Gluten Introduction and the Risk of Coeliac Disease. A Position Paper by the European Society for Paediatric Gastroenterology, Hepatology and Nutrition
Szajewska H, Shamir R, Mearin ML et al. J Paediatr Gastroenterol Nutr (2016)
In 2008, the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) made recommendations regarding gluten introduction to the diet of infants, based on observational data. Following the publication of new evidence, ESPGHAN has revised its 2008 recommendations regarding gluten introduction to the diet of infants and the risk of developing coeliac disease (CD) during childhood.
In 2008, the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) made recommendations regarding gluten introduction to the diet of infants, based on observational data. Following the publication of new evidence, ESPGHAN has revised its 2008 recommendations regarding gluten introduction to the diet of infants and the risk of developing coeliac disease (CD) during childhood.
The 2008 ESPGHAN recommendations centred around avoidance of early (less than 4 months of age) and late (7 or more months of age) gluten introduction and to introduce gluten whilst the infant is still breastfed, as this may reduce not only the risk of CD but also type 1 diabetes and wheat allergy. However, more recently, two randomised controlled trials (RCTs) have examined the effect of age of gluten introduction on the risk of developing coeliac disease autoimmunity (CDA) (defined as positive serology) or CD during childhood in children at genetic risk for CD. A systematic review also evaluated evidence from prospective observational studies published up until February 2015, in this area.
The aim of this paper was to develop recommendations on gluten introduction in infants and the risk of developing CDA or CD during childhood based on the latest evidence. The recommendation development group consisted of experts in the fields of paediatrics and paediatric gastroenterology and nutrition as well as experts in systematic review and GRADE methodology. The first stage of the recommendation development involved listing the clinical questions to answer. Five specific questions, from a systematic review by the PreventCD Study Group, were taken into consideration: 1) Does any breastfeeding compared with no breastfeeding reduce the risk of developing CD?; 2) Does breastfeeding at the time of gluten introduction reduce the risk of developing CD?; 3) Is the age of gluten introduction important to the risk of developing CD? (a number of age groups were assessed); 4) Is the amount of gluten ingested an independent risk factor for the development of CD during early childhood?; and 5) Does the type of cereal at gluten introduction influence CD risk?
Summary of Recommendations
The recommendations are based on the findings in children genetically predisposed to developing CD as the risk of inducing it, through a gluten-containing diet, is only applicable to individuals carrying at least one of the coeliac risk alleles. This applies to 30-40% of the general population in Europe and, to 75-80% of the offspring of families in which at least one first-degree relative is affected by CD. As the genetic risk alleles are usually unknown at time of solid food introduction in infants, the following recommendations are applicable to all infants, although it is accepted these may not be important for approximately two thirds of the population without genetic predisposition.
Breastfeeding and CD
Whilst breastfeeding should be promoted for its well-established health benefits, neither any breastfeeding nor breastfeeding during gluten introduction has been shown to reduce the risk of CD.
Timing of Gluten Introduction
Gluten may be introduced into an infant’s diet anytime between 4-12 completed months of age. The age of gluten introduction in this age range does not seem to influence absolute risk of developing CDA or CD. In children at high risk for CD, earlier gluten introduction (4 vs 6 months or 6 months vs 12 months) is associated with earlier development of CDA and CD, however, the cumulative incidence of each in later childhood is similar.
Type of Gluten
No recommendation can be made regarding the type of gluten used at introduction to the diet.
Amount of Gluten
Neither optimal amounts of gluten at introduction of solid foods to the diet nor the effect of different wheat preparations on the risk of developing CD or CDA have been established. Despite only limited evidence from observational data pointing to an association between the amount of gluten intake and risk of CD, ESPGHAN suggests that consumption of large amounts of gluten should be avoided during the first months after gluten introduction.
Gluten Introduction in children from families with a first-degree relative with CD
Whilst no recommendation was made regarding this point, it remains a matter of debate whether separate recommendations for gluten introduction should be formulated for this group. Whilst current evidence does not support this, it is key that the available literature is highlighted.
As is well established, the prevalence of CD is higher among individuals who have first-degree relatives with CD. HLA-DQ2 homozygosity is associated with a significantly increased risk of CDA and CD amongst first-degree relatives. Data from the PreventCD study and CELIPREV study suggests that very early development of CDA and CD (below 3-5 years of age) affects preferentially children carrying the very high risk CD alleles (HLA-DQ2.5 homozygous), which are found in only 1-2% of the general population but in 10-15% of children with first-degree relatives having CD. These infants may potentially benefit from later gluten introduction.
It could be argued that delaying gluten introduction towards the end of the first year may be considered in all infants from CD families, in order to reduce the risk of early presentation of the disease and the potential adverse effects on growth and development at a young age, despite the fact that delayed introduction may only benefit the 10-15% with high-risk alleles. However, an alternative approach could be to screen (e.g. HLA typing) all children born into families with a first-degree relative with CD to identify infants with high-risk alleles followed by serological testing post gluten-introduction to detect CD before nutritional deficiencies develop. It was recognised that recommendations on screening were beyond the scope of this position paper.
Summary
A number of important questions remain. Further research, specifically multicentre and multinational RCTs, is required to help answer these including the optimal type and amount of gluten to be included at introduction to the diet, as well as, whether delaying gluten introduction for longer than a year would reduce long-term prevalence of CD (the pros and cons of this approach need to be considered). Finally, as primary prevention is not feasible, mass screening remains an open question; specific recommendations on screening strategies for CD in risk groups such as in children with family members affected with CD are required.
Click to read abstract
The aim of this paper was to develop recommendations on gluten introduction in infants and the risk of developing CDA or CD during childhood based on the latest evidence. The recommendation development group consisted of experts in the fields of paediatrics and paediatric gastroenterology and nutrition as well as experts in systematic review and GRADE methodology. The first stage of the recommendation development involved listing the clinical questions to answer. Five specific questions, from a systematic review by the PreventCD Study Group, were taken into consideration: 1) Does any breastfeeding compared with no breastfeeding reduce the risk of developing CD?; 2) Does breastfeeding at the time of gluten introduction reduce the risk of developing CD?; 3) Is the age of gluten introduction important to the risk of developing CD? (a number of age groups were assessed); 4) Is the amount of gluten ingested an independent risk factor for the development of CD during early childhood?; and 5) Does the type of cereal at gluten introduction influence CD risk?
Summary of Recommendations
The recommendations are based on the findings in children genetically predisposed to developing CD as the risk of inducing it, through a gluten-containing diet, is only applicable to individuals carrying at least one of the coeliac risk alleles. This applies to 30-40% of the general population in Europe and, to 75-80% of the offspring of families in which at least one first-degree relative is affected by CD. As the genetic risk alleles are usually unknown at time of solid food introduction in infants, the following recommendations are applicable to all infants, although it is accepted these may not be important for approximately two thirds of the population without genetic predisposition.
Breastfeeding and CD
Whilst breastfeeding should be promoted for its well-established health benefits, neither any breastfeeding nor breastfeeding during gluten introduction has been shown to reduce the risk of CD.
Timing of Gluten Introduction
Gluten may be introduced into an infant’s diet anytime between 4-12 completed months of age. The age of gluten introduction in this age range does not seem to influence absolute risk of developing CDA or CD. In children at high risk for CD, earlier gluten introduction (4 vs 6 months or 6 months vs 12 months) is associated with earlier development of CDA and CD, however, the cumulative incidence of each in later childhood is similar.
Type of Gluten
No recommendation can be made regarding the type of gluten used at introduction to the diet.
Amount of Gluten
Neither optimal amounts of gluten at introduction of solid foods to the diet nor the effect of different wheat preparations on the risk of developing CD or CDA have been established. Despite only limited evidence from observational data pointing to an association between the amount of gluten intake and risk of CD, ESPGHAN suggests that consumption of large amounts of gluten should be avoided during the first months after gluten introduction.
Gluten Introduction in children from families with a first-degree relative with CD
Whilst no recommendation was made regarding this point, it remains a matter of debate whether separate recommendations for gluten introduction should be formulated for this group. Whilst current evidence does not support this, it is key that the available literature is highlighted.
As is well established, the prevalence of CD is higher among individuals who have first-degree relatives with CD. HLA-DQ2 homozygosity is associated with a significantly increased risk of CDA and CD amongst first-degree relatives. Data from the PreventCD study and CELIPREV study suggests that very early development of CDA and CD (below 3-5 years of age) affects preferentially children carrying the very high risk CD alleles (HLA-DQ2.5 homozygous), which are found in only 1-2% of the general population but in 10-15% of children with first-degree relatives having CD. These infants may potentially benefit from later gluten introduction.
It could be argued that delaying gluten introduction towards the end of the first year may be considered in all infants from CD families, in order to reduce the risk of early presentation of the disease and the potential adverse effects on growth and development at a young age, despite the fact that delayed introduction may only benefit the 10-15% with high-risk alleles. However, an alternative approach could be to screen (e.g. HLA typing) all children born into families with a first-degree relative with CD to identify infants with high-risk alleles followed by serological testing post gluten-introduction to detect CD before nutritional deficiencies develop. It was recognised that recommendations on screening were beyond the scope of this position paper.
Summary
A number of important questions remain. Further research, specifically multicentre and multinational RCTs, is required to help answer these including the optimal type and amount of gluten to be included at introduction to the diet, as well as, whether delaying gluten introduction for longer than a year would reduce long-term prevalence of CD (the pros and cons of this approach need to be considered). Finally, as primary prevention is not feasible, mass screening remains an open question; specific recommendations on screening strategies for CD in risk groups such as in children with family members affected with CD are required.
Click to read abstract
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