Birth Weight, Childhood and Young Adult Overweight, and the Risk of Coronary Heart Disease in Men.

BACKGROUND: Low birth weight is a known risk factor for adult coronary heart disease (CHD), but the additional effect of weight development during childhood and early adult life has not been studied. METHODS: We included 35 659 men born 1945 to 1961 from the population-based BMI Epidemiology Study Gothenburg, with data available on birthweight, BMI in childhood (8 years), and BMI in young adulthood (20 years). Information on CHD diagnoses was retrieved from national registers. We used Cox proportional hazards regression to estimate hazard ratios and 95% CIs for the risk of early and late CHD (before and after 58.4 years of age, respectively). RESULTS: During follow-up, a total of 3380 cases of CHD (fatal and nonfatal) were registered. Birth weight was inversely associated with the risk of both early (hazard ratio, 0.88 per SD increase [95% CI, 0.84-0.92]) and late (hazard ratio, 0.94 per SD increase [95% CI, 0.90-0.98]) CHD, independently of BMI at 8 years and BMI change during puberty. In a model including birth weight (below or above the median) together with overweight at 8 and 20 years, only birth weight and young adult overweight, but not overweight in childhood, were significantly associated with the risk of CHD. A birth weight below the median, followed by overweight at 20 years of age was associated with a more than doubled risk of early CHD (hazard ratio, 2.29 [95% CI, 1.86-2.81]), compared with the reference (birth weight above the median and normal weight at 20 years of age). This excess risk was even more pronounced for a birthweight below 2.5 kg. CONCLUSIONS: We demonstrate that low birth weight and young adult overweight are important developmental markers of risk for adult CHD. These findings motivate a life course perspective for prevention and risk assessment of adult CHD.

Low birthweight and overweight during childhood and young adulthood and the risk of type 2 diabetes in men: a population-based cohort study.

AIMS/HYPOTHESIS: This study aimed to determine the relative contributions of low birthweight and overweight during childhood and young adulthood to the risk of type 2 diabetes in men. METHODS: We included 34,231 men born between1945 and 1961 from the population-based BMI Epidemiology Study (BEST) Gothenburg with data on birthweight and overweight status in childhood (8 years, BMI >17.9 kg/m2) and young adulthood (20 years, BMI >25 kg/m2). Participants were followed from age 30 years until 31 December 2019. Information on type 2 diabetes diagnoses was retrieved from Swedish national registers. HRs and 95% CIs for the risk of early (≤59.4 years) and late (>59.4 years) type 2 diabetes were estimated using Cox proportional hazards regression. RESULTS: During follow-up, a total of 2733 cases of type 2 diabetes were diagnosed. Birthweight below the median (<3.6 kg) and overweight at age 20 (BMI >25 kg/m2), but not overweight at age 8 (BMI >17.9 kg/m2), were associated with an increased risk of early and late type 2 diabetes. Of note, a birthweight below the median followed by overweight at age 20 years was associated with a substantially increased risk of early type 2 diabetes (HR 6.07, 95% CI 5.08, 7.27), and a low birthweight (≤2.5 kg) combined with overweight at age 20 years was associated with a massive risk of early type 2 diabetes (HR 9.94, 95% CI 6.57, 15.05). CONCLUSIONS/INTERPRETATION: Low birthweight and overweight in young adulthood are the major developmental determinants of adult type 2 diabetes risk in men. They contribute in an additive manner to the risk of type 2 diabetes. To reduce the risk of type 2 diabetes, young adult overweight should be avoided, especially in boys with a low birthweight. DATA AVAILABILITY: The SPSS analysis code, the R analysis code and a data dictionary have been made available in an online repository ( https://osf.io/bx2as/ ).

A low proportion of undertriage validates the new West coast system for triage-Paediatric.

AIM: There is a lack of studies on paediatric triage systems. This study aimed to evaluate patient safety of the Gothenburg-developed paediatric triage system West Coast System for Triage-Paediatric (WEST-P). METHOD: This study was performed at the paediatric emergency department in Gothenburg, Sweden, October 2020 to April 2021. Included patients were double-triaged with the WEST-P, and the established Rapid Emergency Triage and Treatment System-Paediatrics (RETTS-p). We compared the level of urgency between both systems to identify potentially undertriaged patients. Also, we assessed the patient safety according to clinical assessment at presentation, and pre-defined criteria. RESULTS: This study included 2290 (23%) of triaged patients (44% girls, median age: 5.0 years) during the study period. A higher number of patients triaged to low urgency in WEST-P compared to RETTS-p (p < 0.0001) was observed, and 497 cases with low WEST-P and high RETTS-p urgencies identified. Of these, 29 had a clinical assessment indicating high urgency. After patient safety assessment, seven (0.4%) were determined undertriaged by the new triage system WEST-P. CONCLUSION: Our findings demonstrate a low risk of undertriage in the new WEST-P. Thus, the WEST-P has a high degree of patient safety when used in a paediatric emergency department.

Overweight in childhood and young adulthood increases the risk for adult thromboembolic events.

BACKGROUND: Approximately one third of thromboembolic (TE) events are related to obesity, but to which extent elevated body mass index (BMI) during the distinct periods of childhood and puberty contributes is not known. We aimed to evaluate the impact of high BMI during childhood and puberty for the risk of adult venous and arterial thromboembolic events (VTE, ATE, respectively) in men. METHODS: We included 37,672 men from the BMI Epidemiology Study (BEST) Gothenburg with data on weight and height in childhood, young adult age, and on pubertal BMI change. Information on outcomes (VTE [n = 1683], ATE [n = 144], or any first TE event [VTE or ATE; n = 1780]) was retrieved from Swedish national registers. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated by Cox regressions. RESULTS: Both BMI at 8 years of age and the pubertal BMI change were associated with VTE, independently of each other (BMI at 8: HR 1.06 per standard deviation [SD] increase, 95% CI, 1.01;1.11; pubertal BMI change: HR 1.11 per SD increase, 95% CI, 1.06;1.16). Individuals with normal weight during childhood followed by young adult overweight (HR 1.40, 95% CI, 1.15;1.72), and individuals with overweight at both childhood and young adult age (HR 1.48, 95% CI, 1.14;1.92), had a significantly increased risk of VTE in adult life, compared with the normal weight reference group. Individuals with overweight in childhood and in young adult age had increased risk of ATE and TE. CONCLUSION: Young adult overweight was a strong determinant, and childhood overweight a moderate determinant, of the risk of VTE in adult men.

Impact of BMI and smoking in adolescence and at the start of pregnancy on birth weight.

BACKGROUND: Birth weight is an indicator of intra-uterine conditions but also a determinant for future health. The importance of preconception health for a healthy birth weight has been emphasized, but evidence is lacking on how modifiable factors in adolescence, such as body mass index (BMI) and smoking, affect future pregnancy outcome. We evaluated associations between BMI and smoking in adolescence and at the start of pregnancy and birth weight of the first-born child. METHODS: This longitudinal study included 1256 mothers, born 1962-1992, and their first-born children, born between 1982-2016. Self-reported questionnaire information on weight, height and smoking at age 19 was cross-linked with national register data obtained at the start of pregnancy and with the birth weights of the children. Univariable and multivariable linear regressions were performed to determine the impact of maternal factors at 19 years of age and at the start of the pregnancy respectively, and the importance of BMI status at these points of time for the birth weight of the first child. RESULTS: BMI and smoking at the start of the pregnancy displayed strong associations with birth weight in a multivariable analysis, BMI with a positive association of 14.9 g per BMI unit (95% CI 6.0; 23.8 p = 0.001) and smoking with a negative association of 180.5 g (95% CI -275.7; -85.4) p = 0.0002). Smoking and BMI at 19 years of age did not show this association. Maternal birth weight showed significant associations in models at both time-points. Becoming overweight between age 19 and the start of the pregnancy was associated with a significantly higher birth weight (144.6 (95% CI 70.7;218.5) p = 0.0002) compared to mothers with normal weight at both time points. CONCLUSIONS: Our findings indicate that the time period between adolescence and first pregnancy could be a window of opportunity for targeted health promotion to prevent intergenerational transmission of obesity.

Paediatric clinical trials need paediatric clinical trial budgets.

AIM: Clinical trials and the need for new treatments were recently listed among the most important factors for child health. The aim of the present study was to describe some of our experiences with budget preparations in paediatric clinical trials. METHODS: We selected 10 trials sponsored by the pharmaceutical industry at the Pediatric Clinical Research Center at Sahlgrenska University Hospital in Gothenburg, Sweden. We compared the sponsor's initial budget (budget proposal from the sponsor), with the final budget (negotiated and agreed between sponsor and site) and identified areas where discrepancies may arise. RESULTS: The mean difference in total budget amount between the initial budget and the final budget was +60% (mean 59%, range 31%-139%). The costs for preparation of the clinical trial, time spent for study activities and costs for examinations were identified as key budget items for these differences. CONCLUSION: Our findings indicate that a substantial part of the trial-related costs would not be covered by the sponsor, had the initial budget been accepted. A thorough review and budget negotiation, as well as to have a dedicated team member for this task, are essential to ensure equitable responsibility for the study-related costs and to avoid discontinuation of trials.

A secular trend of increasing pubertal BMI change among Swedish adolescents.

Pubertal BMI change is an independent risk marker of cardiovascular mortality/morbidity. Previous studies demonstrated a secular trend of increased childhood BMI but it is unknown if there is a concomitant secular trend regarding pubertal BMI change. The aim of this study was to describe the trend in pubertal BMI change. We collected heights and weights before and after puberty from school health records and military conscript records for boys born every five years during 1946-1991 (n = 3650, total cohort) and calculated pubertal BMI change (young adult BMI at 20 years of age minus childhood BMI at 8 years of age) for all study participants. A secular trend of increasing pubertal BMI change during the study period was observed. The increase in pubertal BMI change (0.27 kg/m2 per decade [0.22; 0.32]) explained 54% of the secular trend of increasing young adult BMI (0.50 kg/m2 per decade [0.43; 0.57]). We made the novel observation that there is a secular trend of increasing pubertal BMI change. We propose that the secular trend of increasing pubertal BMI change might contribute more than the secular trend of increasing childhood BMI to the adverse cardiovascular health consequences associated with the ongoing obesity epidemic.

Health technology assessment of paediatric medicines: European landscape, challenges and opportunities inside the conect4children project.

The medicine development process is complex and requires time and effort to ensure safety, efficacy and quality. In paediatrics, this process is even more challenging, as it involves a subgroup of the population that already faces a considerable gap in the clinical evaluation of medicines and devices compared to the adult population. Moreover, access to therapies is heavily influenced by national health technology assessment (HTA) recommendations, which often form the basis for pricing and reimbursement decisions that affect the availability of effective treatments within the national health systems. Yet performing an HTA to assess the relative effectiveness and cost-effectiveness of a new children's treatment has several non-trivial implications, creating a critical issue for the paediatric population. In addition, the advent of innovative health technologies for children emphasises the need to empower the role of HTAs in paediatrics. This article aims at describing the most relevant elements of the drug development process in the paediatric field by focusing on the HTA. Particular attention will be paid to the factors that influence market access for new paediatric medicines and patients' access to treatment. The article will also highlight some central methodological challenges in conducting HTA in the paediatric field. Finally, the article will provide insight into how initiatives, such as conect4children, may subsequently reinforce HTA awareness in the paediatric community and strengthen collaborations through network mechanisms.

c4c: Paediatric pharmacovigilance: Methodological considerations in research and development of medicines for children - A c4c expert group white paper.

Children frequently respond differently to therapies compared to adults. Differences also exist between paediatric age groups for pharmacokinetics and pharmacodynamics in both efficacy and safety. Paediatric pharmacovigilance requires an understanding of the unique aspects of children with regard to, for example, drug response, growth and development, clinical presentation of adverse drug reactions (ADRs), how they can be detected and population-specific factors (e.g., more frequent use of off-label/unlicensed drugs). In recognition of these challenges, a group of experts has been formed in the context of the conect4children (c4c) project to support paediatric drug development. This expert group collaborated to develop methodological considerations for paediatric drug safety and pharmacovigilance throughout the life-cycle of medicinal products which are described in this article. These considerations include practical points to consider for the development of the paediatric section of the risk management plan (RMP), safety in paediatric protocol development, safety data collection and analysis. Furthermore, they describe the specific details of post-marketing pharmacovigilance in children using, for example, spontaneous reports, electronic health care records, registries and record-linkage, as well as the use of paediatric pharmacoepidemiology studies for risk characterisation. Next the details of the assessment of benefit-risk and challenges related to medicinal product formulation in the context of a Paediatric Investigation Plan (PIP) are presented. Finally, practical issues in paediatric signal detection and evaluation are included. This paper provides practical points to consider for paediatric pharmacovigilance throughout the life-cycle of medicinal products for RMPs, protocol development, safety data collection and analysis and PIPs.

Current knowledge, challenges and innovations in developmental pharmacology: A combined conect4children Expert Group and European Society for Developmental, Perinatal and Paediatric Pharmacology White Paper.

Developmental pharmacology describes the impact of maturation on drug disposition (pharmacokinetics, PK) and drug effects (pharmacodynamics, PD) throughout the paediatric age range. This paper, written by a multidisciplinary group of experts, summarizes current knowledge, and provides suggestions to pharmaceutical companies, regulatory agencies and academicians on how to incorporate the latest knowledge regarding developmental pharmacology and innovative techniques into neonatal and paediatric drug development. Biological aspects of drug absorption, distribution, metabolism and excretion throughout development are summarized. Although this area made enormous progress during the last two decades, remaining knowledge gaps were identified. Minimal risk and burden designs allow for optimally informative but minimally invasive PK sampling, while concomitant profiling of drug metabolites may provide additional insight in the unique PK behaviour in children. Furthermore, developmental PD needs to be considered during drug development, which is illustrated by disease- and/or target organ-specific examples. Identifying and testing PD targets and effects in special populations, and application of age- and/or population-specific assessment tools are discussed. Drug development plans also need to incorporate innovative techniques such as preclinical models to study therapeutic strategies, and shift from sequential enrolment of subgroups, to more rational designs. To stimulate appropriate research plans, illustrations of specific PK/PD-related as well as drug safety-related challenges during drug development are provided. The suggestions made in this joint paper of the Innovative Medicines Initiative conect4children Expert group on Developmental Pharmacology and the European Society for Developmental, Perinatal and Paediatric Pharmacology, should facilitate all those involved in drug development.

Pubertal Body Mass Index Change Is Associated With Adult Coronary Atherosclerosis and Acute Coronary Events in Men.

OBJECTIVE: The aim with the present study was to evaluate the association between pubertal body mass index (BMI) change and adult coronary artery calcification (CAC) score and risk of acute coronary events. APPROACH AND RESULTS: We included 37 672 men from the BMI Epidemiology Study and calculated their pubertal BMI change (BMI at 20 years−BMI at 8 years). Coronary artery computed tomography analysis of CAC score, midlife BMI, and major risk factors for coronary heart disease were available for a sub-cohort through linkage with the SCAPIS (Swedish Cardio Pulmonary Bioimage Study) cohort (n=922). Information on first acute coronary events was retrieved from Swedish national registers (n=37 672, events n=1873). Pubertal BMI change (odds ratio per SD increase, 1.32 [1.14­1.52]), but not childhood BMI, was associated with middle age CAC score ≥1. This association for pubertal BMI change was maintained after adjustment for midlife BMI at CAC analysis and in a model including major cardiovascular risk factors. Individuals who became overweight during puberty (hazard ratio, 2.11 [1.79­2.49]), but not those overweight at 8 years who normalized their weight during puberty, had substantially increased risk of acute coronary events compared with men who were never overweight. Among subjects with an acute coronary event, individuals with pubertal onset overweight were at increased risk of death due to the event. CONCLUSIONS: Pubertal BMI change is an independent predictor of CAC score and risk of acute coronary events in adult men. Excessive BMI increase during puberty may initiate the coronary atherosclerotic process, thereby increasing the risk and severity of adult acute coronary events.

Celiac disease screening at a pediatric outpatient clinic: a feasibility study.

OBJECTIVES: Celiac disease (CD) is a common yet largely underdiagnosed disease. This study aimed to test the feasibility of incorporating a non-targeted CD screening in a pediatric outpatient setting and evaluate its short-term impact on children with serological evidence of disease. METHODS: Over five months, 500 children (aged 2-17 years) attending a general pediatric outpatient clinic in Gothenburg, Sweden, were enrolled and surveyed for current symptoms, quality of life, and background characteristics; 481 children were screened for tissue-transglutaminase antibodies (tTGA); repeated tTGA-positivity was defined as CD autoimmunity (CDA). Children with CDA were investigated for CD and for one year monitored for changes in symptoms, and quality of life. RESULTS: Eleven of 481 (2.3%) screened children had CDA. Children with CDA were younger (median 3.8 years) than those without CDA (8.8 years). No other major between-group differences were reported in background characteristics, symptoms, or quality of life. The screening was well-accepted by the families/participants. During 1-year follow-up, 8 of 11 children with CDA were diagnosed with CD. Children with screening-detected CD reported no significant changes in symptoms and quality of life and the dietary adherence rate was good. CONCLUSIONS: Non-targeted screening for CD was feasible in a general pediatric outpatient setting. While hampered by small sample size, our results are in line with previous screening studies indicating that symptoms do not differentiate CDA from non-CDA children. Also, among an overall minimal-symptomatic group of children, diagnosing CD and installation of treatment did not significantly change their well-being during 1-year follow-up.

Low Birth Weight as an Early-Life Risk Factor for Adult Stroke Among Men.

OBJECTIVE: To evaluate the association between birth weight and the risk of adult stroke in men, independent of body mass index (BMI) at young adult age. STUDY DESIGN: We included 35 659 men born between 1945 and 1961 from the BMI Epidemiology Study with data on birth weight together with BMI in childhood (8 years) and young adulthood (20 years). Information on stroke events (1184 first stroke events; 905 ischemic stroke [IS] events and 234 intracerebral hemorrhage [ICH] events) was retrieved from national registers in Sweden. RESULTS: Birth weight was inversely associated with the risk of stroke (IS, ICH and uncategorized together; hazard ratio [HR], 0.88 per SD increase, 95% CI, 0.84-0.93), IS, and ICH in a linear manner, independent of young adult BMI. This association was maintained when the analysis was restricted to individuals within the normal birth weight range only. Moreover, individuals with a birth weight in the lowest tertile followed by overweight at 20 years had an 81% greater risk of stroke (HR, 1.81; 95% CI, 1.29; 2.54), compared with a reference group of individuals with birth weight in the middle tertile who were of normal weight at age 20 years. CONCLUSIONS: We demonstrate an inverse association between birth weight and the risk of adult stroke, IS, and ICH independent of young adult BMI. These findings suggest that low birth weight should be included in assessments of stroke risk in adults.

Prevalence of overweight and obesity from 5 to 19 years of age in Gothenburg, Sweden.

AIM: The aim of this study was to present prevalence data for overweight and obesity across school age in a large, recent, population-based cohort of children in Gothenburg, Sweden. METHODS: We included 66,807 children (48.5% girls) aged 5-18.9 years who had their height and weight measured in school health care 2015-2018. The BMI values were categorised according to the age-dependent cut-offs for overweight and obesity from the International Obesity Task Force (IOTF). RESULTS: Overall, the prevalence of overweight and obesity for girls and boys was 18.1% and 18.0%, respectively. We observed increasing proportions of overweight (girls 11.5-17.1% and boys 8.4-17.4%) and obesity (girls 3.0-4.2% and boys 2.7-6.1%) with increasing age (p < 0.001 for trend in both sexes). Moreover, girls had higher prevalence of overweight during ages 5.0 to 8.9 years compared with boys (p < 0.001), while boys had higher prevalence of obesity 15.0-18.9 years compared with girls (p < 0.001). CONCLUSION: In conclusion, we demonstrate increasing prevalence of overweight and obesity across the entire school age range, as well as differences in prevalences between boys and girls, in a population-based sample of 67,000 children in Gothenburg city, Sweden. Continuous monitoring of schoolchildren, together with effective preventive measures, is crucial to curb the obesity epidemic and its consequences.

Early puberty and risk for type 2 diabetes in men.

AIMS/HYPOTHESIS: The association between pubertal timing and type 2 diabetes, independent of prepubertal BMI, is not fully understood. The aim of the present study was to evaluate the association between pubertal timing and risk of adult type 2 diabetes, independent of prepubertal BMI, in Swedish men. METHODS: We included 30,697 men who had data for BMI at age 8 and 20 years and age at Peak Height Velocity (PHV), an objective assessment of pubertal timing, available from the BMI Epidemiology Study Gothenburg (BEST Gothenburg), Sweden. Information on type 2 diabetes (n = 1851) was retrieved from the Swedish National Patient Register. HRs and 95% CIs were estimated by Cox regression analysis. We observed violations of the assumption of proportional hazards for the association between age at PHV and the risk of type 2 diabetes and therefore split the follow-up period at the median age of type 2 diabetes diagnosis (57.2 years of age) to define early (≤57.2 years) and late (>57.2 years) type 2 diabetes diagnosis. RESULTS: Age at PHV was inversely associated with both early (HR 1.28 per year decrease in age at PHV, 95% CI 1.21, 1.36) and late (HR 1.13, 95% CI 1.06, 1.19) type 2 diabetes. After adjustment for childhood BMI, the associations between age at PHV and both early (HR 1.24, 95% CI 1.17, 1.31) and late (HR 1.11, 95% CI 1.05, 1.17) type 2 diabetes were similar. Moreover, early age at PHV predicted insulin treatment of type 2 diabetes (OR 1.25 per year decrease in age at PHV, 95% CI 1.17, 1.33). Assuming a higher risk among those with an age at PHV below the median, the population attributable factor indicates that 15% fewer of the diagnosed individuals would have developed type 2 diabetes had they not reached puberty early. CONCLUSIONS/INTERPRETATION: These findings indicate that early puberty may be a novel independent risk factor for type 2 diabetes.

Childhood body mass index is associated with the risk of adult hematologic malignancies in men-The best Gothenburg cohort.

Hematologic malignancies are common and the incidence is increasing. Adult obesity has been associated with hematologic malignancies (HM), but the importance of body mass index (BMI) in childhood and during puberty has not been evaluated. The aim of the present study was to evaluate the relative contribution of BMI and height in childhood and during puberty for the risk of adult HM. 37 669 men born in 1946 to 1961 who had weight and height measured at 8 (childhood) and 20 (young adult age) years of age available from the BMI Epidemiology Study were included in the study. Pubertal BMI change was calculated as BMI at 20 years of age minus BMI at 8 years of age. Information on HM was retrieved from Swedish registers (459 cases of HM). Hazard ratios (HR) and 95% confidence intervals (CI) were estimated by Cox regressions. Childhood BMI (HR 1.11 per SD increase [95% CI 1.02-1.23]), but not pubertal BMI change, was associated with hematologic malignancies in a linear manner. Childhood BMI was, independent of childhood height, associated with the diagnostic entities Non-Hodgkin lymphoma (HR 1.14 [95% CI 1.00-1.30]) and its largest subgroup diffuse large B-cell lymphoma (HR 1.31 [95% CI 1.03-1.67]). Childhood height was associated with multiple myeloma (HR 1.30 [95% CI 1.04-1.64]) independent of childhood BMI. We conclude that childhood but not puberty is the critical developmental period regarding future risk of HM and we suggest that elevated childhood BMI is a determinant of Non-Hodgkin lymphoma and diffuse large B-cell lymphoma.

Pubertal BMI change and adult-onset asthma in men: Population-based cohort study in Sweden.

BACKGROUND: The role of pubertal BMI change in adult-onset concomitant asthma and allergic rhinitis is unknown. OBJECTIVE: We investigated the association of childhood and young adult BMI, and pubertal BMI changes with adult-onset asthma, allergic rhinitis, and concomitant asthma and rhinitis in Swedish men. METHODS: The BMI Epidemiology Study in Gothenburg, Sweden, comprised of height and weight measures taken from school health records (6.5-9.5 years) and during military conscription (17.5-22 years) for all men born 1945-1961 (n = 37 652). Age-adjusted childhood BMI centred at 8 years and young adult BMI at 20 years were linked to high quality data on asthma and allergic rhinitis diagnoses from the Swedish National Patient Register. FINDINGS: High BMI (4th quartile vs the two median quartiles) at 8 years was associated with increased risk of concomitant asthma and allergic rhinitis (HR 1.45; 95% CI 1.00-2.11). Overweight (HR 1.45; 95% CI 1.12-1.89) and obesity (HR 1.95; 95% CI 1.08-3.54) at 20 years were associated with increased risk of asthma without concomitant allergic rhinitis as main or auxiliary diagnosis. Pubertal BMI change showed a non-linear association, so that both low (1st quartile vs the two median quartiles) and high pubertal BMI changes were associated with increased risk of asthma (low: HR 1.36; 95% CI 1.11-1.68; high: HR 1.32; 95% CI 1.07-1.63) and asthma without concomitant allergic rhinitis (low: HR 1.33; 95% CI 1.04-1.69; high: HR 1.36; 95% CI 1.07-1.74) as a main diagnosis. CONCLUSIONS AND CLINICAL RELEVANCE: Both low and high pubertal BMI changes are predictors of adult-onset asthma in men, particularly asthma without concomitant allergic rhinitis. Primary prevention of adult-onset asthma requires monitoring of changes in BMI during puberty.

Growth and Pubertal Timing in Boys With Adult-diagnosed Celiac Disease: A Population-based Longitudinal Cohort Study.

There are few longitudinal data on whether childhood growth and pubertal timing may be impaired by adult-diagnosed celiac disease (CD). Through school health care records and national registers, we retrieved serial growth measurements on 37,672 Swedish boys born in 1945 to 1961, out of whom 72 (0.2%) were clinically diagnosed with CD as adults. Boys with, versus without, adult-diagnosed CD exhibited no appreciable mean differences in body mass index (BMI, kg/m) and height (cm) at ages 8 or 20 to 21 years (childhood BMI, 15.9 [CD] vs 15.7 [comparators]; childhood height, 129.1 [CD] vs 128.6 [comparators]; adult BMI, 21.3 [CD] vs 21.4 [comparators]; adult height, 180.7 [CD] vs 180.4 [comparators]). Neither did we observe any between-group differences in growth development during puberty nor in the timing of pubertal growth spurt (all P values ≥0.30). Conclusively, in this population-based longitudinal study, boys with adult-diagnosed CD had similar growth and pubertal timing as their peers.

The Convention on the Rights of the Child (UNCRC) and its implementation in paediatric clinical research.

The amount of research being performed in children, in particular pharmacological research, is lower than in adults, which is in direct contrast to the aims of the UN Convention on the Rights of the Child. A Pediatric Clinical Research Center (PCRC) has been established at Sahlgrenska University Hospital with the aim of supporting clinical research in children and adolescents. The number of inquiries and initiated clinical studies at PCRC has increased since the start in 2016. In addition, there is a need for regional and national infrastructures for paediatric clinical research and a national network for paediatric clinical studies. CONCLUSION: Sahlgrenska University Hospital has established an infrastructure to support paediatric research and to work with national networks and infrastructures.

Improved infrastructure and support needed for paediatric clinical trials in Sweden.

AIM: There is a lack of authorised medicines for paediatric patients and improved drug development is necessary. The aim of this study was to evaluate the need for infrastructure and support for paediatric clinical trials in Sweden. METHODS: A web-based survey was sent to doctors and nurses involved in the care of neonates, children and adolescents assessing the current situation and future needs for paediatric clinical trials in Sweden. Questions regarding premises, competence, organisation, support for paediatric clinical trials and Good Clinical Practice Training were addressed. RESULTS: In total, 137 individuals responded to the survey (109 doctors and 28 nurses). Overall, 61% of the respondents had previous experience of paediatric clinical trials. Some respondents had access to trial units, but only 34% had used the trial unit for support. Half of the responders were interested in recurrent paediatric Good Clinical Practice training. Doctors responded that clinical work often had to be prioritised and emphasised the need for research time. CONCLUSION: This study clearly shows the commitment for clinical trials among doctors and nurses involved in paediatric care in Sweden, but also that administrative, logistic and economic support in a sustainable setting and an expanded national collaboration are needed.