nutrition and later development of CD, particularly on the timing and circumstances of gluten introduction.[3]

PREVENTCD, Prevent Coeliac Disease (, is an international project, sponsored by the European Union 6th Framework Programme. The aim of this project is to investigate the hypothesis of possible induction of tolerance to gluten in genetically predisposed children through the introduction of small quantities of gluten during the period of breastfeeding. The pivotal objective of the project is to significantly reduce the number of people suffering from CD in Europe by developing primary prevention strategies. To achieve this, PREVENTCD involved the following areas of research in relation to CD development: (i) infant feeding, especially breastfeeding and gluten introduction (based on a randomised, double-blind, controlled trial involving high-risk infants and the Food Frequency Questionnaire as well as a Swedish CD screening study among 12-year-old children from two population cohorts that differ with respect to infant feeding); (ii) immunological response to gluten introduction; and (iii) genetic factors (both HLA and non-HLA alleles). A detailed description of each study field has been published separately.[4–7] Revision of the current European guidelines for early nutrition to prevent CD is the final objective of PREVENTCD. This, however, can only be achieved when all data are analysed. The analysis of all data will be feasible only after 2013 when all infants recruited into the intervention study will have reached 3 years of age, the code will have been broken, and thus, the study unblinded.

The purpose of this report developed by PREVENTCD investigators is to summarise current knowledge concerning the possible relationship between early feeding practices and the risk of developing CD. In particular, a systematic review was designed to answer the following clinical questions grouped into four categories important for making future recommendations:

  1. Breastfeeding (BF) and CD (Does any BF reduce the risk of developing CD in early childhood? Is there a difference between any or exclusive BF in regard to risk reduction? Is the duration of BF related to the risk of developing CD?).

  2. BF at the time of gluten introduction and CD (Is gluten consumption while being breastfed important for risk reduction?).

  3. Timing of gluten introduction (Is age of gluten introduction important to the risk of developing CD?).

  4. Amount of gluten at weaning (and later) and CD (Is the amount of gluten ingested an independent risk factor for the development of CD in early childhood? Is there a threshold level of gluten consumption for developing CD in early childhood?).

In addition, we analysed whether manipulation of the intestinal microbiota through the administration of microbial supplements (probiotics) and/or substrates (prebiotics) has an effect on the risk of CD. This was based on recent studies suggesting that aberrant development and maturity of the gut microbiota is among the environmental factors to be associated with CD.[8–11]

An update of this systematic review together with an update of current recommendations is planned immediately after findings from PREVENTCD are available.