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OBJECTIVES: To investigate the associations of physical activity (PA) and sedentary behaviour in early childhood with asthma and reduced lung function in later childhood within a large collaborative study. DESIGN: Pooling of longitudinal data from collaborating birth cohorts using meta-analysis of separate cohort-specific estimates and analysis of individual participant data of all cohorts combined. SETTING: Children aged 0-18 years from 26 European birth cohorts. PARTICIPANTS: 136 071 individual children from 26 cohorts, with information on PA and/or sedentary behaviour in early childhood and asthma assessment in later childhood. MAIN OUTCOME MEASURE: Questionnaire-based current asthma and lung function measured by spirometry (forced expiratory volume in 1 s (FEV1), FEV1/forced vital capacity) at age 6-18 years. RESULTS: Questionnaire-based and accelerometry-based PA and sedentary behaviour at age 3-5 years was not associated with asthma at age 6-18 years (PA in hours/day adjusted OR 1.01, 95% CI 0.98 to 1.04; sedentary behaviour in hours/day adjusted OR 1.03, 95% CI 0.99 to 1.07). PA was not associated with lung function at any age. Analyses of sedentary behaviour and lung function showed inconsistent results. CONCLUSIONS: Reduced PA and increased sedentary behaviour before 6 years of age were not associated with the presence of asthma later in childhood.

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

OBJECTIVES: To investigate the associations of physical activity (PA) and sedentary behaviour in early childhood with asthma and reduced lung function in later childhood within a large collaborative study. DESIGN: Pooling of longitudinal data from collaborating birth cohorts using meta-analysis of separate cohort-specific estimates and analysis of individual participant data of all cohorts combined. SETTING: Children aged 0-18 years from 26 European birth cohorts. PARTICIPANTS: 136 071 individual children from 26 cohorts, with information on PA and/or sedentary behaviour in early childhood and asthma assessment in later childhood. MAIN OUTCOME MEASURE: Questionnaire-based current asthma and lung function measured by spirometry (forced expiratory volume in 1 s (FEV1), FEV1/forced vital capacity) at age 6-18 years. RESULTS: Questionnaire-based and accelerometry-based PA and sedentary behaviour at age 3-5 years was not associated with asthma at age 6-18 years (PA in hours/day adjusted OR 1.01, 95% CI 0.98 to 1.04; sedentary behaviour in hours/day adjusted OR 1.03, 95% CI 0.99 to 1.07). PA was not associated with lung function at any age. Analyses of sedentary behaviour and lung function showed inconsistent results. CONCLUSIONS: Reduced PA and increased sedentary behaviour before 6 years of age were not associated with the presence of asthma later in childhood.

The composition of human breast milk (HBM) exhibits significant variability both between individuals and within the same individual. While environmental factors are believed to play a role in this variation, their influence on breast milk composition remains inadequately understood. Herein, we investigate the impact of environmental factors on HBM lipid composition in a general population cohort. The study included mothers (All Babies In Southeast Sweden study) whose children later progressed to one or more immune-mediated diseases later in life: type 1 diabetes (n = 9), celiac disease (n = 24), juvenile idiopathic arthritis (n = 9), inflammatory bowel disease (n = 7), hypothyroidism (n = 6), and matched controls (n = 173). Lipidome of HBM was characterized by liquid chromatography combined with high-resolution mass spectrometry. We observed that maternal age, body mass index, diet, and exposure to perfluorinated alkyl substances (PFASs) had a marked impact on breast milk lipidome, with larger changes observed in the milk of those mothers whose children later developed autoimmune diseases. We also observed differences in breast milk lipid composition in those mothers whose offspring later developed autoimmune diseases. Our study suggests that breast milk lipid composition is modified by a complex interaction between genetic and environmental factors, and, importantly, this impact was significantly more pronounced in those mothers whose offspring later developed autoimmune/inflammatory diseases. Our findings also suggest that merely assessing PFAS concentration may not capture the full extent of the impact of chemical exposures; thus, the more comprehensive exposome approach is essential for accurately assessing the impact of PFAS exposure on HBM and, consequently, on the health outcomes of the offspring., This study was supported by the Swedish Research Council (grant nos. and 2020-03674 and 2016-05176 to T.H. and M.O.), Formas (grant no. 2019-00869 to T.H. and M.O.), and the Novo Nordisk Foundation (grant nos. NNF20OC0063971 and NNF21OC0070309 to T.H. and M.O.). ABIS study (J.L.) was supported by Barndiabetesfonden (Swedish Child Diabetes Foundation); the Swedish Council for Working Life and Social Research, grant/award numbers: FAS2004-1775 and FAS2004-1775; the Swedish Research Council, grant/award numbers: K2005-72X-11242-11A, K2008-69X-20826-01-4, and K2008-69X-20826-01-4; Östgöta Brandstodsbolag; the Medical Research Council of Southeast Sweden (FORSS); the Wallenberg Foundation, grant/award number: K 98-99D-12813-01A; ALF-and LFoU grants from Region Östergötland and Linköping university, Sweden; and Joanna Cocozza Foundation.

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 3 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 = 74270). 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. (J Pediatr 2024;270:114027) ., Funding Agencies|Norwegian Ministry of Health and Care Services; Ministry of Education and Research

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., Funding Agencies|Canadian Institutes of Health Research [OCO-79897, MOP-89886, MSH-95353, ROG-110537]

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. similar to 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., Funding Agencies|Linkoeping University

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., Funding Agencies|Barndiabetesfonden (The Swedish Child Diabetes Foundation); Region Ostergoetlands Stiftelsefonder [RO-760091]

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, Funding Agencies|Juvenile Diabetes Research Foundation