Introduction of Gluten, HLA Status, and the Risk of Celiac Disease in Children

Lionetti, Elena; Castellaneta, Stefania; Francavilla, Ruggiero; Pulvirenti, Alfredo; Tonutti, Elio; Amarri, Sergio; Barbato, M.; Barbera, Cristiana; Barera, Graziano; Bellantoni, Antonella; Castellano, E.; Guariso, Graziella; Limongelli, M.G.; Pellegrino, Salvatore; Polloni, Carlo; Ughi, C; Decorti, Giuliana; Fasano, Alessio; Catassi, Carlo

doi:10.1056/nejmoa1400697

Cited by 425 publications

(416 citation statements)

References 37 publications

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“…Some epidemiological studies have proposed that milk feeding practices and intestinal infections could play a role as predisposing factors, but to date, a causal relationship remains unconfirmed. 3 , 35 , 36 In the present study, we have assessed the prevalence of six potential pathogenic bacteria and two viruses causing gastrointestinal infections in healthy infants at familial risk of developing CD. Overall, we found that some pathogenic bacteria are specifically associated with the formula feeding pattern ( C .…”

Section: Discussionmentioning

confidence: 99%

Increased prevalence of pathogenic bacteria in the gut microbiota of infants at risk of developing celiac disease: The PROFICEL study

et al. 2018

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Celiac disease (CD) is an immune-mediated enteropathy involving genetic and environmental factors, whose interaction influences disease risk. The intestinal microbiota, including viruses and bacteria, could play a role in the pathological process leading to gluten intolerance. In this study, we investigated the prevalence of pathogens in the intestinal microbiota of infants at familial risk of developing CD. We included 127 full-term newborns with at least one first-degree relative with CD. Infants were classified according to milk-feeding practice (breastfeeding or formula feeding) and HLA-DQ genotype (low, intermediate or high genetic risk). The prevalence of pathogenic bacteria and viruses was assessed in the faeces of the infants at 7 days, 1 month and 4 months of age. The prevalence of Clostridium perfringens was higher in formula-fed infants than in breast-fed over the study period, and that of C. difficile at 4 months. Among breastfed infants, a higher prevalence of enterotoxigenic E. coli (ETEC) was found in infants with the highest genetic risk compared either to those with a low or intermediate risk. Among formula-fed infants, a higher prevalence of ETEC was also found in infants with a high genetic risk compared to those of intermediate risk. Our results show that specific factors, such as formula feeding and the HLA-DQ2 genotype, previously linked to a higher risk of developing CD, influence the presence of pathogenic bacteria differently in the intestinal microbiota in early life. Further studies are warranted to establish whether these associations are related to CD onset later in life.

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Section: Discussionmentioning

confidence: 99%

Increased prevalence of pathogenic bacteria in the gut microbiota of infants at risk of developing celiac disease: The PROFICEL study

et al. 2018

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“…Although wheat allergy and celiac disease are two different types of immune-mediated hypersensitivity reactions, a meta-analysis has shown a 25% increased risk of developing celiac disease if gluten is introduced after 6 months of age, as compared with introduction between 4 and 6 months of age [38]. On the other hand, the timing of introduction of gluten was not found to affect the development of celiac disease in two large randomized controlled trials of high-risk infants [39,40]. …”

Section: Discussionmentioning

confidence: 99%

Late introduction of fish and eggs is associated with increased risk of allergy development – results from the FARMFLORA birth cohort

Jönsson

Barman

Brekke

et al. 2017

Food & Nutrition Research

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The prevalence of allergy is markedly low in children growing up on farms. An increasing number of studies indicate that the timing of food introduction may affect allergy development. We aimed to investigate if protection against allergy in farm environments may be mediated through differences in food-introduction practices between farm and non-farm families, using an explorative approach. Twenty-eight farm and 37 non-farm children were included in the FARMFLORA birth cohort. Practices of breastfeeding and introduction of formulas and complementary foods were collected by questionnaires at 6, 12, and 18 months of age. Allergy was diagnosed by pediatricians at 3 years of age. The only difference in food-introduction practices observed between farm and non-farm children was an earlier introduction of nuts in farmers (median month: 11 [IQR: 8–6] in farmers, 15 [12–19] in non-farmers). One farm child (4%) and 10 non-farm children (27%) were allergic at 3 years of age. Lower risk of allergy development was associated with early exclusive breastfeeding (continuous variable; OR = 0.59, 95% CI: 0.39–0.89), but also having received eggs (OR = 0.08, 95% CI: 0.13–0.54) and fish (logistic regression not applicable, P = 0.01 in likelihood ratio testing [χ2]) at 10 months of age or earlier compared to later. Our results were not affected by reverse causation, as judged by a questionnaire sent to the families in retrospect. Timing of introduction of complementary foods is unlikely to contribute to the lower risk of allergy among farm children. Although early exclusive breastfeeding was associated with a lower rate of allergy development, postponed introduction of complementary foods might increase the risk of developing allergy. Owing to the limited sample size, our results are only indicative, but support prior findings.

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“…These findings suggest that primary prevention of CD through nutritional interventions is not possible at the present time. 17,18 Meanwhile, new observational evidence shows no difference in CD risk when gluten is introduced while the infant is still breast-feeding, compared to after weaning. Because of its many other health benefits, breastfeeding is recommended for all infants, regardless of celiac disease risk.…”

Section: Weaning and Celiac Diseasementioning

confidence: 99%

Weaning and complementary feeding in preterm infants: management, timing and health outcome

Barachetti¹,

Villa²,

Barbarini³

2017

Pediatr Med Chir

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The introduction of solid food is necessary for any infant in order to provide adequate nutrition because when they grow up milk is insufficient for their nutritional needs. Infants born preterm have increased nutritional requirements. The high nutrient demands as well as the organ immaturity of preterm infants combine to render it difficult to achieve dietary intakes that will allow preterm infants to match their in utero growth rates. Current guidelines for the introduction of solid food to term infants cannot be directly translated to preterm infants. For preterm infants such guidelines are lacking. Based on the limited available evidence, it could be concluded that a corrected age of 3 months (13 weeks) may be an appropriate age to start introducing solid food for most preterm infants. About celiac disease (CD), gluten may be introduced into the infant’s diet anytime between 4 and 12 completed months of age. In children at high risk for CD, earlier introduction of gluten (4 vs 6 months or 6 vs 12 months) is associated with earlier development of CD autoimmunity (defined as positive serology) and CD, but the cumulative incidence of each in later childhood is similar. Relatively to weaning and allergies, the European Society of Pediatric Allergy and Clinical Immunology and the European Society for Paediatric Gastroenterology Hepatology and Nutrition have produced joint guidelines. They recommend exclusive breastfeeding for 4–6 months or use of hypoallergenic formulas if exclusive breastfeeding is not possible. In addition, The American Academy of Pediatrics recommendations now state that there is no evidence to recommend maternal dietary restrictions during pregnancy or breastfeeding. However, there is no evidence that delaying introduction of solids including allergenic foods after 4–6 months is protective.

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Introduction of Gluten, HLA Status, and the Risk of Celiac Disease in Children

Cited by 425 publications

References 37 publications

Increased prevalence of pathogenic bacteria in the gut microbiota of infants at risk of developing celiac disease: The PROFICEL study

Increased prevalence of pathogenic bacteria in the gut microbiota of infants at risk of developing celiac disease: The PROFICEL study

Late introduction of fish and eggs is associated with increased risk of allergy development – results from the FARMFLORA birth cohort

Weaning and complementary feeding in preterm infants: management, timing and health outcome

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