Functional metagenomic analysis reveals potential inflammatory triggers associated with genetic risk for autoimmune disease.

To assess functional differences between the microbiomes of individuals with autoimmune risk-associated human leukocyte antigen (HLA) genetics and autoimmune protection-associated HLA, we performed a metagenomic analysis of stool samples from 72 infants in the All Babies in Southeast Sweden general-population cohort and assessed haplotype-peptide binding affinities. Infants with risk-associated HLA DR3-DQ2.5 and DR4-DQ8 had a higher abundance of known pathogen-associated molecular patterns and virulence related genes than infants with protection-associated HLA DR15-DQ6.2. However, there was limited overlap in the type of inflammatory trigger between risk groups. Supported by a high Firmicutes/Bacteroides ratio and differentially abundant flagellated species, genes related to the synthesis of flagella were prominent in those with HLA DR3-DQ2.5. However, this haplotype had a significantly lower likelihood of binding affinity to flagellin peptides. O-antigen biosynthesis genes were significantly correlated with the risk genotypes and absent from protective genotype association, supported by the differential abundance of gram-negative bacteria seen in the risk-associated groups. Genes related to vitamin B biosynthesis stood out in higher abundance in infants with HLA DR3-DQ2.5/DR4-DQ8 heterozygosity compared to those with autoimmune-protective genetics. Prevotella species and genus were significantly abundant in all infant groups with high risk for autoimmune disease. The potential inflammatory triggers associated with genetic risk for autoimmunity have significant implications. These results suggest that certain HLA haplotypes may be creating the opportunity for dysbiosis and subsequent inflammation early in life by clearing beneficial microbes or not clearing proinflammatory microbes. This HLA gatekeeping may prevent genetically at-risk individuals from benefiting from probiotic therapies by restricting the colonization of those beneficial bacteria.

Early environmental predictors for attention-deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD) and their co-occurrence: The prospective ABIS-Study.

ADHD and ASD are highly heritable and show a high co-occurrence and persistence into adulthood. This study aimed to identify pre and perinatal risk factors, and early psychosocial exposures related to later diagnosis of ADHD, ASD, and their co-occurrence. 16,365 children born 1997-1999 and their families, involved in the prospective population-based ABIS study (All Babies in Southeast Sweden), were included in this sub-study. Pre and perinatal factors and early environmental psychosocial exposures were collected from parental-questionnaires at birth and 1-year follow-up. Diagnoses from birth up to 23 years of age were obtained from the Swedish National Diagnosis Register in 2020. The cumulative incidence of ADHD, ASD, and their co-occurrence in the ABIS-cohort Study were 4.6%, 1.7%, and 1.1%, respectively. Being male was associated with an increased risk for ADHD, ASD, and their co-occurrence (aOR 1.30, 1.56, and 1.91, respectively), while higher household income reduced it (aOR 0.82, 0.73, and 0.64). Serious life events during pregnancy (aOR 1.40) and maternal smoking (aOR 1.51) increased the risk of ADHD, while older maternal age (aOR 0.96), higher parental education (aOR 0.72 maternal and aOR 0.74 paternal) and longer exclusive breastfeeding (aOR 0.72) reduced it. Non-Swedish paternal nationality (aOR 0.40) and higher maternal education (aOR 0.74) were associated with a lower risk of ASD, while a family history of autoimmune diseases increased the risk of the co-occurrence of both disorders (aOR 1.62). Obtained results suggest that the etiology of ADHD, ASD, and their co-occurrence is independently associated with environmental psychosocial predictors. The co-occurrence seems to overlap the etiology of ADHD, in which psychosocial determinants have a larger role, however, it is also independently influenced by a family history of autoimmune diseases.

HbA1c and the risk of developing peripheral neuropathy in childhood-onset type 1 diabetes: A follow-up study over 3 decades.

AIMS: We have evaluated long-term weighted mean HbA1c (wHbA1c), HbA1c variability, diabetes duration, and lipid profiles in relation to the development of diabetic peripheral neuropathy (DPN), nephropathy, and retinopathy in childhood-onset type 1 diabetes. MATERIALS AND METHODS: In a longitudinal cohort study, 49 patients (21 women) with childhood-onset type 1 diabetes were investigated with neurophysiological measurements, blood tests, and clinical examinations after a diabetes duration of 7.7 (±3.3) years (baseline) and followed with repeated examinations for 30.6 (±5.2) years. We calculated wHbA1c by integrating the area under all HbA1c values since the diabetes diagnosis. Lipid profiles were analysed in relation to the presence of DPN. Long-term fluctuations of HbA1c variability were computed as the standard deviation of all HbA1c measurements. Data regarding the presence of other diabetes complications were retrieved from medical records. RESULTS: In this follow-up study, 51% (25/49) of the patients fulfilled electrophysiological criteria for DPN. In nerve conduction studies, there was a deterioration in the amplitudes and conduction velocities for the median, peroneal, and sural nerves over time. Patients with DPN had a longer duration of diabetes, higher wHbA1c, and increased HbA1c variability. The lowest wHbA1c value associated with the development of DPN was 62 mmol/mol (7.8%). The presence of albuminuria and retinopathy was positively correlated with the presence of neuropathy. CONCLUSIONS: More than half of the patients had developed DPN after 30 years. None of the patients who developed DPN had a wHbA1c of less than 62 mmol/mol (7.8%).

Early family socioeconomic status and asthma-related outcomes in school-aged children: Results from seven birth cohort studies.

OBJECTIVE: To examine the associations between maternal education and household income during early childhood with asthma-related outcomes in children aged 9-12 years in the UK, the Netherlands, Sweden, Australia, the USA and Canada. METHODS: Data on 31 210 children were obtained from 7 prospective birth cohort studies across six countries. Asthma-related outcomes included ever asthma, wheezing/asthma attacks and medication control for asthma. Relative social inequalities were estimated using pooled risk ratios (RRs) adjusted for potential confounders (child age, sex, mother ethnic background and maternal age) for maternal education and household income. The Slope Index of Inequality (SII) was calculated for each cohort to evaluate absolute social inequalities. RESULTS: Ever asthma prevalence ranged from 8.3% (Netherlands) to 29.1% (Australia). Wheezing/asthma attacks prevalence ranged from 3.9% (Quebec) to 16.8% (USA). Pooled RRs for low (vs high) maternal education and low (vs high) household income were: ever asthma (education 1.24, 95% CI 1.13 to 1.37; income 1.28, 95% CI 1.15 to 1.43), wheezing/asthma attacks (education 1.14, 95% CI 0.97 to 1.35; income 1.22, 95% CI 1.03 to 1.44) and asthma with medication control (education 1.16, 95% CI 0.97 to 1.40; income 1.25, 95% CI 1.01 to 1.55). SIIs supported the lower risk for children with more highly educated mothers and those from higher-income households in most cohorts, with few exceptions. CONCLUSIONS: Social inequalities by household income on the risk of ever asthma, wheezing/asthma attacks, and medication control for asthma were evident; the associations were attenuated for maternal education. These findings support the need for prevention policies to address the relatively high risks of respiratory morbidity in children in families with low socioeconomic status.

Partial Clinical Remission of Type 1 Diabetes in Swedish Children: A Longitudinal Study from the Swedish National Quality Register (SWEDIABKIDS) and the Better Diabetes Diagnosis (BDD) Study.

Aims/Hypotheses: To investigate the frequency and characteristics of partial remission in Swedish children with type 1 diabetes and whether the insulin delivery method, that is, continuous subcutaneous insulin infusion (CSII) or multiple daily injections (MDIs), affects incidence and duration of this period, 2007-2011. Factors that increase the proportion of subjects who enter partial remission and extend this period can improve long-term metabolic control and reduce the risk of severe hypoglycemia, improve quality of life, and, in the long run, reduce late complications. Methods: Longitudinal data from 2007 to 2020 were extracted from the Swedish National Quality Register (SWEDIABKIDS) with all reported newly diagnosed children. Data on C-peptide from the participants in the Better Diabetes Diagnosis study from 2007 to 2010 were used. The definition of partial remission was insulin dose-adjusted HbA1c: HbA1c (%) + [4 × total daily insulin dose (U/kg/day)] ≤9. Results: Of the 3887 patients, 56% were boys. More boys than girls were in partial remission throughout the follow-up period until 24 months after diabetes onset. Fewer children 0-6 years old had partial remission at 3 and 12 months but not at 24 months compared with older age-groups. A larger proportion of patients using CSII at 12 and 24 months remained in partial remission compared with those with MDI (37% vs. 33%, P = 0.02 and 31% vs. 27%, P = 0.01, respectively). The level of C-peptide was higher in the group with partial remission and mean HbA1c was lower (both P < 0.001). Partial remission at 12 months after diabetes onset was associated with CSII (odds ratio [OR]: 1.39, confidence interval [CI]:1.13, 1.71), shorter diabetes duration (OR: 0.80, CI: 0.76, 0.84), and male sex (OR: 1.23, CI: 1.04, 1.46). Conclusions/Interpretation: Insulin through MDI, longer duration of diabetes, and female sex were associated with lower frequency of partial remission. Use of CSII seems to contribute to longer partial remission among Swedish children with type 1 diabetes.

Development of a clinical calculator to aid the identification of MODY in pediatric patients at the time of diabetes diagnosis.

Maturity Onset Diabetes of the Young (MODY) is a young-onset, monogenic form of diabetes without needing insulin treatment. Diagnostic testing is expensive. To aid decisions on who to test, we aimed to develop a MODY probability calculator for paediatric cases at the time of diabetes diagnosis, when the existing "MODY calculator" cannot be used. Firth logistic regression models were developed on data from 3541 paediatric patients from the Swedish 'Better Diabetes Diagnosis' (BDD) population study (n = 46 (1.3%) MODY (HNF1A, HNF4A, GCK)). Model performance was compared to using islet autoantibody testing. HbA1c, parent with diabetes, and absence of polyuria were significant independent predictors of MODY. The model showed excellent discrimination (c-statistic = 0.963) and calibrated well (Brier score = 0.01). MODY probability > 1.3% (ie. above background prevalence) had similar performance to being negative for all 3 antibodies (positive predictive value (PPV) = 10% v 11% respectively i.e. ~ 1 in 10 positive test rate). Probability > 1.3% and negative for 3 islet autoantibodies narrowed down to 4% of the cohort, and detected 96% of MODY cases (PPV = 31%). This MODY calculator for paediatric patients at time of diabetes diagnosis will help target genetic testing to those most likely to benefit, to get the right diagnosis.

Breastfeeding Duration Is Not Associated With Offspring Inflammatory Bowel Disease Risk in Three Population-Based Birth Cohorts.

BACKGROUND & AIMS: Breastfeeding is critical for offspring health and development. Although many observational studies report a protective effect between breastfeeding and inflammatory bowel disease (IBD), the relationship is not well-understood. METHODS: We used prospectively collected data from 3 population-based birth cohorts (Danish National Birth Cohort, Norwegian Mother, Father, and Child Cohort, and All Babies in Southeast Sweden) and cross-linked national registers to ascertain the impact of breastfeeding duration on offspring IBD risk in each country, using adjusted Cox proportional regression analyses. We performed meta-analyses to determine pooled estimates. RESULTS: We included 148,737 offspring and 169,510 offspring in analyses of exclusive and any breastfeeding duration, respectively. During median follow-up of 16.3-22.3 years, between 1996 and 2021, 543 offspring were diagnosed with IBD. In each country, there was no association between exclusive breastfeeding duration and offspring IBD risk after adjusting for birth year (Denmark), offspring sex, parental IBD status, maternal education, smoking during pregnancy, age at delivery, mode of delivery, preterm birth, and small for gestational age. The pooled adjusted hazard ratio for IBD was 1.24 (95% confidence interval, 0.94-1.62; Q = 0.16, I2 = 0.0%) and 1.02 (95% confidence interval, 0.85-1.21; Q = 1.45, I 2= 0.0%) among offspring breastfed exclusively for ≥6 months and <4 months, respectively, compared with 4-5 months. Similarly, we found null associations in pooled analyses of any breastfeeding duration and IBD, subtypes Crohn's disease and ulcerative colitis, as well as in cohort-specific analyses. CONCLUSIONS: In prospectively collected data from 3 population-based birth cohorts, the duration of exclusive or any breastfeeding was not associated with offspring IBD risk.

Early increase in HbA1c trajectory predicts development of severe microangiopathy in patients with type 1 diabetes: the VISS study.

INTRODUCTION: To study the HbA1c trajectory from the time of diagnosis to examine if patients at the greatest risk for severe microangiopathy can be identified early allowing clinicians to intervene as soon as possible to avoid complications. RESEARCH DESIGN AND METHODS: In a population-based observational study, 447 patients diagnosed with type 1 diabetes before 35 years of age, 1983-1987, were followed from diagnosis until 2019. Mean HbA1c was calculated each year for each patient. Severe diabetic microangiopathy was defined as proliferative diabetic retinopathy (PDR) or macroalbuminuria (nephropathy). RESULTS: After 32 years, 27% had developed PDR and 8% macroalbuminuria. Patients with weighted HbA1c (wHbA1c); <57 mmol/mol; <7.4% did not develop PDR or macroalbuminuria. The HbA1c trajectories for patients developing PDR and macroalbuminuria follow separate courses early on and stay separated for 32 years during the follow-up. Patients without severe complications show an initial dip, after which HbA1c slowly increases. HbA1c in patients with severe complications directly rises to a high level within a few years. Mean HbA1c calculated for the period 5-8 years after diabetes onset strongly predicts the development of severe complications. Females with childhood-onset diabetes exhibit a high peak in HbA1c during adolescence associated with higher wHbA1c and higher prevalence of PDR. CONCLUSIONS: The HbA1c trajectory from diabetes onset shows that mean HbA1c for the period 5-8 years after diagnosis strongly predicts severe microangiopathy. Females with childhood-onset diabetes exhibit a high peak in HbA1c during adolescence associated with higher wHbA1c and a higher prevalence of PDR.

Infant microbes and metabolites point to childhood neurodevelopmental disorders.

This study has followed a birth cohort for over 20 years to find factors associated with neurodevelopmental disorder (ND) diagnosis. Detailed, early-life longitudinal questionnaires captured infection and antibiotic events, stress, prenatal factors, family history, and more. Biomarkers including cord serum metabolome and lipidome, human leukocyte antigen (HLA) genotype, infant microbiota, and stool metabolome were assessed. Among the 16,440 Swedish children followed across time, 1,197 developed an ND. Significant associations emerged for future ND diagnosis in general and for specific ND subtypes, spanning intellectual disability, speech disorder, attention-deficit/hyperactivity disorder, and autism. This investigation revealed microbiome connections to future diagnosis as well as early emerging mood and gastrointestinal problems. The findings suggest links to immunodysregulation and metabolism, compounded by stress, early-life infection, and antibiotics. The convergence of infant biomarkers and risk factors in this prospective, longitudinal study on a large-scale population establishes a foundation for early-life prediction and intervention in neurodevelopment.

Time spent outdoors in childhood related to myopia among young adults in the Swedish ABIS cohort.

PURPOSE: Elucidate the prevalence of myopia among young adults from a birth cohort of Swedish children and its relationship to possible risk factors during their childhood. METHODS: Five thousand two hundred young adults, mean 23.4 years and 58% females, participating in the prospective birth cohort All Babies in Southeast Sweden (ABIS) answered a questionnaire including questions regarding health and physical activity, spectacle use, myopia and age at first optical correction. Questionnaires at previous follow-ups at ages 2-3, 5-6 and 8 years included information on type of housing, time outdoors, screen time and hours of reading. Myopia prevalence and associations with potential risk factors were analysed in univariate and multivariate regression models with Bonferroni's correction of p-values. RESULTS: In the ABIS Swedish birth cohort of young adults, the prevalence of myopia was 29%. A univariate logistic regression showed a higher odds ratio for myopia with female gender (OR 1.59; p < 0.05) and a completed and started university education (OR 1.52; p < 0.05). Significantly lower odds ratios were found for hours spent outdoors at 8 years of age (OR 0.82; p < 0.05). Multivariate logistic regression showed a higher odds ratio for myopia in females (OR 1.52-1.57; p < 0.05) and completed and started university education (OR 1.34-1.49; p < 0.05) in all models. In a model including accommodative effort, measured in diopter hours at 8 years of age, hours spent outdoors were associated with a lower odds ratio for myopia (OR 0.86; p < 0.05). No association could be detected between myopia and the type of housing or near work. CONCLUSION: The prevalence of myopia among young adults in a Swedish birth cohort was lower or unchanged compared to previous data. Female gender, higher education and less time spent outdoors in childhood were associated with an increased risk of developing myopia. Recommendations from child health services and schools should be given to stimulate children to spend enough time outdoors.

Prenatal exposure to environmental contaminants and cord serum metabolite profiles in future immune-mediated diseases.

BACKGROUND: Prenatal exposure to environmental contaminants is a significant health concern because it has the potential to interfere with host metabolism, leading to adverse health effects in early childhood and later in life. Growing evidence suggests that genetic and environmental factors, as well as their interactions, play a significant role in the development of autoimmune diseases. OBJECTIVE: In this study, we hypothesized that prenatal exposure to environmental contaminants impacts cord serum metabolome and contributes to the development of autoimmune diseases. METHODS: We selected cord serum samples from All Babies in Southeast Sweden (ABIS) general population cohort, from infants who later developed one or more autoimmune-mediated and inflammatory diseases: celiac disease (CD), Crohn's disease (IBD), hypothyroidism (HT), juvenile idiopathic arthritis (JIA), and type 1 diabetes (T1D) (all cases, N = 62), along with matched controls (N = 268). Using integrated exposomics and metabolomics mass spectrometry (MS) based platforms, we determined the levels of environmental contaminants and metabolites. RESULTS: Differences in exposure levels were found between the controls and those who later developed various diseases. High contaminant exposure levels were associated with changes in metabolome, including amino acids and free fatty acids. Specifically, we identified marked associations between metabolite profiles and exposure levels of deoxynivalenol (DON), bisphenol S (BPS), and specific per- and polyfluorinated substances (PFAS). IMPACT STATEMENT: Abnormal metabolism is a common feature preceding several autoimmune and inflammatory diseases. However, few studies compared common and specific metabolic patterns preceding these diseases. Here we hypothesized that exposure to environmental contaminants impacts cord serum metabolome, which may contribute to the development of autoimmune diseases. We found differences in exposure levels between the controls and those who later developed various diseases, and importantly, on the metabolic changes associated with the exposures. High contaminant exposure levels were associated with specific changes in metabolome. Our study suggests that prenatal exposure to specific environmental contaminants alters the cord serum metabolomes, which, in turn, might increase the risk of various immune-mediated diseases.

Atopic Dermatitis in Early Childhood and Risk of Inflammatory Bowel Disease: A Scandinavian Birth Cohort Study.

OBJECTIVE: To examine the association between early-life atopic manifestations and later risk of inflammatory bowel disease (IBD), for which prospective data are scarce. STUDY DESIGN: The population-based All Babies in Southeast Sweden (ABIS) and Norwegian Mother, Father, and Child (MoBa) cohorts follow children from birth (ABIS 1997-1999; MoBa 2000-2009) to the end of 2021. Based on validated questionnaires, parents prospectively reported information on asthma, food-related allergic symptoms, atopic dermatitis, and allergic rhinitis by age 3. IBD was defined by ≥ 2 diagnostic records in the national health registries. Cox regression estimated hazard ratios adjusted (aHRs) for parental IBD, atopy, education level, smoking habits, and national origin. Cohort-specific estimates were pooled using a random-effects model. RESULTS: We compiled data on 83 311 children (ABIS, n = 9041; MoBa, n = 74 270). In over 1 174 756 person-years of follow-up, 301 participants were diagnosed with IBD. Children with atopic dermatitis at age 3 had an increased risk of IBD (pooled aHR = 1.46 [95% CI = 1.13-1.88]), Crohn's disease (pooled aHR = 1.53 [95%CI = 1.04-2.26]), and ulcerative colitis (pooled aHR = 1.78 [95%CI = 1.15-2.75]). Conversely, any atopic manifestation by age 3 was not associated with IBD (pooled aHR = 1.20 [95%CI = 0.95-1.52]), nor were analyses specifically focused on early-life food-related allergic symptoms, asthma, and allergic rhinitis. CONCLUSION: While atopic manifestations in early childhood were overall not associated with IBD, children with atopic dermatitis specifically were at increased risk of developing IBD, suggesting shared etiologic traits; these findings might be useful in identifying at-risk individuals for IBD.

Breastfeeding decreases the risk of developing psoriasis through to early adulthood.

BACKGROUND: Psoriasis is a genetically determined systemic skin disease, although environmental trigger factors are required for disease manifestation. Some of these triggers, such as stress, infections and drug exposure, have been identified. OBJECTIVES: To explore the role of early nutrition as a risk factor for the development of psoriasis. METHODS: Parents in the All Babies in Southeast Sweden (ABIS) prospective birth cohort (n = 16 415) answered questionnaires at birth and when their children were aged 1 and 3 years. A diagnosis of psoriasis was determined from the Swedish National Patient Register and National Drug Prescription Register. Statistical analyses were conducted using custom-written R scripts. RESULTS: Individuals breastfed for < 4 months and who received infant formula before 4 months of age had a higher risk of psoriasis [odds ratio (OR) 1.84 (P = 0.02) and OR 1.88 (P = 0.02), respectively]. At the 3-year follow-up, the increased consumption of fish, especially from the Baltic Sea, increased the risk of psoriasis (OR 9.61; P = 0.003). In addition, the risk of psoriasis increased following the consumption of a large volume of milk (OR 2.53; P = 0.04). CONCLUSIONS: Our study underscores, for the first time, the impact of very early nutrition on the manifestation of psoriasis through early adulthood. Exclusive breastfeeding for 4 months appears to be protective.

Predictive biomarkers of rapidly developing insulin deficiency in children with type 1 diabetes.

INTRODUCTION: The rate of progression to complete insulin deficiency varies greatly in type 1 diabetes. This constitutes a challenge, especially when randomizing patients in intervention trials aiming to preserve beta cell function. This study aimed to identify biomarkers predictive of either a rapid or slow disease progression in children with new-onset type 1 diabetes. RESEARCH DESIGN AND METHODS: A retrospective, longitudinal cohort study of children (<18 years) with type 1 diabetes (N=46) was included at diagnosis and followed until complete insulinopenia (C-peptide <0.03 nmol/L). Children were grouped into rapid progressors (n=20, loss within 30 months) and slow progressors (n=26). A sex-matched control group of healthy children (N=45) of similar age was included for comparison. Multiple biomarkers were assessed by proximity extension assay (PEA) at baseline and follow-up. RESULTS: At baseline, rapid progressors had lower C-peptide and higher autoantibody levels than slow. Three biomarkers were higher in the rapid group: carbonic anhydrase 9, corticosteroid 11-beta-dehydrogenase isozyme 1, and tumor necrosis factor receptor superfamily member 21. In a linear mixed model, 25 proteins changed over time, irrespective of group. One protein, a coxsackievirus B-adenovirus receptor (CAR) increased over time in rapid progressors. Eighty-one proteins differed between type 1 diabetes and healthy controls. Principal component analysis could not distinguish between rapid, slow, and healthy controls. CONCLUSIONS: Despite differences in individual proteins, the combination of multiple biomarkers analyzed by PEA could not distinguish the rate of progression in children with new-onset type 1 diabetes. Only one marker was altered significantly when considering both time and group effects, namely CAR, which increased significantly over time in the rapid group. Nevertheless, we did find some markers that may be useful in predicting the decline of the C-peptide. Moreover, these could potentially be important for understanding type 1 diabetes pathogenesis.

Prevalence and Predictive Factors for Celiac Disease in Children With Type 1 Diabetes: Whom and When to Screen? A Nationwide Longitudinal Cohort Study of Swedish Children.

OBJECTIVE: To examine the prevalence and predictive factors for celiac disease (CD) after a diagnosis of type 1 diabetes (T1D) in children and adolescents, to improve the current screening guidelines. RESEARCH DESIGN AND METHODS: The association between sex, age at T1D diagnosis, HLA, and diabetes autoantibodies, and a diagnosis of CD was examined in 5,295 children with T1D from the Better Diabetes Diagnosis study in Sweden. RESULTS: The prevalence of biopsy-proven CD was 9.8%, of which 58.2% already had a CD diagnosis before or at T1D onset. Almost all, 95.9%, were diagnosed with CD within 5 years after the T1D diagnosis. Younger age at the T1D diagnosis and being homozygote for DQ2 increased the risk of CD after T1D, but neither sex nor diabetes-related autoantibodies were associated with the risk. CONCLUSIONS: Age at and time after diabetes diagnosis should be considered in screening guidelines for CD in children with T1D.

Assisting the implementation of screening for type 1 diabetes by using artificial intelligence on publicly available data.

The type 1 diabetes community is coalescing around the benefits and advantages of early screening for disease risk. To be accepted by healthcare providers, regulatory authorities and payers, screening programmes need to show that the testing variables allow accurate risk prediction and that individualised risk-informed monitoring plans are established, as well as operational feasibility, cost-effectiveness and acceptance at population level. Artificial intelligence (AI) has the potential to contribute to solving these issues, starting with the identification and stratification of at-risk individuals. ASSET (AI for Sustainable Prevention of Autoimmunity in the Society; www.asset.healthcare ) is a public/private consortium that was established to contribute to research around screening for type 1 diabetes and particularly to how AI can drive the implementation of a precision medicine approach to disease prevention. ASSET will additionally focus on issues pertaining to operational implementation of screening. The authors of this article, researchers and clinicians active in the field of type 1 diabetes, met in an open forum to independently debate key issues around screening for type 1 diabetes and to advise ASSET. The potential use of AI in the analysis of longitudinal data from observational cohort studies to inform the design of improved, more individualised screening programmes was also discussed. A key issue was whether AI would allow the research community and industry to capitalise on large publicly available data repositories to design screening programmes that allow the early detection of individuals at high risk and enable clinical evaluation of preventive therapies. Overall, AI has the potential to revolutionise type 1 diabetes screening, in particular to help identify individuals who are at increased risk of disease and aid in the design of appropriate follow-up plans. We hope that this initiative will stimulate further research on this very timely topic.

Tobacco Smoke Exposure in Early Childhood and Later Risk of Inflammatory Bowel Disease: A Scandinavian Birth Cohort Study.

OBJECTIVES: To examine the association between early-life smoking exposure and later risk of inflammatory bowel disease [IBD]. METHODS: We followed 115663 participants from the Norwegian Mother, Father and Child [MoBa] and All Babies in Southeast Sweden [ABIS] cohorts from birth [1997-2009] through 2021. IBD was identified through national patient registers. Validated questionnaire data defined maternal smoking during pregnancy, maternal environmental tobacco smoke [ETS] exposure during pregnancy, and child ETS exposure by ages 12 and 36 months. Cox regression was used to estimate adjusted hazard ratios [aHRs] for sex, maternal age, education level, parental IBD, and origin. Cohort-specific estimates were pooled using a random-effects model. RESULTS: During 1 987 430 person-years of follow-up, 444 participants developed IBD [ABIS, 112; MoBa, 332]. Any vs no maternal smoking during pregnancy yielded a pooled aHR of 1.30 [95% CI = 0.97-1.74] for offspring IBD. Higher level of maternal smoking during pregnancy (compared with no smoking, average ≥6 cigarettes/day: pooled aHR = 1.60 [95% CI = 1.08-2.38]) was associated with offspring IBD, whereas a lower smoking level was not (average 1-5 cigarettes/day: pooled aHR = 1.09 [95% CI = 0.73-1.64]). Child ETS exposure in the first year of life was associated with later IBD (any vs no ETS, pooled aHR = 1.32 [95% CI = 1.03-1.69]). Estimates observed for child ETS exposure by 36 months were similar but not statistically significant. CONCLUSIONS: In this prospective Scandinavian cohort study, children exposed to higher levels of maternal smoking during pregnancy or ETS during the first year of life were at increased risk of later IBD.