Timing Of Gluten Introduction Research Articles

Elucidating the non-genetic risk factors for celiac disease: an umbrella review of meta-analyses.

The breadth and validity of the associations of nongenetic risk factors with celiac disease (CeD) are elusive in the literature. We aimed to evaluate which of these associations have strong epidemiological credibility and assessed presence and extent of potential literature biases. We systematically searched PubMed until April 2024 for systematic reviews and meta-analyses of studies examining associations between putative risk factors and CeD. Each association was categorized in five evidence grades (convincing, highly suggestive, suggestive, weak, and not statistically significant) based on broadly used criteria for evaluating quality of evidence in observational studies. Five eligible publications were included, describing 15 meta-analytic associations on seven nongenetic risk factors, three of which were nominally significant ( P < 0.05). None of the associations received a strοng or highly suggestive evidence. One meta-analytic association received suggestive evidence, namely any infections during childhood and adulthood for a higher risk of CeD (OR, 1.37; 95% CI, 1.2-1.56; P =3.77 × 10 -6 ). Two meta-analyses reported weak evidence, pertaining to current smoking for a lower risk of CeD (OR, 0.52; 95% CI, 0.32-0.84; P =7.84 × 10 -3 ) and use of antibiotics for a higher risk (OR, 1.2; 95% CI, 1.04-1.38; P 14.8 × 10 -3 ). The rest of the meta-analyses did not report statistically significant results, and pertained to breastfeeding, time of gluten introduction, rotavirus vaccination, and cesarean section. No association of nongenetic risk factors for CeD received high levels of evidence. The evidence was suggestive for the association of any infections during childhood and adulthood with higher risk of CeD. More and prospective future research is warranted.

A case-control epidemiological survey on potential risk factors for celiac disease.

Celiac disease (CD) is a chronic autoimmune disorder caused by a complex interplay between genetic and environmental factors. The main goal of our case-control study was to analyse the association of environmental factors with the odds of CD development in a sample of the Slovak population. Data were collected from 1,226 respondents (534 CD patients and 692 controls) by a questionnaire. The impact of analysed parameters on the chance of disease development was assessed by multiple regression analysis and expressed as odds ratios (OR). Values of p < 0.05 were considered statistically significant. In the patient group, celiac disease was significantly more prevalent in women than in men (OR = 1.52, p = 0.010). Respondents with a positive family history of CD showed 2.9-fold higher odds of CD compared to others (p < 0.001), and respondents with coexisting autoimmune diseases had 2.6-fold higher odds of CD (p < 0.001). Subjects who had taken antibiotics at least three times a year during childhood had 1.95-fold higher odds of developing CD compared to those who took them less frequently or not at all (p = 0.022). Conversely, individuals who were breastfed in infancy had lower odds of CD compared to non-breastfed respondents (OR = 0.53, p < 0.001). The mode of delivery (vaginal vs. caesarean section), overcoming severe infections, and the timing of gluten introduction in childhood did not show a statistically significant effect on the odds of developing CD. Based on our data, being female, having a positive family history of CD, suffering from another autoimmune disease, and frequent use of antibiotics are factors associated with an increased chance of developing CD. On the other hand, breastfeeding in infancy seems to have a protective effect. Our findings highlight the importance of further research in understanding the complexities of this autoimmune condition and providing a foundation for prevention strategies.

A Population-Based Cross-Sectional Study of Paediatric Coeliac Disease in Catalonia Showed a Downward Trend in Prevalence Compared to the Previous Decade.

(1) Background: Previous studies showed an increased prevalence and incidence of coeliac disease (CD) over time. The objective is to ascertain whether the CD prevalence in Catalonia (a region of Southern Europe) among children aged 1-5 is as high as previously found in 2004-2009; (2) Methods: From 2013 to 2019, 3659 subjects aged 1-5 years were recruited following the previously used methodology. Factors with a potential impact on CD prevalence were investigated; (3) Results: In 2013-2019, 43/3659 subjects had positive serology, giving a standardised seroprevalence of 12.55/1000 (95% CI: 8.92; 17.40), compared to 23.62 (13.21; 39.40) in 2004-2007. The biopsy-proven crude prevalence was 7.92/1000 (95% CI: 5.50; 11.30), and the crude prevalence based on ESPGHAN criteria was 8.74/1000 (95% CI: 6.20-12.30). In contrast to 2004-2009, we did not find differences in the seroprevalence rates between 1 and 2 years vs. 3 and 4 years of age (age percentage of change -7.0 (-29.5; 22.8) vs. -45.3 (-67.5; -8.0)). Rotavirus vaccination was the most remarkable potential protective factor (48% vs. 9% in 2004-2009; p < 0.0001), but not the time of gluten introduction. (4) Conclusion: The present study did not confirm a worldwide CD prevalence increase and emphasizes the need to perform prevalence studies over time using the same methodology in the same geographical areas.

Review article: Becoming and being coeliac-special considerations for childhood, adolescence and beyond.

Classically considered a disease of early childhood characterised by malabsorption and failure to thrive, coeliac disease is now recognised to arise in genetically susceptible individuals at any age. Although permissive HLA genotypes are the strongest predictor of coeliac disease, they are not sufficient. Several prospective cohort studies enrolling genetically at-risk infants have investigated the role of potential triggers of coeliac disease autoimmunity, such as timing of gluten introduction, viral infections and dietary patterns. Much less is known about triggers of coeliac disease in adulthood. Better understanding of factors leading to coeliac disease may be helpful in the management of those with potential coeliac disease (elevated serum celiac antibodies without villous atrophy in the small intestine), many of whom initiate a gluten-free diet without demonstration of villous atrophy. There are a range of clinical presentations of celiac disease in childhood and patterns of coeliac serology, including fluctuation and spontaneous reversion on a gluten-containing diet, vary. There is a current debate over best strategies to manage adults and children with potential coeliac disease to avoid over-treatment and under-treatment. Childhood and adolescence carry unique issues pertaining to the diagnosis and management of coeliac disease, and include nutrition and growth, rescreening, repeat biopsy, dietary adherence concerns and transition to adult care. In conclusion, while coeliac disease has similar pathogenesis and general clinical manifestations in paediatric and adult populations, diagnostic and management approaches need to adapt to the developmental stages.

A10 EARLY LIFE SENSITIZATION TO GLUTEN INDUCES SUSTAINED IMMUNOPATHOLOGY IN DR3-DQ2 MICE

Abstract Background Celiac disease (CeD) is an autoimmune T-cell mediated enteropathy, triggered by gluten, a group of proteins found in wheat, barley, and rye. The defined role of gluten as a dietary trigger, necessary genes (HLA-DQ2 and/or DQ8), and tissue transglutaminase (TG2) as the autoantigen together, are unique features of CeD. Although CeD onset can occur at any age, first dietary introduction of gluten during infancy is a critical window of exposure, especially in infants homozygous for the HLA DQ2.5 allele. While adult sensitization studies have been recently performed in DR3-DQ2 mice, the consequences of early life gluten sensitization timing remain unexplored. Aims Our aim was to characterize gluten-immunopathology and CeD-specific serology in specific pathogen free (SPF) DR3-DQ2 transgenic mice sensitized to gluten, 1 week before weaning. Methods Seven-week-old SPF DR3-DQ2 transgenic mice, kept on a gluten-free diet (GFD), were paired for breeding. At post-natal day 3, pups were standardized to 4 per litter (n=2 male, n=2 female) to ensure equal nutrition across litters. At 14 days of age, pups were sensitized with pepsin-trypsin digested gliadin and cholera toxin (CT) three times in one week (n=15). At 21 days of age, pups were weaned and placed either on a gluten-containing diet (n=7), (equivalent of 20g/d of gluten in a human diet -high dose-) or an isocaloric GFD (n=8) until 10 weeks of age. Non-sensitized controls (n=7) received only CT and were kept on the GFD. At sacrifice, serum was collected for anti-TG2 and anti-gliadin antibodies (AGA). Jejunal tissue was collected for histological analysis using villus-to-crypt (V/C) ratios and CD3+ intraepithelial lymphocytes (IEL) counts. Results Gluten-sensitized mice placed on a gluten-containing diet post-weaning had lower V/C ratios and higher CD3+ IEL counts compared with controls (p&amp;lt;0.01). Pre-weaning sensitized mice that were kept on a GFD post-weaning had sustained decreases in V/C ratios and higher CD3+ IEL counts (p&amp;lt;0.01). Out of 15 sensitized mice, 7 developed positive anti-gliadin IgA (p=0.02) and 4 had positive anti-TG2 IgA antibodies (p=0.01) in intestinal contents, irrespective of gluten in the diet. None of the controls had detectable AGA or anti-TG2 antibodies. Conclusions Pre-weaning gluten sensitization of DR3-DQ2 mice induced prolonged gluten immunopathology that did not reverse after 5 weeks on a GFD. Our results indicate that young DR3-DQ2 mice are susceptible to gluten sensitization, with sustained immunopathology, suggesting a critical window of vulnerability in familial carriers of DQ2.5. This novel model will be useful to investigate environmental cofactors at the first time of gluten introduction to the diet. Funding Agencies CIHR

To Wheat or not to Wheat: Timing of Gluten Introduction

Hall, Ashley U. MD, FACOG; Meisenheimer, Erica S. MD, MBA, FAAFP; Thiel, Derrick J. MD; Marshall, Bob MD MPH, MISM, FAAFP Author Information

Influence of breastfeeding and timing of gluten introduction on the onset of celiac disease in infants

Introduction/Objective. The classic type of celiac disease (CD) is most common in children under two years of age. The aim of this study was to investigate whether breastfeeding, particularly breastfeeding during gluten introduction, and timing of gluten introduction, influence the onset of CD at this age. Methods. We retrospectively analyzed medical records of 93 children, 40 in the first and 53 in the second year, with a classic CD diagnosed at the University Children?s Hospital, Belgrade between 2000 and 2010. The diagnosis of CD was based on the criteria of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) from 1989. Results. Duration of breastfeeding reduced the onset of the CD in the first year p = 0.039 (OR = 1.43 95% CI 1.019?1.899). Also, breastfeeding at the time of gluten introduction significantly delayed the age at diagnosis (F = 1.671, t = 2.39, p = 0.029). The timing of gluten introduction did not affect the age of occurrence of CD in these group of children. Conclusion. Longer breastfeeding, and breastfeeding at the time of gluten introduction, postponed the onset of classic CD in patients up to two years. The association between the occurrence of CD and the time of introduction of gluten in this age group of patients has not been established.

Celiac Disease Prevention

Celiac disease (CD) is a common autoimmune disorder induced by ingestion of gluten in genetically susceptible individuals. Despite the prerequisite for a genetic predisposition, only a minority of the 40% of the Caucasian population that has this genetic predisposition develops the disease. Thus, environmental and/or lifestyle factors play a causal role in the development of CD. The incidence of CD has increased over the last half-century, resulting in rising interest in identifying risk factors for CD to enable primary prevention. Early infant feeding practices have been suggested as one of the factors influencing the risk of CD in genetically susceptible individuals. However, recent large prospective studies have shown that neither the timing of gluten introduction nor the duration or maintenance of breastfeeding influence the risk of CD. Also, other environmental influences have been investigated as potential risk factors, but have not led to primary prevention strategies. Secondary prevention is possible through early diagnosis and treatment. Since CD is significantly underdiagnosed and a large proportion of CD patients are asymptomatic at the time of diagnosis, secondary prevention will not identify all CD patients, as long as mass screening has not been introduced. As following a gluten-free diet is a major challenge, tertiary prevention strategies are discussed as well.

Does infant feeding modulate the manifestation of celiac disease and type 1 diabetes?

The review aims to critically discuss the role of infant feeding in the development of celiac disease and type 1 diabetes (T1D). Prospective observational and randomized interventional studies show that breastfeeding (BF) or BF during gluten introduction does not reduce the risk of developing CD, but high gluten consumption before age 2 years increased the risk in Swedish children.Despite evidence from retrospective studies, prospective trials failed to find a protective effect of breastfeeding against the risk of T1D development. Nevertheless, breastfeeding at the time of cereal introduction decreases this risk. There is some evidence demonstrating that early exposure to sugar-sweetened beverages increases the risk of T1D in childhood, whereas the timing of gluten introduction, except if introduced very early, does not affect it. Breastfeeding and/or timing of gluten introduction does not influence celiac disease risk. Breastfeeding at the time of cereal introduction might be protective against T1D. The introduction of certain solid foods at an early age may be associated with the risk of T1D.

Systematic Review: Early Infant Feeding and the Risk of Type 1 Diabetes.

In addition to genetic background, a number of environmental factors have been claimed to influence the development of type 1 diabetes (T1D), including infant diet. The aim of the study was to systematically update evidence on the possible relation between early feeding practices and the risk of T1D. The Cochrane Library, MEDLINE, EMBASE, Web of Science, and CINAHL were searched for studies of any design up to July 2015. MEDLINE and EMBASE were additionally searched in March 2016. The primary outcome measures were the development of T1D or T1D-associated autoimmunity (T1DA). Nine publications were identified. Breastfeeding at the time of gluten introduction, as compared to gluten introduction after weaning, did not reduce the risk of developing T1DA or T1D. In children at high risk of developing T1D, except for gluten introduction at 3 months or younger age compared with gluten introduction at older than 3 months, which increased the risk of T1DA, the age of gluten introduction in infants had no effect on the risk of developing T1DA. Current evidence, mainly from observational studies, does not support the claim that early infant feeding practices, such as breastfeeding at gluten introduction or the age of the infant at the time of gluten introduction, may decrease the risk of developing T1D. More robust data are needed from randomized controlled trials.

Timing of Allergenic Food Introduction to the Infant Diet and Risk of Allergic or Autoimmune Disease: A Systematic Review and Meta-analysis.

Timing of introduction of allergenic foods to the infant diet may influence the risk of allergic or autoimmune disease, but the evidence for this has not been comprehensively synthesized. To systematically review and meta-analyze evidence that timing of allergenic food introduction during infancy influences risk of allergic or autoimmune disease. MEDLINE, EMBASE, Web of Science, CENTRAL, and LILACS databases were searched between January 1946 and March 2016. Intervention trials and observational studies that evaluated timing of allergenic food introduction during the first year of life and reported allergic or autoimmune disease or allergic sensitization were included. Data were extracted in duplicate and synthesized for meta-analysis using generic inverse variance or Mantel-Haenszel methods with a random-effects model. GRADE was used to assess the certainty of evidence. Wheeze, eczema, allergic rhinitis, food allergy, allergic sensitization, type 1 diabetes mellitus, celiac disease, inflammatory bowel disease, autoimmune thyroid disease, and juvenile rheumatoid arthritis. Of 16 289 original titles screened, data were extracted from 204 titles reporting 146 studies. There was moderate-certainty evidence from 5 trials (1915 participants) that early egg introduction at 4 to 6 months was associated with reduced egg allergy (risk ratio [RR], 0.56; 95% CI, 0.36-0.87; I2 = 36%; P = .009). Absolute risk reduction for a population with 5.4% incidence of egg allergy was 24 cases (95% CI, 7-35 cases) per 1000 population. There was moderate-certainty evidence from 2 trials (1550 participants) that early peanut introduction at 4 to 11 months was associated with reduced peanut allergy (RR, 0.29; 95% CI, 0.11-0.74; I2 = 66%; P = .009). Absolute risk reduction for a population with 2.5% incidence of peanut allergy was 18 cases (95% CI, 6-22 cases) per 1000 population. Certainty of evidence was downgraded because of imprecision of effect estimates and indirectness of the populations and interventions studied. Timing of egg or peanut introduction was not associated with risk of allergy to other foods. There was low- to very low-certainty evidence that early fish introduction was associated with reduced allergic sensitization and rhinitis. There was high-certainty evidence that timing of gluten introduction was not associated with celiac disease risk, and timing of allergenic food introduction was not associated with other outcomes. In this systematic review, early egg or peanut introduction to the infant diet was associated with lower risk of developing egg or peanut allergy. These findings must be considered in the context of limitations in the primary studies.

Early Infant Feeding Practices May Influence the Onset of Symptomatic Celiac Disease

Background: Infant feeding practices may play an important role in subsequent development of celiac disease in children. Aim: To study the influence of the breastfeeding and breastfeeding status during gluten introduction influence the age at diagnosis of celiac disease. In addition, to study whether timing of gluten introduction influence the age at diagnosis of celiac disease. Material and methods: It was a hospital based observational prospective study carried out at Department of Pediatrics, SMS Medical College Jaipur. Total 198 patients with symptomatic celiac disease diagnosed as per modified ESPGHAN (2012) criteria aged between 6 month and 6 years were included in the study after obtaining informed written consent. Detail history was taken with special emphasis on duration and pattern of breastfeeding and age of gluten introduction. The data was analyzed using standard statistical methods. Results: Mean (SD) age of onset & diagnosis of celiac disease in children who had been breastfed was 2.81(1.42) years & 3.68 (1.55) years respectively whereas it was 1.84 (1.36) years & 2.7 (1.65) years respectively in children who were not breastfed (p < .05). Those who had more prolonged breast feeding and had continued it beyond the month of gluten introduction had significantly delayed onset of disease. 40 % of those who had started gluten before 6 months of age had age at onset of disease < 1year as compared to 12.41 % of those who had started gluten after 6 months (p< .001). Conclusion: Prolonged breast feeding and continuing breast feeding during gluten introduction and beyond it has protective value. Also delayed introduction of gluten in infant diet delays symptomatic celiac disease.

Gluten Intake and Risk of Developing Celiac Disease

Research Article| August 01 2016 Gluten Intake and Risk of Developing Celiac Disease AAP Grand Rounds (2016) 36 (2): 13. https://doi.org/10.1542/gr.36-2-13 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation Gluten Intake and Risk of Developing Celiac Disease. AAP Grand Rounds August 2016; 36 (2): 13. https://doi.org/10.1542/gr.36-2-13 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search toolbar search search input Search input auto suggest filter your search All PublicationsAll JournalsAAP Grand RoundsPediatricsHospital PediatricsPediatrics In ReviewNeoReviewsAAP NewsAll AAP Sites Search Advanced Search Topics: celiac disease, gluten Source: Aronsson AC, Lee HS, Koletzko S, et alTEDDY Study Group. Effects of gluten intake on risk of celiac disease: A case-control study on a Swedish birth cohort. Clin Gastroenterol Hepatol. 2016; 14(3): 403– 409.e3; doi: https://doi.org/10.1016/j.cgh.2015.09.030Google Scholar Investigators from multiple institutions enrolled child participants from the Swedish site of The Environmental Determinants of Diabetes in the Young (TEDDY) study to assess the association between gluten intake before 2 years of age and the risk of developing celiac disease (CD). As part of the TEDDY study, participants were screened for CD annually beginning at age 2 years using serum tissue transglutaminase (TTGA). Participants with 2 consecutive positive TTGA samples were referred to their health care provider for evaluation of CD with an intestinal biopsy; a biopsy showing a Marsh score of ≥2 was considered proof of CD.1 For the current study, investigators categorized Swedish TEDDY participants as cases if they had biopsy-confirmed CD. Three controls who were TTGA-negative were matched to each case on gender, year of birth, and presence of HLA genotypes considered to confer increased risk for CD. The primary exposure was the amount and timing of gluten intake. This was measured using a 24-hour parent recall of the child’s food consumption at age 3–4 months and 3-day standardized food intake records completed by parents before study visits at 6, 9, 12, 18, and 24 months of age. At each visit, food records were reviewed by a study nurse. Gluten-containing foods were considered to be products and composite dishes containing wheat, rye, or barley. The mean intake of gluten was calculated as grams per day. The investigators compared timing and amount of gluten intake among cases and controls and used logistic regression to compare characteristics in cases and controls. Data were analyzed on 146 cases and 436 matched controls. Timing of introduction to gluten-containing foods was the same (a median age of 22 weeks) for cases and controls. However, the amount of gluten intake among cases was significantly more than in controls at the 12- and 24-month time points. Overall, a 1 g/day increase of gluten was associated with a 28% increase in risk of CD (P = .0002). This association did not differ between case-control pairs when HLA genotype was considered. The authors conclude that the amount of gluten consumed prior to 2 years of age increased the risk of CD and was independent of HLA genotype. Drs LeLeiko and Silverstein have disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device The results of this study suggest that the amount of gluten ingestion in the first 2 years of life affects the risk of CD. The study findings also help explain why some, but not all, children at genetic risk develop CD. Furthermore, the results suggest that timing of gluten introduction, a variable once thought to impact... You do not currently have access to this content.

Issue Highlights

Issue Highlights

Infant feeding and risk of developing celiac disease: a systematic review

ObjectiveTo review the evidence for the association of breast feeding, breastfeeding duration or the timing of gluten introduction and the later development of celiac disease (CD).DesignSystematic review.MethodsWe searched MEDLINE, via...

The Role of Environmental Factors in the Development of Celiac Disease: What Is New?

Celiac disease (CD) is a systemic immune-mediated disorder caused by the ingestion of gluten-containing grains in genetically susceptible persons. It is one of the most common lifelong disorders, affecting approximately 1% of the general population. The prevalence of CD has increased in developed countries over recent decades, pointing to the role of additional environmental triggers other than gluten. It has been hypothesized that intestinal infections, the amount and quality of gluten, the intestinal microbiota, and early nutrition are all possible triggers of the switch from tolerance to an immune response to gluten. Two recent randomized controlled trials have been performed to clarify the relationship between the age at which gluten is introduced to a child’s diet and the risk of CD, showing that timing of gluten introduction does not modify the risk of CD. Both trials also showed that breastfeeding compared with no breastfeeding or breastfeeding duration or breastfeeding during gluten introduction have no effect on the risk of CD. The two trials, although not designed to address this issue, have shown that intestinal infections seem not to influence the risk of CD. Further studies are still needed to explore the missing environmental factors of CD for future prevention.

Risk factors for celiac disease.

Celiac Disease (CD) is an immune-mediated systemic disorder elicited by gluten and related prolamines in genetically susceptible individuals and it is the result of the interaction between genetic and environmental factors. Among genetic risk factors, the strongest association is with the HLA class II DQ region; nevertheless at least 39 non-HLA loci are associated with CD. Gluten is the main environmental trigger of the disease. In addition, infant feeding and weaning practices as well as timing of gluten introduction in the diet have been suggested to contribute to CD risk. Furthermore a role for infectious agents and microbiota composition in disease development has also been proposed.Aim of this short review is to discuss the current knowledge on both genetic and environmental risk factors for the development of CD; moreover we will provide a brief overview of the possible strategies that could be envisaged to prevent this condition, at least in the population at-risk.

Systematic review with meta-analysis: early infant feeding and coeliac disease--update 2015.

New evidence emerged on early feeding practices and the risk of coeliac disease. To systematically update evidence on these practices to find out whether there is a need to revise current recommendations. MEDLINE, EMBASE and the Cochrane Library were searched from July 2012 (end of last search) to February 2015 for studies of any design that assessed the effect of gluten consumption and breastfeeding on the development of coeliac disease and/or coeliac disease-related autoimmunity. We identified 21 publications, including two, new, large, randomised controlled trials performed in high-risk infants. Exclusive or any breastfeeding, as well as breastfeeding at the time of gluten introduction, did not reduce the risk of developing coeliac disease during childhood. For infants at high risk of developing coeliac disease, gluten introduction at 4months of age in very small amounts, or at 6 or 12months of age, resulted in similar rates of coeliac disease diagnosis in early childhood. Later gluten introduction was associated with later development of coeliac specific autoimmunity and coeliac disease during childhood, but not total risk reduction. Observational studies indicate that consumption of a higher amount of gluten at weaning may increase the risk for coeliac disease development. Infant feeding practices (breastfeeding, time of gluten introduction) have no effect on the risk of developing coeliac disease during childhood (at least at specific timeframes evaluated in the included studies), necessitating an update of current European recommendations.

O-172 Infant Feeding And Anti-tissue Transglutaminase Antibody Levels In Children With Subclinical Celiac Disease: The Generation R Study

Objective To examine whether the timing of gluten introduction and breastfeeding duration are associated with subclinical celiac disease in children at the age of 6 years. Methods This study was embedded in the Generation R study, a population-based prospective cohort study. Participants included 1679 Dutch children positive for HLA-DQ2/DQ8. Data on the timing of gluten introduction ( 7 U/ml) levels. Positive anti-tTG levels were further categorised based on the ≥10 times upper limit of normal (ULN) levels of the test kit (>7–70 U/ml and ≥70 U/ml). Multivariable logistic regression analyses were performed. Results Positive anti-tTG levels were found in 43 children of which 26 children had levels above the 10 times ULN (≥70 IU/ml). The introduction of gluten from the age of 6 months onwards and breastfeeding for 6 months or longer were not significantly associated with positive anti-tTGlevels. In addition, the timing of gluten introduction and duration of breastfeeding were not significantly associated with positive anti-tTG levelsbelow and above the 10 times ULN. Conclusions Delayed introduction of gluten beyond the age of 6 months does not increase the risk of subclinical CD. Also, breastfeeding for 6 months or longer does not decrease the risk of subclinical CD in children at 6 years of age.

Infant feeding and anti-tissue transglutaminase antibody concentrations in the Generation R Study

Celiac disease (CD) has emerged as a common, but largely undiagnosed health problem. Numerous studies examined the influence of infant nutrition on the development of diagnosed CD. However, results are still inconsistent. In addition, the effect of infant feeding practices on the development of potential forms of CD might be different. The objective was to examine whether the timing of gluten introduction and breastfeeding duration are associated with CD autoimmunity (CDA) in children at the age of 6 y. This study was embedded in the Generation R Study, a population-based prospective cohort study. Participants included 1679 Dutch children who were positive for human leukocyte antigen (HLA) DQ2/DQ8. Data on the timing of gluten introduction (<6 mo compared with ≥6 mo) and duration of breastfeeding (<6 mo compared with ≥6 mo) were obtained by questionnaire. Serum samples were analyzed for anti-tissue transglutaminase (anti-tTG) concentrations at age 6 y. Anti-tTG concentrations were categorized into negative (<7 U/mL) and positive (≥7 U/mL) values. Positive anti-tTG concentrations were further categorized based on ≥10 times the upper limit of normal (ULN) values of the test kit (≥7-70 and ≥70 U/mL). Multivariable logistic regression analyses were performed. Positive anti-tTG concentrations were found in 43 children, 26 of whom had concentrations ≥10 times the ULN (≥70 IU/mL). The introduction of gluten from the age of 6 mo onward and breastfeeding for ≥6 mo were not significantly associated with positive anti-tTG concentrations. In addition, the timing of gluten introduction and duration of breastfeeding were not significantly associated with positive anti-tTG concentrations below or above 10 times the ULN. Delayed introduction of gluten beyond the age of 6 mo does not increase the risk of CDA. In addition, breastfeeding for ≥6 mo does not decrease the risk of CDA in children at 6 y of age.