Timing Of Gluten Introduction Research Articles

Breast‐feeding Duration and Gluten Introduction Among Mothers With Celiac Disease

Both breast-feeding duration and age at gluten introduction have been implicated in the pathogenesis of celiac disease (CD). We hypothesized that parental CD affects the feeding pattern of the offspring, mediated by parental health awareness increasing adherence to infant feeding guidelines. Prospectively collected infant feeding data were obtained through the All Babies in Southeast Sweden study. Information regarding infant feeding was available in 9414 children. Twenty-two mothers had a history of biopsy-verified CD before delivery of a child in the study, and 9392 mothers had no diagnosis of CD before birth and thus constituted the unexposed or control population. Cox regression was used to compare the risk of early weaning and gluten introduction according to parental CD status, and logistic regression to assess whether mothers with CD were more likely to breast-feed their children at gluten introduction. Some 63% of children were breast-fed for at least 9 months. We found no association between maternal CD and early weaning (adjusted hazard ratio [HR] 1.0, 95% confidence interval [CI] 0.6-1.7), or between paternal CD and early weaning (HR 0.5, 95% CI 0.1-1.9). Sixty percent of children were introduced to gluten in months 5 and 6. Maternal CD was not associated with age at gluten introduction (adjusted HR 0.8, 95% CI 0.6-1.3). There was no statistically significant association between maternal CD and breast-feeding at the time of gluten introduction (odds ratio 1.4, 95% CI 0.4-4.7). Feeding patterns do not seem to vary between offspring and mothers with CD and those without.

Infectious Disease at Gluten Introduction and Risk of Childhood Diabetes Mellitus

To investigate the risk of future diabetes mellitus type 1 (T1D) in children who suffered from infection at time of gluten introduction. Population-based prospective study. Parents filled out a diary at home. We hereby obtained data on date of gluten introduction, breastfeeding duration, and infections in 9414 children born in the southeast of Sweden from October 1, 1997, through October 1, 1999 (the All Babies in Southeast Sweden cohort). The Cox proportional hazards model was used to investigate the risk of future T1D until February 1, 2012, among children with infection at time of gluten introduction. Forty-six children (0.5%) developed T1D and were compared with 9368 reference children from the general population. Some 10 of 46 children with later T1D had an infection at time of gluten introduction (22%) compared with 2520 reference children (27%, P=.43). Later T1D was not associated with age at end of breastfeeding, age at any infection, or age at gluten introduction. Breastfeeding at time of gluten introduction was not protective against future T1D (hazard ratio 1.2; 95% CI, 0.5-2.7). In our final model, when we adjusted for age at gluten introduction, age at infection, and breastfeeding duration, infection at time of gluten introduction did not influence the risk of future T1D (hazard ratio 0.8; 95% CI, 0.3-1.6). Infection at time of gluten introduction is not a major risk factor for future T1D in nonselected children.

Early Feeding and Risk of Celiac Disease in a Prospective Birth Cohort

Timing of gluten introduction has been associated with the risk of celiac disease (CD) in children, but the optimal time window is unknown. We aimed to study the effect of age of gluten introduction on the risk of CD, adjusting for continued breastfeeding. In The Norwegian Mother and Child Cohort Study, a prospective birth cohort including 107,000 children, CD was identified by questionnaires and by linkage to the Norwegian Patient Register. Gluten introduction was reported monthly from 0 to 6 months of age, and breastfeeding from 0 to 18 months. After exclusion of cases with insufficient information, 324 children with CD in a cohort of 82,167 were used in the analyses. Gluten was introduced before or at 4 months in 8.0%, 5 to 6 months in 45.3%, and after 6 months in 46.6%, whereas continued breastfeeding was stable at ≈ 78% at 6 months age. CD was diagnosed in 3.68/1000 of the infants with gluten introduction at 5 to 6 months compared with 4.15/1000 with late and 4.24/1000 with early gluten introduction. After adjustment for the child's age and gender, breastfeeding, and maternal CD, delayed gluten introduction was associated with an increased risk of CD (adjusted odds ratio, 1.27 [95% confidence interval, 1.01-1.65], P = .045). Breastfeeding >12 months was also associated with increased risk (adjusted odds ratio, 1.49 [95% confidence interval, 1.01-2.21], P = .046). We found an increased risk of CD in children introduced to gluten after 6 months and a higher risk in children breastfed after 12 months age.

Systematic review: early infant feeding and the prevention of coeliac disease

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. To summarise current knowledge on the possible relationship between early feeding practices and the risk of coeliac disease (CD). 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. 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. 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.

What effect does breastfeeding have on coeliac disease? A systematic review update

ObjectiveTo update the evidence published in a previous systematic review and meta-analysis that compared the effect of breastfeeding on risk of coeliac disease (CD).Material and methodsA systematic review of observational...

The Missing Link

The Missing Link

Quand doit-on introduire le gluten dans l’alimentation des nourrissons ?

Celiac disease (CD) is an auto-immune enteropathy, triggered in genetically predisposed individuals by the ingestion of dietary gluten. Gluten is the alcohol-soluble protein component of the cereals wheat, rye and barley. CD is a multifactorial condition, originating from the interplay of genetic and environmental factors. The necessary environmental trigger is gluten, while the genetic predisposition has been identified in the major histocompatibility complex region on chromosome 6, with over 90% of CD patients expressing HLA DQ2 and the remaining celiac patients express DQ8. The fact that only about 4 % of DQ2/8-positive individuals exposed to gluten develop CD, has led to the recognition that other genetic and environmental factors are also necessary. In the last few years, several epidemiological studies have suggested that the timing of the introduction of gluten, as well as the pattern of breastfeeding, may play an important role in the subsequent development of CD. Here, we present and review the most recent evidences regarding the effect of timing of gluten introduction during weaning, the amount of gluten introduced and simultaneous breastfeeding, on the development of CD.

Infectious Disease and Risk of Later Celiac Disease in Childhood

The goal was to examine whether parent-reported infection at the time of gluten introduction increases the risk of future celiac disease (CD). Through the population-based All Infants in Southeast Sweden study, parents recorded data on feeding and infectious disease prospectively. Complete data on gluten introduction and breastfeeding duration were available for 9408 children. Those children had 42 826 parent-reported episodes of infectious disease in the first year of life (including 4003 episodes of gastroenteritis). We identified 44 children with biopsy-verified CD diagnosed after 1 year of age, and we used Cox regression to estimate the risk of future CD for children with infection at gluten introduction. Eighteen children with CD (40.9%) had an infection at the time of gluten introduction, compared with 2510 reference individuals (26.8%; P = .035). Few children had gastroenteritis at the time of gluten introduction (1 child with CD [2.3%] vs 166 reference individuals [1.8%]; P = .546). With adjustment for age at gluten introduction and breastfeeding duration, we found no association between a future diagnosis of CD and either any infection (adjusted hazard ratio: 1.8 [95% confidence interval: 0.9-3.6]) or gastroenteritis (adjusted hazard ratio: 2.6 [95% confidence interval: 0.2-30.8]) at the time of gluten introduction. We found no associations between breastfeeding duration, age at gluten introduction, and future CD. These results indicate that parent-reported infection at the time of gluten introduction is not a major risk factor for CD.

Mortality in Celiac Disease, Intestinal Inflammation, and Gluten Sensitivity

CELIAC DISEASE DEVELOPS IN GENETICALLY PREDISposed individuals as a response to ingested gluten. Gluten is the term for the storage proteins of the cereal grains wheat, rye, and barley. While virtually 100% of the population ingests these grains in one form or another and 30% to 40% of the population carry the genetic markers of the disease (HLA-DQ2 or type 8), only 2% to 3% of those with genetic markers develop the disease. This indicates that other genetic factors and environmental precipitants are necessary for disease expression. These factors are largely unknown, although breastfeeding, timing of gluten introduction, and gastrointestinal infections in childhood have been incriminated, at least in the development of childhood celiac disease. The diagnosis of celiac disease is dependent on finding characteristic, although not specific, pathological findings in duodenal biopsies. These changes include inflammatory changes within the small-intestinal epithelium (intraepithelial lymphocytosis) and the lamina propria as well as various degrees of villous atrophy. A range of pathological abnormalities exists, from intraepithelial lymphocytosis with normal villous architecture to total villous atrophy, all of which are considered part of the spectrum of gluten enteropathy or celiac disease. However, there are several causes of intraepithelial lymphocytosis without villous atrophy in addition to celiac disease, such as Helicobacter pylori infection and tropical sprue. It is therefore difficult to diagnose celiac disease in the setting of intestinal inflammation when villous atrophy is absent. But in some clinical settings, such as the presence of symptoms, positive serologic results, and even the appropriate HLA type, patients with these inflammatory changes receive a diagnosis of celiac disease. Serologic blood tests that include antigliadin, tissue transglutaminase (tTG), and endomysial antibodies are used for triaging individuals for endoscopic biopsy. The tTG and endomysial antibodies are sensitive and specific for celiac disease, while antigliadin antibodies are not as sensitive or specific. Celiac disease is common, occurring in about 1% of the population, although the majority of cases are undiagnosed. The number of persons actually diagnosed as having celiac disease varies from country to country, depending on physician awareness of the varied clinical manifestations and the availability of blood tests for the condition. The rate of diagnosis is high in some European countries such as Finland, where in some regions 70% of cases are diagnosed. Within the United States, the rate of diagnosis is increasing, both in adults and children, although only a small fraction (estimated at 5%) of cases are diagnosed. Recent evidence from both Finland and the United States has demonstrated that the prevalence of celiac disease has increased markedly over a relatively short time. In the United States, the prevalence of celiac disease has increased 4-fold in the last 50 years. These data are based on the analysis of stored serum samples and reflect a true increase in the prevalence of the disease, not just the number of individuals who are given diagnoses. The reason for this increase is not clear but may be related to environmental factors such as the changing nature of gluten or other factors related to diet. Accompanying this increase in disease prevalence is a change in the clinical manifestations, so that the classic presentation of diarrhea and malabsorption syndrome is now less common than other presentations. The disease now manifests more often as a multisystem disorder. Anemia, osteoporosis, peripheral neuropathy or ataxia, irritable bowel syndrome, and dyspepsia are all possible presentations. Many patients are asymptomatic, with the disease detected by screening performed because of their presence in a highrisk group such as being a family member or having an associated autoimmune disease, type 1 diabetes, or Down syndrome. Increasingly, those with autoimmune thyroid disease are also screened. Patients with undiagnosed or diagnosed celiac disease appear to have an increased mortality risk. Based on studies that have examined stored serum samples for tTG antibodies and correlated the results with mortality data, those with

Timing of gluten introduction and quantity and nature of gluten-containing foods consumed by infants in Valencia, Spain

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Rotavirus and Celiac Disease: Clues to the Pathogenesis and Perspectives on Prevention

Rotavirus and Celiac Disease: Clues to the Pathogenesis and Perspectives on Prevention

Risk of Celiac Disease Autoimmunity and Timing of Gluten Introduction in the Diet of Infants at Increased Risk of Disease

Risk of Celiac Disease Autoimmunity and Timing of Gluten Introduction in the Diet of Infants at Increased Risk of Disease

Risk of Celiac Disease Autoimmunity and Timing of Gluten Introduction in the Diet of Infants at Increased Risk of Disease

Purpose of the Study. Patients with HLA-DR3 or DR4 alleles are at increased risk for the development of celiac disease. However, not all genetically susceptible individuals develop celiac disease. The objective of this study was to investigate whether there was an association between the timing of exposure to gluten and subsequent development of celiac disease autoimmunity (CDA) in children with a genetic predisposition for celiac disease. Study Population. Children (n = 1560) were identified in the Denver, Colorado, metropolitan area with an increased risk for celiac disease (or type 1 diabetes), defined as having either a first-degree relative with type 1 diabetes or positive cord blood screening for HLA-DR3 or DR4 alleles. This study was conducted over 10 years with a mean follow-up of 4.8 years. Methods. This was a prospective, observational study. Infant diet data were collected during telephone or face-to-face interviews at 3, 6, 9, 12, and 15 months of age. No dietary advice was given to the families. Children had blood drawn at 9, 15, and 24 months and annually thereafter for the measurement of the celiac disease autoantigen, and tissue transglutaminase (tTG). After 1 or 2 positive tTG autoantibody results, small-bowel biopsy was offered to the families, although not all had this procedure performed. The primary outcome of the study was the time to development of CDA defined as the presence of tTG autoantibodies on 2 consecutive results or a positive small-bowel biopsy after a single tTG-positive test. Results. Fifty-one children developed CDA. Children exposed to foods containing wheat, barley, or rye in the first 3 months of life had a 5 times increased odds ratio (P = .02) of CDA as compared with children first exposed to gluten at 4 to 6 months of age. Twenty-five of the CDA-positive children had biopsy-proven celiac disease. In these children, exposure to gluten in the first 3 months of life had a 23 times increased risk (P = .001) of CDA. In the biopsy-proven cohort, children not exposed to gluten until &amp;gt;7 months of age also had a significantly increased risk of CDA (odds ratio: 4; P = .04). There was no association between the development of CDA and the timing of introduction of oats or rice. No protective effect of breastfeeding was found with the development of CDA. Although all children in the cohort were exposed to gluten by 12 months of age, the first positive tTG autoantibody test did not occur until 2 years of age, with a mean age of positive conversion of 4.7 years. Conclusions. In children at increased risk of developing celiac disease, timing of gluten exposure in the diet is associated with the appearance of CDA. Exposure to gluten in the first 3 months of life is thought to be associated with increased risk because of immature or incomplete intestinal barrier function. The authors speculate that late gluten exposure may have been associated with CDA because of greater amounts introduced in the older infants. Reviewer Comments. It is important to understand that this study population was specific children with genetic and family history characteristics at increased risk for the development of celiac disease and may not be generalizable to the entire population. Mean follow-up of this population was just under 5 years, and long-term follow-up of these patients is needed to determine if earlier exposure to gluten simply leads to earlier appearance of CDA and that many (if not all) exposed at-risk children would eventually develop CDA. This study also does not address the relationship between CDA and celiac disease.

Is the timing of infant cereal introduction a risk factor for celiac disease autoimmunity?

Norris JM, Barriga K, Hoffenberg EJ, et al. Risk of celiac disease autoimmunity and timing of gluten introduction in the diet of infants at increased risk of disease. JAMA 2005:293:2343-51. ![Figure][1]</img> Figure. Photo by: E. Wooltorton Background: Celiac disease, or gluten-sensitive

Effect of breast feeding on risk of coeliac disease: a systematic review and meta-analysis of observational studies

Background: Coeliac disease (CD) is a disorder that may depend on genetic, immunological, and environmental factors. Recent observational studies suggest that breast feeding may prevent the development of CD. Aim:...

How important is the timing of gluten introduction for children with celiac disease?

How important is the timing of gluten introduction for children with celiac disease?

Celiac disease: timing of gluten introduction in the infant diet

Celiac disease: timing of gluten introduction in the infant diet

Risk of Celiac Disease Autoimmunity and Timing of Gluten Introduction in the Diet of Infants at Increased Risk of Disease

While gluten ingestion is responsible for the signs and symptoms of celiac disease, it is not known what factors are associated with initial appearance of the disease. To examine whether the timing of gluten exposure in the infant diet was associated with the development of celiac disease autoimmunity (CDA). Prospective observational study conducted in Denver, Colo, from 1994-2004 of 1560 children at increased risk for celiac disease or type 1 diabetes, as defined by possession of either HLA-DR3 or DR4 alleles, or having a first-degree relative with type 1 diabetes. The mean follow-up was 4.8 years. Risk of CDA defined as being positive for tissue transglutaminase (tTG) autoantibody on 2 or more consecutive visits or being positive for tTG once and having a positive small bowel biopsy for celiac disease, by timing of introduction of gluten-containing foods into the diet. Fifty-one children developed CDA. Findings adjusted for HLA-DR3 status indicated that children exposed to foods containing wheat, barley, or rye (gluten-containing foods) in the first 3 months of life (3 [6%] CDA positive vs 40 [3%] CDA negative) had a 5-fold increased risk of CDA compared with children exposed to gluten-containing foods at 4 to 6 months (12 [23%] CDA positive vs 574 [38%] CDA negative) (hazard ratio [HR], 5.17; 95% confidence interval [CI], 1.44-18.57). Children not exposed to gluten until the seventh month or later (36 [71%] CDA positive vs 895 [59%] CDA negative) had a marginally increased risk of CDA compared with those exposed at 4 to 6 months (HR, 1.87; 95% CI, 0.97-3.60). After restricting our case group to only the 25 CDA-positive children who had biopsy-diagnosed celiac disease, initial exposure to wheat, barley, or rye in the first 3 months (3 [12%] CDA positive vs 40 [3%] CDA negative) or in the seventh month or later (19 [76%] CDA positive vs 912 [59%] CDA negative) significantly increased risk of CDA compared with exposure at 4 to 6 months (3 [12%] CDA positive vs 583 [38%] CDA negative) (HR, 22.97; 95% CI, 4.55-115.93; P = .001; and HR, 3.98; 95% CI, 1.18-13.46; P = .04, respectively). Timing of introduction of gluten into the infant diet is associated with the appearance of CDA in children at increased risk for the disease.

This Week in &lt;EMPH&gt;JAMA&lt;/EMPH&gt;

Risk of Celiac Disease Autoimmunity and Timing of Gluten Introduction in the Diet of Infants at Increased Risk of Disease

EFFECT OF BREAST-FEEDING ON RISK OF COELIAC DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS OF OBSERVATIONAL STUDIES

Background: Coeliac disease (CD) is a multifactorial disorder that may depend on genetic, immunological, and environmental factors. Recent observational studies suggest that breast-feeding may prevent the development of CD. Aim: To evaluate articles that compared effects of breast-feeding on risk of CD. Design: Systematic review and meta-analysis of observational studies published between 1966 and June 2004 that examined the association between breast-feeding and the development of CD. Results: Six case-control studies met the inclusion criteria. With the exception of one small study, all the included studies found an association between increasing duration of breast-feeding and decreased risk of developing CD. Meta-analysis showed that the risk of CD was significantly reduced in infants who were being breastfed at the time of gluten introduction (OR 0.48, 95% CI 0.40 to 0.59) compared with infants who were not being breast-fed during this period. Conclusions: Breast-feeding appears to offer some protection against the development of CD. Being breast-fed during the introduction of dietary gluten, and increasing duration of breast-feeding were associated with decreased risk of developing CD. It is, however, not clear from the primary studies whether breast-feeding only delays the onset of symptoms or provides a permanent protection against the disease.