| 1. |
- Agardh, Daniel, et al.
(author)
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Clinical Features of Celiac Disease: A Prospective Birth Cohort.
- 2015
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In: Pediatrics. - : American Academy of Pediatrics (AAP). - 1098-4275 .- 0031-4005. ; 135:4, s. 627-634
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Journal article (peer-reviewed)abstract
- To investigate clinical features of celiac disease (CD) and their association with risk factors for CD in a genetic risk birth cohort.
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| 2. |
- Andrén Aronsson, Carin, et al.
(author)
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Age at first introduction to complementary foods is associated with sociodemographic factors in children with increased genetic risk of developing type 1 diabetes.
- 2015
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In: Maternal and Child Nutrition. - : Wiley. - 1740-8709 .- 1740-8695. ; 11:4, s. 803-814
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Journal article (peer-reviewed)abstract
- Infant's age at introduction to certain complementary foods (CF) has in previous studies been associated with islet autoimmunity, which is an early marker for type 1 diabetes (T1D). Various maternal sociodemographic factors have been found to be associated with early introduction to CF. The aims of this study were to describe early infant feeding and identify sociodemographic factors associated with early introduction to CF in a multinational cohort of infants with an increased genetic risk for T1D. The Environmental Determinants of Diabetes in the Young study is a prospective longitudinal birth cohort study. Infants (N = 6404) screened for T1D high risk human leucocyte antigen-DQ genotypes (DR3/4, DR4/4, DR4/8, DR3/3, DR4/4, DR4/1, DR4/13, DR4/9 and DR3/9) were followed for 2 years at six clinical research centres: three in the United States (Colorado, Georgia/Florida, Washington) and three in Europe (Sweden, Finland, Germany). Age at first introduction to any food was reported at clinical visits every third month from the age of 3 months. Maternal sociodemographic data were self-reported through questionnaires. Age at first introduction to CF was primarily associated with country of residence. Root vegetables and fruits were usually the first CF introduced in Finland and Sweden and cereals were usually the first CF introduced in the United States. Between 15% and 20% of the infants were introduced to solid foods before the age of 4 months. Young maternal age (<25 years), low educational level (<12 years) and smoking during pregnancy were significant predictors of early introduction to CF in this cohort. Infants with a relative with T1D were more likely to be introduced to CF later.
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| 3. |
- Andrén Aronsson, Carin, et al.
(author)
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Age at Gluten Introduction and Risk of Celiac Disease.
- 2015
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In: Pediatrics. - : American Academy of Pediatrics (AAP). - 1098-4275 .- 0031-4005. ; 135:2, s. 239-245
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Journal article (peer-reviewed)abstract
- The goal of this study was to determine whether age at introduction to gluten was associated with risk for celiac disease (CD) in genetically predisposed children.
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| 4. |
- Andrén Aronsson, Carin, et al.
(author)
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Association of gluten intake during the first 5 years of life with incidence of celiac disease autoimmunity and celiac disease among children at increased risk
- 2019
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In: JAMA - Journal of the American Medical Association. - : American Medical Association (AMA). - 0098-7484. ; 322:6, s. 514-523
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Journal article (peer-reviewed)abstract
- Importance: High gluten intake during childhood may confer risk of celiac disease. Objectives: To investigate if the amount of gluten intake is associated with celiac disease autoimmunity and celiac disease in genetically at-risk children. Design, Setting, and Participants: The participants in The Environmental Determinants of Diabetes in the Young (TEDDY), a prospective observational birth cohort study designed to identify environmental triggers of type 1 diabetes and celiac disease, were followed up at 6 clinical centers in Finland, Germany, Sweden, and the United States. Between 2004 and 2010, 8676 newborns carrying HLA antigen genotypes associated with type 1 diabetes and celiac disease were enrolled. Screening for celiac disease with tissue transglutaminase autoantibodies was performed annually in 6757 children from the age of 2 years. Data on gluten intake were available in 6605 children (98%) by September 30, 2017. Exposures: Gluten intake was estimated from 3-day food records collected at ages 6, 9, and 12 months and biannually thereafter until the age of 5 years. Main Outcomes and Measures: The primary outcome was celiac disease autoimmunity, defined as positive tissue transglutaminase autoantibodies found in 2 consecutive serum samples. The secondary outcome was celiac disease confirmed by intestinal biopsy or persistently high tissue transglutaminase autoantibody levels. Results: Of the 6605 children (49% females; median follow-up: 9.0 years [interquartile range, 8.0-10.0 years]), 1216 (18%) developed celiac disease autoimmunity and 447 (7%) developed celiac disease. The incidence for both outcomes peaked at the age of 2 to 3 years. Daily gluten intake was associated with higher risk of celiac disease autoimmunity for every 1-g/d increase in gluten consumption (hazard ratio [HR], 1.30 [95% CI, 1.22-1.38]; absolute risk by the age of 3 years if the reference amount of gluten was consumed, 28.1%; absolute risk if gluten intake was 1-g/d higher than the reference amount, 34.2%; absolute risk difference, 6.1% [95% CI, 4.5%-7.7%]). Daily gluten intake was associated with higher risk of celiac disease for every 1-g/d increase in gluten consumption (HR, 1.50 [95% CI, 1.35-1.66]; absolute risk by age of 3 years if the reference amount of gluten was consumed, 20.7%; absolute risk if gluten intake was 1-g/d higher than the reference amount, 27.9%; absolute risk difference, 7.2% [95% CI, 6.1%-8.3%]). Conclusions and Relevance: Higher gluten intake during the first 5 years of life was associated with increased risk of celiac disease autoimmunity and celiac disease among genetically predisposed children.
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| 5. |
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| 6. |
- Andrén Aronsson, Carin, et al.
(author)
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Gluten in infants and celiac disease risk
- 2016
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In: Expert Review of Gastroenterology and Hepatology. - : Informa UK Limited. - 1747-4124 .- 1747-4132. ; 10:6
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Journal article (other academic/artistic)
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| 7. |
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| 8. |
- Beyerlein, Andreas, et al.
(author)
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Intake of Energy and Protein is Associated with Overweight Risk at Age 5.5 Years : Results from the Prospective TEDDY Study
- 2017
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In: Obesity. - : Wiley. - 1930-7381. ; 25:8, s. 1435-1441
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Journal article (peer-reviewed)abstract
- Objective: The associations of energy, protein, carbohydrate, and fat intake with weight status up to the age of 5.5 years were prospectively assessed in The Environmental Determinants of Diabetes in the Young (TEDDY) study. Methods: Food record data (over 3 days) and BMI measurements between 0.25 and 5.5 years were available from 5,563 children with an increased genetic risk for type 1 diabetes followed from shortly after birth. Odds ratios (ORs) were calculated for overweight and obesity by previous intake of energy, protein, carbohydrate, and fat with adjustment for potential confounders. Results: Having overweight or obesity at the age of 5.5 years was positively associated with mean energy intake in previous age intervals (e.g., adjusted OR [95% CI] for overweight: 1.06 [1.04-1.09] per 100 kcal intake at the age of 4.5-5.0 years) and with protein intake after the age of 3.5 and 4.5 years, respectively (e.g., adjusted OR for overweight: 1.06 [1.03-1.09] per 1% of energy intake at the age of 4.5-5.0 years). The respective associations with carbohydrate and fat intake were less consistent. Conclusions: These findings indicate that energy and protein intake are positively associated with increased risk for overweight in childhood but yield no evidence for potential programming effects of protein intake in infancy.
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| 9. |
- Haghighi, Mona, et al.
(author)
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A Comparison of Rule-based Analysis with Regression Methods in Understanding the Risk Factors for Study Withdrawal in a Pediatric Study
- 2016
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Journal article (peer-reviewed)abstract
- Regression models are extensively used in many epidemiological studies to understand the linkage between specific outcomes of interest and their risk factors. However, regression models in general examine the average effects of the risk factors and ignore subgroups with different risk profiles. As a result, interventions are often geared towards the average member of the population, without consideration of the special health needs of different subgroups within the population. This paper demonstrates the value of using rule-based analysis methods that can identify subgroups with heterogeneous risk profiles in a population without imposing assumptions on the subgroups or method. The rules define the risk pattern of subsets of individuals by not only considering the interactions between the risk factors but also their ranges. We compared the rule-based analysis results with the results from a logistic regression model in The Environmental Determinants of Diabetes in the Young (TEDDY) study. Both methods detected a similar suite of risk factors, but the rule-based analysis was superior at detecting multiple interactions between the risk factors that characterize the subgroups. A further investigation of the particular characteristics of each subgroup may detect the special health needs of the subgroup and lead to tailored interventions.
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| 10. |
- Hummel, Sandra, et al.
(author)
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First infant formula type and risk of islet autoimmunity in the environmental determinants of diabetes in the young (TEDDY) study
- 2017
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In: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 40:3, s. 398-404
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Journal article (peer-reviewed)abstract
- OBJECTIVE Studies on the introduction of infant formulas and its effect on the risk of islet autoimmunity and type 1 diabetes (T1D) have yielded inconsistent results. We investigated whether the introduction of formula based on hydrolyzed cow'smilk as the first formula is associated with reduced islet autoimmunity risk in a large prospective cohort. RESEARCH DESIGN AND METHODS The Environmental Determinants of Diabetes in the Young (TEDDY) study prospectively monitors 8,676 children at increased genetic risk for T1D. Autoantibodies to insulin, GAD65, and IA2 were measured regularly to define islet autoimmunity. Information on formula feeding was collected by questionnaires at 3 months of age. RESULTS In survival analyses, after adjustment for family history with T1D, HLA genotype, sex, country, delivery mode, breast-feeding 3 months, and seasonality of birth, we observed no significant association with islet autoimmunity in infants who received extensively hydrolyzed compared with nonhydrolyzed cow'smilk-based formula as the first formula during the first 3 months (adjusted hazard ratio 1.38 [95% CI 0.95; 2.01]), and a significantly increased risk for extensively hydrolyzed formula introduced during the first 7 days (adjusted hazard ratio 1.57 [1.04; 2.38]). Using a partially hydrolyzed or other formula as the first formula, or no formula, was not associated with islet autoimmunity risk. CONCLUSIONS These results add to the existing evidence that islet autoimmunity risk is not reduced, and may be increased, by using hydrolyzed compared with nonhydrolyzed cow's milk-based infant formula as the first formula in infants at increased genetic risk for T1D .
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| 11. |
- Håkansson, Åsa, et al.
(author)
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Effects of lactobacillus plantarum and lactobacillus paracasei on the peripheral immune response in children with celiac disease autoimmunity : A randomized, double-blind, placebo-controlled clinical trial
- 2019
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In: Nutrients. - : MDPI AG. - 2072-6643. ; 11:8
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Journal article (peer-reviewed)abstract
- Two Lactobacillus strains have proven anti-inflammatory properties by reducing pro-inflammatory responses to antigens. This randomized double-blind placebo-controlled trial tested the hypothesis that L. plantarum HEAL9 and L. paracasei 8700:2 suppress ongoing celiac disease autoimmunity in genetically at risk children on a gluten-containing diet in a longitudinally screening study for celiac disease. Seventy-eight children with celiac disease autoimmunity participated of whom 40 received 1010 CFU/day of L. plantarum HEAL9 and L. paracasei 8700:2 (probiotic group) and 38 children maltodextrin (placebo group) for six months. Blood samples were drawn at zero, three and six months and phenotyping of peripheral blood lymphocytes and IgA and IgG autoantibodies against tissue transglutaminase (tTG) were measured. In the placebo group, naïve CD45RA+ Th cells decreased (p = 0.002) whereas effector and memory CD45RO+ Th cells increased (p = 0.003). In contrast, populations of cells expressing CD4+CD25high CD45RO+CCR4+ increased in the placebo group (p = 0.001). Changes between the groups were observed for NK cells (p = 0.038) and NKT cells (p = 0.008). Median levels of IgA-tTG decreased more significantly over time in the probiotic (p = 0.013) than in the placebo (p = 0.043) group whereas the opposite was true for IgG-tTG (p = 0.062 respective p = 0.008). In conclusion, daily oral administration of L. plantarum HEAL9 and L. paracasei 8700:2 modulate the peripheral immune response in children with celiac disease autoimmunity.
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| 12. |
- Hård af Segerstad, Elin M., et al.
(author)
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Daily intake of milk powder and risk of celiac disease in early childhood : A nested case-control study
- 2018
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In: Nutrients. - : MDPI AG. - 2072-6643. ; 10:5
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Journal article (peer-reviewed)abstract
- Milk powder and gluten are common components in Swedish infants’ diets. Whereas large intakes of gluten early in life increases the risk of celiac disease in genetically at-risk Swedish children, no study has yet evaluated if intake of milk powder by 2 years of age is associated with celiac disease. A 1-to-3 nested case-control study, comprised of 207 celiac disease children and 621 controls matched for sex, birth year, and HLA genotype, was performed on a birth cohort of HLA-DR3-DQ2 and/or DR4-DQ8-positive children. Subjects were screened annually for celiac disease using tissue transglutaminase autoantibodies (tTGA). Three-day food records estimated the mean intake of milk powder at ages 6 months, 9 months, 12 months, 18 months, and 24 months. Conditional logistic regression calculated odds ratios (OR) at last intake prior to seroconversion of tTGA positivity, and for each time-point respectively and adjusted for having a first-degree relative with celiac disease and gluten intake. Intake of milk powder prior to seroconversion of tTGA positivity was not associated with celiac disease (OR = 1.00; 95% CI = 0.99, 1.03; p = 0.763). In conclusion, intake of milk powder in early childhood is not associated with celiac disease in genetically susceptible children.
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| 13. |
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| 14. |
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| 15. |
- Johnson, Randi K., et al.
(author)
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Metabolite-related dietary patterns and the development of islet autoimmunity
- 2019
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1
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Journal article (peer-reviewed)abstract
- The role of diet in type 1 diabetes development is poorly understood. Metabolites, which reflect dietary response, may help elucidate this role. We explored metabolomics and lipidomics differences between 352 cases of islet autoimmunity (IA) and controls in the TEDDY (The Environmental Determinants of Diabetes in the Young) study. We created dietary patterns reflecting pre-IA metabolite differences between groups and examined their association with IA. Secondary outcomes included IA cases positive for multiple autoantibodies (mAb+). The association of 853 plasma metabolites with outcomes was tested at seroconversion to IA, just prior to seroconversion, and during infancy. Key compounds in enriched metabolite sets were used to create dietary patterns reflecting metabolite composition, which were then tested for association with outcomes in the nested case-control subset and the full TEDDY cohort. Unsaturated phosphatidylcholines, sphingomyelins, phosphatidylethanolamines, glucosylceramides, and phospholipid ethers in infancy were inversely associated with mAb+ risk, while dicarboxylic acids were associated with an increased risk. An infancy dietary pattern representing higher levels of unsaturated phosphatidylcholines and phospholipid ethers, and lower sphingomyelins was protective for mAb+ in the nested case-control study only. Characterization of this high-risk infant metabolomics profile may help shape the future of early diagnosis or prevention efforts. © 2019, The Author(s).
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| 16. |
- Joslowski, Gesa, et al.
(author)
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Development of a harmonized food grouping system for between-country comparisons in the TEDDY Study
- 2017
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In: Journal of Food Composition and Analysis. - : Elsevier BV. - 0889-1575. ; 63, s. 79-88
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Journal article (peer-reviewed)abstract
- The Environmental Determinants of Diabetes in the Young (TEDDY) is an international study aiming to investigate associations between dietary and other environmental factors and the risk of developing islet autoimmunity and type 1 diabetes. Dietary intake was assessed using a 24-h recall and repeated 3-day food records and analyzed using country-specific food composition databases (FCDBs) in Finland, Germany, Sweden, and the U.S. with respective in-house calculation programs. A food grouping harmonization process between four country-specific FCDBs was conducted to evaluate and achieve comparability on food group definitions and quantification of food consumption across the countries. Systematic review revealed that the majority of existing food groups of the TEDDY FCDBs were not comparable. Therefore, a completely new classification system of 15 mutually exclusive main food groups (e.g. vegetables) and 89 subgroups (e.g. root vegetables, leafy vegetables) was developed. Foods and beverages were categorized into basic foods (single ingredient) and composite dishes (multiple ingredients). Composite dishes were broken down to ingredients using food composition data available in the FCDBs or generic recipes created for the harmonization effort. The daily consumption of every food group across FCDBs was quantified consistently as either raw or prepared weight depending on the food group to achieve maximal comparability.
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| 17. |
- Krischer, Jeffrey P, et al.
(author)
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Predicting Islet Cell Autoimmunity and Type 1 Diabetes : An 8-Year TEDDY Study Progress Report
- 2019
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In: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 42:6, s. 1051-1060
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Assessment of the predictive power of The Environmental Determinants of Diabetes in the Young (TEDDY)-identified risk factors for islet autoimmunity (IA), the type of autoantibody appearing first, and type 1 diabetes (T1D).RESEARCH DESIGN AND METHODS: A total of 7,777 children were followed from birth to a median of 9.1 years of age for the development of islet autoantibodies and progression to T1D. Time-dependent sensitivity, specificity, and receiver operating characteristic (ROC) curves were calculated to provide estimates of their individual and collective ability to predict IA and T1D.RESULTS: HLA genotype (DR3/4 vs. others) was the best predictor for IA (Youden's index J = 0.117) and single nucleotide polymorphism rs2476601, in PTPN22, was the best predictor for insulin autoantibodies (IAA) appearing first (IAA-first) (J = 0.123). For GAD autoantibodies (GADA)-first, weight at 1 year was the best predictor (J = 0.114). In a multivariate model, the area under the ROC curve (AUC) was 0.678 (95% CI 0.655, 0.701), 0.707 (95% CI 0.676, 0.739), and 0.686 (95% CI 0.651, 0.722) for IA, IAA-first, and GADA-first, respectively, at 6 years. The AUC of the prediction model for T1D at 3 years after the appearance of multiple autoantibodies reached 0.706 (95% CI 0.649, 0.762).CONCLUSIONS: Prediction modeling statistics are valuable tools, when applied in a time-until-event setting, to evaluate the ability of risk factors to discriminate between those who will and those who will not get disease. Although significantly associated with IA and T1D, the TEDDY risk factors individually contribute little to prediction. However, in combination, these factors increased IA and T1D prediction substantially.
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| 18. |
- Lundgren, Markus, et al.
(author)
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Analgesic antipyretic use among young children in the TEDDY study : No association with islet autoimmunity
- 2017
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In: BMC Pediatrics. - : Springer Science and Business Media LLC. - 1471-2431. ; 17:1
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Journal article (peer-reviewed)abstract
- Background: The use of analgesic antipyretics (ANAP) in children have long been a matter of controversy. Data on their practical use on an individual level has, however, been scarce. There are indications of possible effects on glucose homeostasis and immune function related to the use of ANAP. The aim of this study was to analyze patterns of analgesic antipyretic use across the clinical centers of The Environmental Determinants of Diabetes in the Young (TEDDY) prospective cohort study and test if ANAP use was a risk factor for islet autoimmunity. Methods: Data were collected for 8542 children in the first 2.5 years of life. Incidence was analyzed using logistic regression with country and first child status as independent variables. Holm's procedure was used to adjust for multiplicity of intercountry comparisons. Time to autoantibody seroconversion was analyzed using a Cox proportional hazards model with cumulative analgesic use as primary time dependent covariate of interest. For each categorization, a generalized estimating equation (GEE) approach was used. Results: Higher prevalence of ANAP use was found in the U.S. (95.7%) and Sweden (94.8%) compared to Finland (78.1%) and Germany (80.2%). First-born children were more commonly given acetaminophen (OR 1.26; 95% CI 1.07, 1.49; p = 0.007) but less commonly Non-Steroidal Anti-inflammatory Drugs (NSAID) (OR 0.86; 95% CI 0.78, 0.95; p = 0.002). Acetaminophen and NSAID use in the absence of fever and infection was more prevalent in the U.S. (40.4%; 26.3% of doses) compared to Sweden, Finland and Germany (p < 0.001). Acetaminophen or NSAID use before age 2.5 years did not predict development of islet autoimmunity by age 6 years (HR 1.02, 95% CI 0.99-1.09; p = 0.27). In a sub-analysis, acetaminophen use in children with fever weakly predicted development of islet autoimmunity by age 3 years (HR 1.05; 95% CI 1.01-1.09; p = 0.024). Conclusions: ANAP use in young children is not a risk factor for seroconversion by age 6 years. Use of ANAP is widespread in young children, and significantly higher in the U.S. compared to other study sites, where use is common also in absence of fever and infection.
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| 19. |
- Pitchika, Anitha, et al.
(author)
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Associations of Maternal Diabetes During Pregnancy with Overweight in Offspring : Results from the Prospective TEDDY Study
- 2018
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In: Obesity. - : Wiley. - 1930-7381 .- 1930-739X. ; 26:9, s. 1457-1466
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Journal article (peer-reviewed)abstract
- Objective: This study aimed to determine the relationship between different forms of, and potential pathways between, maternal diabetes and childhood obesity at different ages. Methods: Prospective cohort data from The Environmental Determinants of Diabetes in the Young (TEDDY) study, which was composed of 5,324 children examined from 0.25 to 6 years of age, were analyzed. Cross-sectional and longitudinal analyses taking into account potential confounders and effect modifiers such as maternal prepregnancy BMI and birth weight z scores were performed. Results: Offspring of mothers with gestational diabetes mellitus (GDM) or type 1 diabetes mellitus (T1DM) showed a higher BMI standard deviation score and increased risk for overweight and obesity at 5.5 years of age than offspring of mothers without diabetes. While these associations could be substantially explained by maternal prepregnancy BMI in offspring of mothers with GDM, significant associations disappeared after adjustment for birth weight z scores in offspring of T1DM mothers. Furthermore, overweight risk became stronger with increasing age in offspring of mothers with diabetes compared with offspring of mothers without diabetes. Conclusions: Maternal diabetes is associated with increased risk of offspring overweight, and the association appears to get stronger as children grow older. Indeed, intrauterine exposure to maternal T1DM may predispose children to later obesity through increased birth weight, while maternal BMI is more important in children exposed to GDM.
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| 20. |
- Riikonen, Anne, et al.
(author)
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Milk feeding and first complementary foods during the first year of life in the TEDDY study
- 2018
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In: Maternal and Child Nutrition. - : Wiley. - 1740-8695 .- 1740-8709. ; 14:4
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Journal article (peer-reviewed)abstract
- The aim was to describe milk feeding patterns and first weaning foods during the first year of life in a large prospective birth cohort of infants with increased genetic risk for Type 1 diabetes (T1D) recruited in 4 different countries: the United States, Finland, Germany, and Sweden. All enrolled children with dietary information (n = 8,673) were included in the analyses; 1,307 (15%) children who dropped out before the first birthday were excluded from some analyses. Supplementary milk feeding in the first 3 days of life was common in all the four countries, although the type of the supplementary milk differed by country and by maternal T1D. Donated human milk was commonly used only in Finland. In all the countries, the most common first supplementary food was cow's milk-based infant formula, especially among offspring of mothers with T1D. The use of specific types of infant formulas differed notably by country: Extensively hydrolysed formulas were most used in Finland, partially hydrolysed ones in the United States and in Germany, and soy formulas only in the United States. Infant formulas commonly included probiotics, prebiotics, and starches. During the first year of life, most of the infants received conventional cow's milk. Overall, milk feeding during the first 3 days of life and thereafter until the first birthday differed markedly by maternal T1D status and across countries. These descriptive data may be useful in understanding early infant feeding practices and in planning potential interventions, which affect infant feeding.
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| 21. |
- Smith, Laura B., et al.
(author)
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Psychological manifestations of celiac disease autoimmunity in young children
- 2017
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In: Pediatrics. - : American Academy of Pediatrics (AAP). - 0031-4005 .- 1098-4275. ; 139:3
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Journal article (peer-reviewed)abstract
- BACKGROUND AND OBJECTIVES: Psychological symptoms can be associated with celiac disease; abstract however, this association has not been studied prospectively in a pediatric cohort. We examined mother report of psychological functioning in children persistently positive for tissue transglutaminase autoantibodies (tTGA), defined as celiac disease autoimmunity (CDA), compared with children without CDA in a screening population of genetically at-risk children. We also investigated differences in psychological symptoms based on mothers' awareness of their child's CDA status. METHODS: The Environmental Determinants of Diabetes in the Young study followed 8676 children to identify triggers of type 1 diabetes and celiac disease. Children were tested for tTGA beginning at 2 years of age. The Achenbach Child Behavior Checklist assessed child psychological functioning at 3.5 and 4.5 years of age. RESULTS: At 3.5 years, 66 mothers unaware their child had CDA reported more child anxiety and depression, aggressive behavior, and sleep problems than 3651 mothers of children without CDA (all Ps ≤ .03). Unaware-CDA mothers also reported more child anxiety and depression, withdrawn behavior, aggressive behavior, and sleep problems than 440 mothers aware of their child's CDA status (all Ps ≤.04). At 4.5 years, there were no differences. CONCLUSIONS: In 3.5-year-old children, CDA is associated with increased reports of child depression and anxiety, aggressive behavior, and sleep problems when mothers are unaware of their child's CDA status. Mothers' knowledge of their child's CDA status is associated with fewer reports of psychological symptoms, suggesting that awareness of the child's tTGA test results affects reporting of symptoms.
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| 22. |
- Törn, Carina, et al.
(author)
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Complement gene variants in relation to autoantibodies to beta cell specific antigens and type 1 diabetes in the TEDDY Study
- 2016
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Journal article (peer-reviewed)abstract
- A total of 15 SNPs within complement genes and present on the ImmunoChip were analyzed in The Environmental Determinants of Diabetes in the Young (TEDDY) study. A total of 5474 subjects were followed from three months of age until islet autoimmunity (IA: n = 413) and the subsequent onset of type 1 diabetes (n = 115) for a median of 73 months (IQR 54-91). Three SNPs within ITGAM were nominally associated (p < 0.05) with IA: rs1143678 [Hazard ratio; HR 0.80; 95% CI 0.66-0.98; p = 0.032], rs1143683 [HR 0.80; 95% CI 0.65-0.98; p = 0.030] and rs4597342 [HR 1.16; 95% CI 1.01-1.32; p = 0.041]. When type 1 diabetes was the outcome, in DR3/4 subjects, there was nominal significance for two SNPs: rs17615 in CD21 [HR 1.52; 95% CI 1.05-2.20; p = 0.025] and rs4844573 in C4BPA [HR 0.63; 95% CI 0.43-0.92; p = 0.017]. Among DR4/4 subjects, rs2230199 in C3 was significantly associated [HR 3.20; 95% CI 1.75-5.85; p = 0.0002, uncorrected] a significance that withstood Bonferroni correction since it was less than 0.000833 (0.05/60) in the HLA-specific analyses. SNPs within the complement genes may contribute to IA, the first step to type 1 diabetes, with at least one SNP in C3 significantly associated with clinically diagnosed type 1 diabetes.
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| 23. |
- Uusitalo, Ulla, et al.
(author)
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Association of Early Exposure of Probiotics and Islet Autoimmunity in the TEDDY Study.
- 2015
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In: JAMA Pediatrics. - : American Medical Association (AMA). - 2168-6211 .- 2168-6203. ; 170:1, s. 20-28
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Journal article (peer-reviewed)abstract
- Probiotics have been hypothesized to affect immunologic responses to environmental exposures by supporting healthy gut microbiota and could therefore theoretically be used to prevent the development of type 1 diabetes mellitus (T1DM)-associated islet autoimmunity.
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| 24. |
- Uusitalo, Ulla, et al.
(author)
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Early infant diet and islet autoimmunity in the TEDDY study
- 2018
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In: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 41:3, s. 522-530
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Journal article (peer-reviewed)abstract
- OBJECTIVE To examine duration of breastfeeding and timing of complementary foods and risk of islet autoimmunity (IA). RESEARCH DESIGN AND METHODS The Environmental Determinants of Diabetes in the Young (TEDDY) study prospectively follows 8,676 childrenwith increased genetic risk of type 1 diabetes (T1D) in the U.S., Finland, Germany, and Sweden. This study included 7,563 children with at least 9 months of follow-up. Blood samples were collected every 3 months from birth to evaluate IA, defined as persistent, confirmed positive antibodies to insulin (IAAs), GAD, or insulinoma antigen-2. We examined the associations between diet and the risk of IA using Cox regression models adjusted for country, T1D family history, HLA genotype, sex, and early probiotic exposure. Additionally, we investigated martingale residuals and log-rank statistics to determine cut points for ages of dietary exposures. RESULTS Later introduction of glutenwas associatedwith increased risk of any IA and IAA. The hazard ratios (HRs) for every 1-month delay in gluten introduction were 1.05 (95% CI 1.01, 1.10; P = 0.02) and 1.08 (95% CI 1.00, 1.16; P = 0.04), respectively. Martingale residual analysis suggested that the age at gluten introduction could be grouped as <4, 4-9, and >9 months. The risk of IA associated with introducing gluten before 4months of age was lower (HR 0.68; 95% CI 0.47, 0.99), and the risk of IA associated with introducing it later than the age of 9 months was higher (HR 1.57; 95% CI 1.07, 2.31) than introduction between 4 and 9 months of age. CONCLUSIONS The timing of gluten-containing cereals and IA should be studied further.
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- Uusitalo, Ulla, et al.
(author)
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Early probiotic supplementation and the risk of celiac disease in children at genetic risk
- 2019
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In: Nutrients. - : MDPI AG. - 2072-6643. ; 11:8
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Journal article (peer-reviewed)abstract
- Probiotics are linked to positive regulatory effects on the immune system. The aim of the study was to examine the association between the exposure of probiotics via dietary supplements or via infant formula by the age of 1 year and the development of celiac disease autoimmunity (CDA) and celiac disease among a cohort of 6520 genetically susceptible children. Use of probiotics during the first year of life was reported by 1460 children. Time-to-event analysis was used to examine the associations. Overall exposure of probiotics during the first year of life was not associated with either CDA (n = 1212) (HR 1.15; 95%CI 0.99, 1.35; p = 0.07) or celiac disease (n = 455) (HR 1.11; 95%CI 0.86, 1.43; p = 0.43) when adjusting for known risk factors. Intake of probiotic dietary supplements, however, was associated with a slightly increased risk of CDA (HR 1.18; 95%CI 1.00, 1.40; p = 0.043) compared to children who did not get probiotics. It was concluded that the overall exposure of probiotics during the first year of life was not associated with CDA or celiac disease in children at genetic risk.
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