| 1. |
- Haghighi, Mona, et al.
(författare)
-
A Comparison of Rule-based Analysis with Regression Methods in Understanding the Risk Factors for Study Withdrawal in a Pediatric Study
- 2016
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
-
Tidskriftsartikel (refereegranskat)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.
|
|
| 2. |
- Kemppainen, Kaisa M, et al.
(författare)
-
Association Between Early-Life Antibiotic Use and the Risk of Islet or Celiac Disease Autoimmunity
- 2017
-
Ingår i: JAMA Pediatrics. - : American Medical Association (AMA). - 2168-6211 .- 2168-6203. ; 171:12, s. 1217-1225
-
Tidskriftsartikel (refereegranskat)abstract
- Importance: Evidence is lacking regarding the consequences of antibiotic use in early life and the risk of certain autoimmune diseases.Objective: To test the association between early-life antibiotic use and islet or celiac disease (CD) autoimmunity in genetically at-risk children prospectively followed up for type 1 diabetes (T1D) or CD.Design, Setting, and Participants: HLA-genotyped newborns from Finland, Germany, Sweden, and the United States were enrolled in the prospective birth cohort of The Environmental Determinants of Diabetes in the Young (TEDDY) study between November 20, 2004, and July 8, 2010. The dates of analysis were November 20, 2004, to August 31, 2014. Individuals from the general population and those having a first-degree relative with T1D were enrolled if they had 1 of 9 HLA genotypes associated with a risk for T1D.Exposures: Parental reports of the most common antibiotics (cephalosporins, penicillins, and macrolides) used between age 3 months and age 4 years were recorded prospectively.Main Outcomes and Measures: Islet autoimmunity and CD autoimmunity were defined as being positive for islet or tissue transglutaminase autoantibodies at 2 consecutive clinic visits at least 3 months apart. Hazard ratios and 95% CIs calculated from Cox proportional hazards regression models were used to assess the relationship between antibiotic use in early life before seroconversion and the development of autoimmunity.Results: Participants were 8495 children (49.0% female) and 6558 children (48.7% female) enrolled in the TEDDY study who were tested for islet and tissue transglutaminase autoantibodies, respectively. Exposure to and frequency of use of any antibiotic assessed in this study in early life or before seroconversion did not influence the risk of developing islet autoimmunity or CD autoimmunity. Cumulative use of any antibiotic during the first 4 years of life was not associated with the appearance of any autoantibody (hazard ratio [HR], 0.98; 95% CI, 0.95-1.01), multiple islet autoantibodies (HR, 0.99; 95% CI, 0.95-1.03), or the transglutaminase autoantibody (HR, 1.00; 95% CI, 0.98-1.02).Conclusions and Relevance: The use of the most prescribed antibiotics during the first 4 years of life, regardless of geographic region, was not associated with the development of autoimmunity for T1D or CD. These results suggest that a risk of islet or tissue transglutaminase autoimmunity need not influence the recommendations for clinical use of antibiotics in young children at risk for T1D or CD.
|
|
| 3. |
- Krischer, Jeffrey P., et al.
(författare)
-
The 6 year incidence of diabetes-associated autoantibodies in genetically at-risk children: the TEDDY study
- 2015
-
Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 58:5, s. 980-987
-
Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis Islet autoantibodies, in addition to elevated blood glucose, define type 1 diabetes. These autoantibodies are detectable for a variable period of time before diabetes onset. Thus, the occurrence of islet autoantibodies is associated with the beginning of the disease process. The age at, and order in, which autoantibodies appear may be associated with different genetic backgrounds or environmental exposures, or both. Methods Infants with HLA-DR high-risk genotypes (DR3/4, DR4/4, DR4/8 and DR3/3) were enrolled and prospectively followed with standardised autoantibody assessments quarterly throughout the first 4 years of life and then semi-annually thereafter. Results Autoantibodies appeared in 549/8,503 (6.5%) children during 34,091 person-years of follow-up. Autoantibodies at 3 (0.1%) and 6 (0.2%) months of age were rare. Of the 549, 43.7% had islet autoantibodies to insulin (IAA) only, 37.7% had glutamic acid decarboxylase autoantibodies (GADA) only, 13.8% had both GADA and IAA only, 1.6% had insulinoma antigen-2 only and 3.1% had other combinations. The incidence of IAA only peaked within the first year of life and declined over the following 5 years, but GADA only increased until the second year and remained relatively constant. GADA only were more common than IAA only in HLA-DR3/3 children but less common in HLA-DR4/8 children. Conclusions/interpretation Islet autoantibodies can occur very early in life and the order of appearance was related to HLA-DR-DQ genotype.
|
|
| 4. |
- Lundgren, Markus, et al.
(författare)
-
Analgesic antipyretic use among young children in the TEDDY study : No association with islet autoimmunity
- 2017
-
Ingår i: BMC Pediatrics. - : Springer Science and Business Media LLC. - 1471-2431. ; 17:1
-
Tidskriftsartikel (refereegranskat)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.
|
|
| 5. |
- Lynch, Kristian F., et al.
(författare)
-
Gestational respiratory infections interacting with offspring HLA and CTLA-4 modifies incident β-cell autoantibodies
- 2018
-
Ingår i: Journal of Autoimmunity. - : Elsevier BV. - 0896-8411. ; 86, s. 93-103
-
Tidskriftsartikel (refereegranskat)abstract
- β-cell autoantibodies against insulin (IAA), GAD65 (GADA) and IA-2 (IA-2A) precede onset of childhood type 1 diabetes (T1D). Incidence of the first appearing β-cell autoantibodies peaks at a young age and is patterned by T1D-associated genes, suggesting an early environmental influence. Here, we tested if gestational infections and interactions with child's human leukocyte antigen (HLA) and non-HLA genes affected the appearance of the first β-cell autoantibody. Singletons of mothers without diabetes (n = 7472) with T1D-associated HLA-DR-DQ genotypes were prospectively followed quarterly through the first 4 years of life, then semiannually until age 6 years, using standardized autoantibody analyses. Maternal infections during pregnancy were assessed via questionnaire 3-4.5 months post-delivery. Polymorphisms in twelve non-HLA genes associated with the first appearing β-cell autoantibodies were included in a Cox regression analysis. IAA predominated as the first appearing β-cell autoantibody in younger children (n = 226, median age at seroconversion 1.8 years) and GADA (n = 212; 3.2 years) in children aged ≥2 years. Gestational infections were not associated with the first appearing β-cell autoantibodies overall. However, gestational respiratory infections (G-RI) showed a consistent protective influence on IAA (HR 0.64, 95% CI 0.45-0.91) among CTLA4-(AG, GG) children (G-RI*. CTLA4 interaction, p = 0.002). The predominant associations of HLA-DR-DQ 4-8/8-4 with IAA and HLA-DR-DQ 3-2/3-2 with GADA were not observed if a G-RI was reported (G-RI*HLA-DR-DQ interaction, p = 0.03). The role of G-RI may depend on offspring HLA and CTLA-4 alleles and supports a bidirectional trigger for IAA or GADA as a first appearing β-cell autoantibody in early life.
|
|
| 6. |
- Yang, Jimin, et al.
(författare)
-
Factors associated with longitudinal food record compliance in a paediatric cohort study.
- 2015
-
Ingår i: Public Health Nutrition. - 1475-2727. ; :Jun 19, s. 1-10
-
Tidskriftsartikel (refereegranskat)abstract
- Non-compliance with food record submission can induce bias in nutritional epidemiological analysis and make it difficult to draw inference from study findings. We examined the impact of demographic, lifestyle and psychosocial factors on such non-compliance during the first 3 years of participation in a multidisciplinary prospective paediatric study.
|
|
| 7. |
- Elding Larsson, Helena, et al.
(författare)
-
Pandemrix® vaccination is not associated with increased risk of islet autoimmunity or type 1 diabetes in the TEDDY study children
- 2018
-
Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 61:1, s. 193-202
-
Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis: During the A/H1N1 2009 (A/California/04/2009) pandemic, mass vaccination with a squalene-containing vaccine, Pandemrix®, was performed in Sweden and Finland. The vaccination was found to cause narcolepsy in children and young adults with the HLA-DQ 6.2 haplotype. The aim of this study was to investigate if exposure to Pandemrix® similarly increased the risk of islet autoimmunity or type 1 diabetes. Methods: In The Environmental Determinants of Diabetes in the Young (TEDDY) study, children are followed prospectively for the development of islet autoimmunity and type 1 diabetes. In October 2009, when the mass vaccination began, 3401 children at risk for islet autoimmunity and type 1 diabetes were followed in Sweden and Finland. Vaccinations were recorded and autoantibodies against insulin, GAD65 and insulinoma-associated protein 2 were ascertained quarterly before the age of 4 years and semi-annually thereafter. Results: By 5 August 2010, 2413 of the 3401 (71%) children observed as at risk for an islet autoantibody or type 1 diabetes on 1 October 2009 had been vaccinated with Pandemrix®. By 31 July 2016, 232 children had at least one islet autoantibody before 10 years of age, 148 had multiple islet autoantibodies and 96 had developed type 1 diabetes. The risk of islet autoimmunity was not increased among vaccinated children. The HR (95% CI) for the appearance of at least one islet autoantibody was 0.75 (0.55, 1.03), at least two autoantibodies was 0.85 (0.57, 1.26) and type 1 diabetes was 0.67 (0.42, 1.07). In Finland, but not in Sweden, vaccinated children had a lower risk of islet autoimmunity (0.47 [0.29, 0.75]), multiple autoantibodies (0.50 [0.28, 0.90]) and type 1 diabetes (0.38 [0.20, 0.72]) compared with those who did not receive Pandemrix®. The analyses were adjusted for confounding factors. Conclusions/interpretation: Children with an increased genetic risk for type 1 diabetes who received the Pandemrix® vaccine during the A/H1N1 2009 pandemic had no increased risk of islet autoimmunity, multiple islet autoantibodies or type 1 diabetes. In Finland, the vaccine was associated with a reduced risk of islet autoimmunity and type 1 diabetes.
|
|
| 8. |
- Hummel, Sandra, et al.
(författare)
-
Associations of breastfeeding with childhood autoimmunity, allergies, and overweight : The Environmental Determinants of Diabetes in the Young (TEDDY) study
- 2021
-
Ingår i: The American journal of clinical nutrition. - : Elsevier BV. - 1938-3207 .- 0002-9165. ; 114:1, s. 134-142
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Breastfeeding has beneficial effects on numerous health outcomes.OBJECTIVES: We investigated whether breastfeeding duration is associated with the development of early childhood autoimmunity, allergies, or obesity in a multinational prospective birth cohort.METHODS: Infants with genetic susceptibility for type 1 diabetes (n = 8676) were followed for the development of autoantibodies to islet autoantigens or transglutaminase, allergies, and for anthropometric measurements to a median age of 8.3 y (IQR: 2.8-10.2 y). Information on breastfeeding was collected at 3 mo of age and prospectively thereafter. A propensity score for longer breastfeeding was calculated from the variables that were likely to influence any or exclusive breastfeeding. The risks of developing autoimmunity or allergy were assessed using Cox proportional hazards models, and the risk of obesity at 5.5 y of age was assessed using logistic regression with adjustment by the propensity score.RESULTS: Breastfeeding duration was not associated with a lower risk of either islet or transglutaminase autoimmunity (any breastfeeding >6 mo, adjusted HR: 1.07; 95% CI: 0.96, 1.19; exclusive breastfeeding >3 mo, adjusted HR: 1.03; 95% CI: 0.92, 1.15). Exclusive breastfeeding >3 mo was associated with a decreased risk of seasonal allergic rhinitis (adjusted HR: 0.70; 95% CI: 0.53, 0.92; P < 0.01). Any breastfeeding >6 mo and exclusive breastfeeding >3 mo were associated with decreased risk of obesity (adjusted OR: 0.62; 95% CI: 0.47, 0.81; P < 0.001; and adjusted OR: 0.68; 95% CI: 0.47, 0.95; P < 0.05, respectively).CONCLUSIONS: Longer breastfeeding was not associated with a lower risk of childhood (islet or transglutaminase) autoimmunity in genetically at-risk children but was associated with decreased risk of seasonal allergic rhinitis and obesity at 5.5 y of age.
|
|
| 9. |
- Johnson, Suzanne Bennett, et al.
(författare)
-
First-appearing islet autoantibodies for type 1 diabetes in young children : maternal life events during pregnancy and the child's genetic risk
- 2021
-
Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 64:3, s. 591-602
-
Tidskriftsartikel (refereegranskat)abstract
- AIMS/HYPOTHESIS: Psychological stress has long been considered a possible trigger of type 1 diabetes, although prospective studies examining the link between psychological stress or life events during pregnancy and the child's type 1 diabetes risk are rare. The objective of this study was to examine the association between life events during pregnancy and first-appearing islet autoantibodies (IA) in young children, conditioned by the child's type 1 diabetes-related genetic risk.METHODS: The IA status of 7317 genetically at-risk The Environmental Determinants of Diabetes in the Young (TEDDY) participants was assessed every 3 months from 3 months to 4 years, and bi-annually thereafter. Reports of major life events during pregnancy were collected at study inception when the child was 3 months of age and placed into one of six categories. Life events during pregnancy were examined for association with first-appearing insulin (IAA) (N = 222) or GAD (GADA) (N = 209) autoantibodies in the child until 6 years of age using proportional hazard models. Relative excess risk due to interaction (RERI) by the child's HLA-DR and SNP profile was estimated.RESULTS: Overall, 65% of mothers reported a life event during pregnancy; disease/injury (25%), serious interpersonal (28%) and job-related (25%) life events were most common. The association of life events during pregnancy differed between IAA and GADA as the first-appearing autoantibody. Serious interpersonal life events correlated with increased risk of GADA-first only in HLA-DR3 children with the BACH2-T allele (HR 2.28, p < 0.0001), an additive interaction (RERI 1.87, p = 0.0004). Job-related life events were also associated with increased risk of GADA-first among HLA-DR3/4 children (HR 1.53, p = 0.04) independent of serious interpersonal life events (HR 1.90, p = 0.002), an additive interaction (RERI 1.19, p = 0.004). Job-related life events correlated with reduced risk of IAA-first (HR 0.55, p = 0.004), particularly in children with the BTNL2-GG allele (HR 0.48; 95% CI 0.31, 0.76).CONCLUSIONS/INTERPRETATION: Specific life events during pregnancy are differentially related to IAA vs GADA as first-appearing IA and interact with different HLA and non-HLA genetic factors, supporting the concept of different endotypes underlying type 1 diabetes. However, the mechanisms underlying these associations remain to be discovered. Life events may be markers for other yet-to-be-identified factors important to the development of first-appearing IA.
|
|
| 10. |
- Kemppainen, Kaisa M, et al.
(författare)
-
Factors That Increase Risk of Celiac Disease Autoimmunity After a Gastrointestinal Infection in Early Life
- 2017
-
Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier BV. - 1542-3565. ; 15:5, s. 5-702
-
Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Little is known about the pathogenic mechanisms of gluten immunogenicity in patients with celiac disease. We studied temporal associations between infections and the development of celiac disease autoimmunity, and examined effects of HLA alleles, rotavirus vaccination status, and infant feeding. Methods: We monitored 6327 children in the United States and Europe carrying HLA risk genotypes for celiac disease from 1 to 4 years of age for presence of tissue transglutaminase autoantibodies (the definition of celiac disease autoimmunity), until March 31, 2015. Parental reports of gastrointestinal and respiratory infections were collected every third month from birth. We analyzed time-varying relationships among reported infections, rotavirus vaccination status, time to first introduction of gluten, breastfeeding, and risk of celiac disease autoimmunity using proportional hazard models. Results: We identified 13,881 gastrointestinal infectious episodes (GIE) and 79,816 respiratory infectious episodes. During the follow-up period, 732 of 6327 (11.6%) children developed celiac disease autoimmunity. A GIE increased the risk of celiac disease autoimmunity within the following 3 months by 33% (hazard ratio [HR], 1.33; 95% confidence interval [CI], 1.11-1.59). This risk increased 2-fold among children born in winter and introduced to gluten before age 6 months (HR, 2.08; 95% CI, 1.46-2.98), and increased 10-fold among children without HLA-DQ2 alleles and breastfed for fewer than 4 months (HR, 9.76; 95% CI, 3.87-24.8). Risk of celiac disease autoimmunity was reduced in children vaccinated against rotavirus and introduced to gluten before age 6 months (HR, 0.57; 95% CI, 0.36-0.88). Conclusions: Gastrointestinal infections increase the risk of celiac disease autoimmunity in children with genetic susceptibility to this autoimmune disorder. The risk is modified by HLA genotype, infant gluten consumption, breastfeeding, and rotavirus vaccination, indicating complex interactions among infections, genetic factors, and diet in the etiology of celiac disease in early childhood.
|
|
