Whether low birth weight (LBW) and preterm delivery (PD) are associated with the risk of developing celiac disease (CD) in children remains unclear. This systematic review and meta-analysis aimed to evaluate the association between LBW and PD with CD development in children.

We searched PubMed, Embase, Scopus, Web of Science, and Google Scholar databases based on the Mesh terms to find observational studies that investigated the association of LBW and PD with CD development in children up to July 18, 2024. This systematic review was based on the PRISMA 2020 checklist. Heterogeneity between studies was assessed with Cochran's Q and I2 tests. Meta-regression was used to control heterogeneity. Publication bias was evaluated using Egger's test. Finally, ten studies involving 3 434 290 participants were included. Based on 10 studies, the pooled prevalence of LBW was 6.4 per 1000 children with CD. A pooled estimate of ten studies did not show a significant relationship between LBW and the risk of developing CD in children [odds ratio (OR): 0.96, 95% confidence interval (CI): 0.76, 1.16, I 2 : 67.9%, P : 0.001). Also, the pooled estimate of six studies did not show a significant relationship between PD and the risk of developing CD in children (OR: 0.98, 95% CI: 0.81, 1.16, I2 : 67.5%, P : 0.001).

We found no evidence of an association between LBW and PD with the risk of developing CD in children.

Celiac disease is an autoimmune condition that affects approximately 1% of the worldwide community. Originally thought to be confined mostly to the small intestine, resulting in villous atrophy and nutrient malabsorption, it has more recently been implicated in systemic manifestations as well, particularly when undiagnosed or left untreated. Herein, the physical and psychological symptoms of celiac disease are described and explored. An emphasis is placed on efforts to query prospective and confirmed celiac disease patients via the use of surveys. Suggestions are made regarding the development of efficacious surveys for the purpose of screening for celiac disease in undiagnosed persons, and monitoring efficacy of the gluten-free diet in persons diagnosed with celiac disease. There are broad categories of physical and psychological symptoms associated with celiac disease. There is also an essential interaction between such physical and the psychological symptoms. It is important to capture the association between symptoms, via queries directed toward suspected and confirmed persons with celiac disease. The use of anonymous online surveys can be helpful to determine the qualities and characteristics which may be associated with this condition. It is suggested that personal surveys should be given a greater role in screening and to lessen the time for diagnosis. Querying the subject directly via a survey can provide clues as to the types of symptoms being experienced by those with celiac disease currently, as well as to determine the salient aspects of the symptomatology, which will be useful for rapid screening and monitoring in future work.

Autoimmune thyroid diseases (AITD) are among the most frequent autoimmune disorders, with a multifactorial etiology in which both genetic and environmental determinants are probably involved. Celiac disease (CeD) also represents a public concern, given its increasing prevalence due to the recent improvement of screening programs, leading to the detection of silent subtypes. The two conditions may be closely associated due to common risk factors, including genetic setting, changes in the composition and diversity of the gut microbiota, and deficiency of nutrients like vitamin D. This comprehensive review discussed the current evidence on the pivotal role of vitamin D in modulating both gut microbiota dysbiosis and immune system dysfunction, shedding light on the possible relevance of an adequate intake of this nutrient in the primary prevention of AITD and CeD. While future technology-based strategies for proper vitamin D supplementation could be attractive in the context of personalized medicine, several issues remain to be defined, including standardized assays for vitamin D determination, timely recommendations on vitamin D intake for immune system functioning, and longitudinal studies and randomized controlled trials to definitely establish a causal relationship between serum vitamin D levels and the onset of AITD and CeD.

There are few reports evaluating different factors, including the severity of duodenal histopathological findings and serological levels of celiac disease (CD), in increasing the probability of thyroid diseases (TD) in adults and children with CD, so, we designed this research.

CD was defined as Marsh type 2 or higher in duodenal histopathology and serological levels of anti-transglutaminase antibodies (anti-tTG) equal to or greater than 18 IU/ml. To assess the likelihood of TD in CD patients, logistic regression analysis was employed.

538 patients were included in this study. Of these, 354 (65.8%) were females and 184 (34.2%) were males. 370 (68.8%) patients were children. Overall, 57 (10.6%) patients had TD, of which 49 (9.1%) had hypothyroidism and 8 (1.5%) had hyperthyroidism. Adults had a significantly higher probability of developing TD than children (OR 1.9; 95% CI 1.1-3.4; P = 0.03). The odds of developing TD were also significantly higher in patients with family marriage in parents (OR 2.3; 95% CI 1.1-4.7; P = 0.03). Other variables such as gastrointestinal symptoms, anti-tTG levels, and severity of Marsh classification did not exhibit a substantial rise in the likelihood of TD development.

The study findings indicated that the likelihood of developing TD in CD patients can be linked to advancing age and having family marriage in parents, while there was no significant association observed with anti-tTG levels, severity of histological damage, and gastrointestinal symptoms.

Antibiotic use is increasing worldwide. However, the use of antibiotics is clearly associated with changes in gut microbiome composition and function, and perturbations have been identified as potential environmental risk factors for chronic inflammatory disorders of the gastrointestinal tract. In this Review, we examine the association between the use of antibiotics and the onset and development of both type 1 and type 2 diabetes, inflammatory bowel disease, including ulcerative colitis and Crohn's disease, as well as coeliac disease and eosinophilic oesophagitis. We discuss the key findings of epidemiological studies, provide mechanistic insights into the pathways by which the gut microbiota might contribute to these diseases, and assess clinical trials investigating the effects of antibiotics. Such studies indicate that antibiotic exposures, varying in type, timing and dosage, could explain differences in disease risk. There seems to be a critical window in early life in which perturbation of the microbiome has a substantial effect on disease development. Identifying the antibiotic-perturbed gut microbiota as a factor that contributes to the pathophysiology of these inflammatory disorders might stimulate new approaches to prevention, diagnosis and treatment.

The effects of early feeding practices on the risk of coeliac disease (CD) remain debated.

To update evidence on these practices on the risk of CD and/or CD-related autoimmunity (CDA), defined as anti-transglutaminase or anti-endomysial antibody positivity METHODS: We searched MEDLINE, EMBASE and the Cochrane Library to May 2022 for randomised controlled trials (RCTs) and observational studies.

We included 36 publications (30 studies). In the population at genetic risk of developing CD (HLA DQ2/DQ8-positive), exclusive or any breastfeeding and longer breastfeeding duration did not reduce the risk of developing CD/CDA during childhood. While a meta-analysis of four case-control studies showed a decreased risk for CD when gluten was introduced during breastfeeding, this was not shown in RCTs and cohort studies. Age at gluten introduction was not associated with cumulative CD/CDA risk, although two RCTs suggested that earlier gluten introduction was associated with earlier CDA appearance. Evidence from six observational studies suggests that consumption of a higher amount of gluten at weaning and/or thereafter may increase CD risk. There is insufficient evidence to determine the amount of gluten associated with an increased CD/CDA risk. Regarding whether infant feeding practices modulate the risk conferred by different HLA genotypes results were inconsistent.

For the population at genetic risk of CD, breastfeeding and age at gluten introduction have no effect on its cumulative incidence during childhood. There is some evidence for an effect of the amount of gluten consumed at weaning and/or thereafter on CD/CDA risk.

Objectives: An observed variation in the risk of celiac disease, according to the season of birth, suggests that vitamin D may affect the development of the disease. The aim of this study was to investigate if vitamin D concentration is associated with the risk of celiac disease autoimmunity (CDA) in genetically at-risk children. Study Design: Children prospectively followed in the multinational The Environmental Determinants of Diabetes in the Young study, conducted at six centers in Europe and the US, were selected for a 1-to-3 nested case-control study. In total, 281 case-control sets were identified. CDA was defined as positivity for tissue transglutaminase autoantibodies (tTGA) on two or more consecutive visits. Vitamin D was measured as 25-hydroxyvitamin D [25(OH)D] concentrations in all plasma samples prior to, and including, the first tTGA positive visit. Conditional logistic regression was used to examine the association between 25(OH)D and risk of CDA. Results: No significant association was seen between 25(OH)D concentrations (per 5 nmol/L increase) and risk for CDA development during early infancy (odds ratio [OR] 0.99, 95% confidence interval [CI] 0.95-1.04) or childhood (OR 1.02, 95% CI 0.97-1.07). When categorizing 25(OH)D concentrations, there was an increased risk of CDA with 25(OH)D concentrations <30 nmol/L (OR 2.23, 95% CI 1.29, 3.84) and >75 nmol/L (OR 2.10, 95% CI 1.28-3.44) in early infancy, as compared with 50-75 nmol/L. Conclusion: This study indicates that 25(OH)D concentrations <30 nmol/L and >75 nmol/L during early infancy were associated with an increased risk of developing CDA in genetically at-risk children. The non-linear relationship raises the need for more studies on the possible role of 25(OH)D in the relation to celiac disease onset.

BACKGROUND Celiac disease is a common disorder but there are few studies comparing the clinical features of the disease in adults, adolescents and children. METHODS Demographic and clinical characteristics of all patients with celiac disease referred to the Celiac Clinic were evaluated and compared in different age groups. RESULTS Of 3416 participants, 473 patients were included. 302 (63.8%) were women and 171 (36.2%) were men. Overall, 325 (68.7%) and 411 (86.9%) patients had gastrointestinal (GI) and non-GI manifestations, respectively. The most common symptom in adults was psychiatric problems (66.5%), while abdominal discomfort was the most common symptom in adolescents (45.2%) and children (53.8%). According to age groups, GI manifestations were seen in 79 (66.4%), 119 (59.8%), and 127 (81.9%) children, adolescents, and adults, respectively. Adults had significantly more GI manifestations than the other groups (PR 1.167; 95% CI: 1.094- 1.244; p < 0.001). Non-GI manifestations were seen in 90 (75.6%), 174 (87.4%), and 147 (94.8%) children, adolescents, and adults, respectively. Adults had significantly more non-GI manifestations than the other groups (PR 1.112; 95% CI: 1.060-1.168; p < 0.001). CONCLUSION Our study showed that there were significant differences in the clinical features of celiac disease between the different age groups. Considering these results may help plan for future studies.

Celiac disease (CD) is a common autoimmune disease with extra-intestinal manifestations, including neurological disorders. There are few reports to assess various factors in increasing the chances of developing neurological disorders in CD, so we designed this study.

All patients with CD at any age who had been referred to the Celiac Clinic were evaluated for neurological problems. CD was defined as IgA anti-transglutaminase antibodies (anti-tTG) of 18 IU/mL or higher in serology and Marsh type I or more severe in histopathological evaluation. Logistic regression analysis was used to evaluate the impact of various independent variables on the neurological manifestations.

A total of 540 patients enrolled in this study. A 360 (66.7%) of patients were children. A 64.8% and 35.2% were female and male, respectively. Overall, 34.1% of patients had neurological manifestation, including headache, neuropathy, epilepsy, and ataxia. The odds of developing neurological manifestations in children were significantly lower than in adults (odds ratio [OR], 0.66; 95% confidence interval [CI], 0.45-0.96; p=0.03) and in patients with gastrointestinal (GI) symptoms significantly higher than in the group without GI manifestations (OR, 1.77; 95% CI, 1.18-2.63; p=0.005). Other variables, including Marsh classification (OR, 0.44; 95% CI, 0.18-1.11; p=0.08) and anti-tTG levels (OR, 1.00; 95% CI, 0.999-1.001; p=0.59) did not significantly increase the chances of developing neurological disorders.

Our study showed that increasing age and the presence of GI symptoms, but not serological and histological findings, could increase the chances of developing neurological diseases in CD patients.

In adults, there is increasing evidence for an association between antibiotic use and gastrointestinal (GI) disorders but in children, the evidence is scarce.

Assess the association between exposure to antibiotics in the first 2 years of life in term born children and the presence of chronic GI disorders later in childhood.

For this systematic review the MEDLINE, Embase, WHO trial register and Web of Science were systematically searched from inception to 8 June 2020. Title and abstract screening (n=12 219), full-text screening (n=132) as well as the quality assessment with the Newcastle-Ottawa Scale were independently performed by two researchers.

The association between antibiotics and inflammatory bowel disease (IBD) (n=6), eosinophilic oesophagitis (EoE) (n=5), coeliac disease (CeD) (n=6), infantile colics (n=3), functional constipation (n=2), recurrent abdominal pain, regurgitation, functional diarrhoea and infant dyschezia were examined.

Twenty-two studies were included, 11 cohort and 11 case-control studies. A best evidence synthesis showed strong evidence for an association between antibiotic exposure in the first 2 years of life and the presence of IBD, and CeD during childhood. Moderate evidence was found for an association with EoE and no association with functional constipation in the first year of life. There was insufficient evidence for the other studied disorders.

The use of antibiotics in early life may increase the risk of GI disorders later in life. Further studies are necessary to unravel the underlying mechanisms and determine potential preventive measures. Meanwhile judicious use of antibiotics in early childhood is highly warranted.

PROSPERO CRD42019132631.

Although genetic predisposition and exposure to dietary gluten are considered necessary triggers for the development of coeliac disease, alterations in the gut microbial composition may also contribute towards the pathogenesis of coeliac disease. This review aims to provide an overview of the available data on the potential mechanisms through which the gut microbiota plays a role in the causation of coeliac disease and to discuss the potential therapeutic strategies that could diminish the consequences of microbial dysbiosis.

A search of the literature was performed using the PubMed, Embase, and JSTOR databases; relevant articles were included.

Recent studies in patients with coeliac disease have reported an increase in the relative amounts of gram negative bacterial genera such as Bacteroides, Prevotella, and Escherichia, and reduced amounts of protective anti-inflammatory bacteria such as Bifidobacteria and Lactobacilli. Dysbiotic microbiota may lead to a dysregulated immune response that may contribute to the pathogenesis of coeliac disease. In infancy, antibiotic use and certain infant feeding practices may lead to alterations in the developing gut microbiota to influence the immune maturation process and predispose to coeliac disease.

The induction of the intestinal immune system and gluten intolerance may be influenced by the relative abundance of certain microbiota. Factors such as infant feeding practices, diet, antibiotics, and infections, may be involved in the development of coeliac disease due to their influence on gut microbial composition. The efficacy of potential modulators of the gut microbiota such as probiotics, prebiotics, and fecal microbial transplant as adjunctive treatments to gluten-free diet in coeliac disease is unproven and requires further investigation.

Beside skeletal system maintenance and protection, possible extra-calcium roles of vitamin D have been recently described. In particular, studies have investigated possible roles of vitamin D as a key modulator of inflammation and immune mechanisms and of the intestinal mucosa barrier. In this regard, vitamin D has been considered as a factor that affects different conditions such as immune-mediated diseases. The new emerging role of vitamin D and its involvement in immune modulation has led it to be considered as a possible key factor involved in celiac disease (CD) onset. CD is a chronic immune-mediated enteropathy of the small intestine that is triggered by dietary gluten protein exposure in individuals who are genetically predisposed. However, along with gluten, other environmental factors are also involved in CD onset. The renewed interest in a molecule that offers great possibilities for new roles has led to an increase in studies, although there remains a lack of studies aimed at contextualizing the role of vitamin D on CD. This review aims to define the possible role of vitamin D in CD onset as it is presently understood, taking into account potential links among vitamin D, the immune system and CD.

There is evidence of a relationship between infection (and the associated antibiotic exposure) and the risk of celiac disease (CD). This study performed a meta-analysis to investigate this relationship.

To identify relevant studies, we conducted systematic searches of the PubMed, Embase, and Cochrane databases for articles published up to April 2019. Random effects models were used to determine overall pooled estimates and 95% confidence intervals (CIs).

The meta-analysis included 19 observational studies (15 on infection and six on antibiotic exposure). Our results showed that any infection was associated with an increased risk of CD later in life (odds ratio, 1.37; 95% CI: 1.2-1.56; P < 0.001). The I² was 94% (high heterogeneity among studies). Subgroup analyses suggested that the risk of CD is not affected by the type of infectious agent, timing of exposure, and site of infection. Exposure to antibiotics was also associated with new-onset CD (odds ratio, 1.2; 95% CI: 1.04-1.39; P < 0.001).

Exposure to early infection or antibiotic appears to increase the odds of developing CD, suggesting that intestinal immune or microbiota dysbiosis may play a role in the pathogenesis of CD. These findings may influence clinical management and primary prevention of CD. However, noncausal explanations for these positive associations cannot be excluded.

The prevalence of celiac disease (CD) has increased significantly in some developed countries in recent decades. Potential risk factors that have been considered in the literature do not appear to provide a convincing explanation for this increase. This has led some researchers to hypothesize that there is a "missing environmental factor" that increases the risk of CD. Based on evidence from the literature, the author proposes that elevation in plasma levels of 1,25-dihydroxyvitamin D [1,25(OH)₂D] is a missing risk factor for CD, and relatedly that significant oral vitamin D exposure is a "missing environmental factor" for CD. First, elevated plasma levels of 1,25(OH)₂D are common in CD, especially in the newly diagnosed. Second, nine distinct conditions that increase plasma levels of 1,25(OH)₂D are either associated with CD or have indications of such an association in the literature. Third, a retrospective study shows that sustained oral vitamin D supplementation in infancy is associated with increased CD risk, and other studies on comorbid conditions support this association. Fourth, large doses of oral vitamin D upregulate many of the same cytokines, chemokines, and toll-like receptors that are upregulated in CD. Fifth, epidemiological evidence, such as the timing of the inception of a CD "epidemic" in Sweden, the increased prevalence of CD in Finland and the United States in recent decades, the unusually low prevalence of CD in Germany, and the differential in prevalence between Finnish Karelians and Russian Karelians, may all be explained by oral vitamin D exposure increasing CD risk. The same is true of some seemingly contradictory results in the literature on the effects of breastfeeding on CD risk. If future research validates this hypothesis, adjustments to oral vitamin D consumption among those who have genetic susceptibility may decrease the risk of CD in these individuals.