Heart disease in pregnancy and risk of pre-eclampsia: a Swedish register-based study.

BACKGROUND AND AIMS: Pre-eclampsia complicates 3-5% of pregnancies worldwide and is associated with adverse outcomes for the mother and the offspring. Pre-eclampsia and heart failure have common risk factors, including hypertension, obesity and diabetes. It is not known whether heart failure increases the risk of pre-eclampsia. This study examines whether pregestational heart failure increases the risk of pre-eclampsia. METHODS: In a registry-based case-cohort study that included all pregnancies in Sweden (n=3 125 527) between 1990 and 2019, all pregnancies with pre-eclampsia (n=90 354) were identified and up to five control pregnancies (n=451 466) for each case were chosen, matched on the mother's birth year. Multiple logistic regression analysis was used to evaluate the impact of heart failure on the risk of pre-eclampsia, with adjustment for established risk factors and other cardiovascular diseases. RESULTS: Women with heart failure had no increased risk for pre-eclampsia, OR 1.02 (95% CI 0.69 to 1.50). Women with valvular heart disease had an increased OR of preterm pre-eclampsia, with an adjusted OR of 1.78 (95% CI 1.04 to 3.06). Hypertension and diabetes were independent risk factors for pre-eclampsia. Obesity, multifetal pregnancies, in vitro fertilisation, older age, Nordic origin and nulliparity were more common among women who developed pre-eclampsia compared with controls. CONCLUSION: Women with heart failure do not have an increased risk of pre-eclampsia. However, women with valvular heart disease prior to pregnancy have an increased risk of developing preterm pre-eclampsia independent of other known risk factors.

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.

Melatonin Prescription in Children and Adolescents in Relation to Body Weight and Age.

The prescription of melatonin to children and adolescents has increased dramatically in Sweden and internationally during the last ten years. In the present study we aimed to evaluate the prescribed melatonin dose in relation to body weight and age in children. The population-based BMI Epidemiology Study Gothenburg cohort has weight available from school health care records, and information on melatonin prescription through linkage with high-quality national registers. We included prescriptions of melatonin to individuals below 18 years of age where a weight measurement not earlier than three months before, or later than six months after the dispensing date, was available (n = 1554). Similar maximum doses were prescribed to individuals with overweight orobesity as to individuals with normal weight, and to individuals below and above 9 years of age. Age and weight only explained a marginal part of the variance in maximum dose, but were inversely associated and explained a substantial part of the variance in maximum dose per kg. As a result, individuals overweight or with obesity, or age above 9 years, received lower maximum dose per kg of body weight, compared with individuals with normal weight or below 9 years of age. Thus, the prescribed melatonin dose to individuals under 18 years of age is not primarily informed by body weight or age, resulting in substantial differences in prescribed dose per kg of body weight across BMI and age distribution.

Birth weight and young adult body mass index for predicting the risk of developing adult heart failure in men.

AIMS: Hospitalizations for heart failure among young adults and middle-aged individuals have increased. The aims of the present study were to evaluate the association between birth weight and risk of adult heart failure and the importance of change from low birth weight to overweight/obesity at young adulthood. METHODS AND RESULTS: We used the population-based body mass index (BMI) Epidemiology Study cohort Gothenburg (n = 35 659) with birth weight and young adult BMI (20 years) available from child healthcare records, school health records, and military conscription register for men born 1945-1961. The cohort includes all children who finished school, which was mandatory, in Gothenburg, Sweden. Information on heart failure diagnosis was retrieved from the National Patient Register and the Cause of Death Register (n = 415). In cox regression analyses, there was an inverse association between birth weight and risk of heart failure [hazard ratio (HR) 0.83 per standard deviation (SD), 95% confidence interval (CI) 0.76-0.90], and a direct association for young adult BMI (HR 1.48 per SD, 95% CI 1.36-1.61). Of note, individuals with birth weight in the lowest tertile, who were overweight/obese in young adulthood had a five-fold risk of heart failure (HR 4.95, 95% CI 3.36-7.31) compared with individuals in the middle birth weight tertile who were normal weight at 20 years. CONCLUSIONS: Birth weight was inversely associated with the risk of hospitalization due to heart failure. The combination of low birth weight and overweight/obesity in young adulthood results in excess risk of heart failure beyond that of low birth weight or young adult overweight/obesity separately. These findings indicate the need of a life course perspective in heart failure prevention and risk assessment.

Timing of the Pubertal Growth Spurt and Prostate Cancer.

Previous studies of pubertal timing and the risk of prostate cancer have used self-reported markers of pubertal development, recalled in mid-life, and the results have been inconclusive. Our aim was to evaluate the age at the pubertal growth spurt, an objective marker of pubertal timing, and the risk of prostate cancer and high-risk prostate cancer. This population-based cohort study included 31,971 men with sufficient height measurements to calculate age at peak height velocity (PHV). Outcomes were accessed through national registers. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated by Cox regressions with follow up starting at 20 years of age. In total, 1759 cases of prostate cancer including 449 high-risk were diagnosed during follow up. Mean follow up was 42 years (standard deviation 10.0). Compared to quintiles 2-4 (Q2-4), men in the highest age at PHV quintile (Q5) had lower risk of prostate cancer (HR 0.83, 95% CI 0.73-0.94), and of high-risk prostate cancer (0.73; 0.56-0.94). In an exploratory analysis with follow up starting at age at PHV, late pubertal timing was no longer associated with reduced risk of prostate cancer. Later pubertal timing was associated with reduced risk of prostate cancer and especially high-risk prostate cancer. We propose that the risk of prostate cancer might be influenced by the number of years with exposure to adult levels of sex steroids.

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.

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.

Secular Trends in Pubertal Growth Acceleration in Swedish Boys Born From 1947 to 1996.

IMPORTANCE: A secular trend for earlier menarcheal age has been established in girls but there are few studies of pubertal timing for boys. OBJECTIVE: To determine if there is a secular trend for earlier pubertal timing among boys. DESIGN, SETTING, AND PARTICIPANTS: For this population-based retrospective cohort study conducted in Gothenburg, Sweden, we collected heights and weights from school health records for boys born consecutively from January 1 and onwards in 1947 and every 5 years from 1951 to 1996 (n = 375 for each birth cohort from 1947-1991, n = 340 for the birth cohort in 1996, and n = 4090 for the total cohort). We estimated age at the peak height velocity (PHV), the maximum growth velocity during puberty, and childhood body mass index (BMI) at age 8 years for all study participants. The data were analyzed during 2018 and 2019. Boys were eligible if they had a complete personal identity number and data to calculate their age at PHV and childhood BMI. Approximately 2.4% of the original study population was excluded because they lacked a personal identity number, and in the remaining study population, 4090 (69%) had sufficient data to calculate childhood BMI and age at PHV. EXPOSURES: The exposure was birth year and a potential confounding factor was childhood BMI. MAIN OUTCOMES AND MEASURES: The outcome was age at PHV. RESULTS: Of the 4090 participants, most were white and the mean (SD) age at PHV was 13.9 (1.1) years. A linear regression model revealed a significant association between year of birth and age at PHV. Age at PHV was 1.5 months earlier for every decade increase in birth year (95% CI, -1.72 to -1.19; P < .001). After adjusting for childhood BMI, age at PHV was 1.2 months earlier per decade increase in birth year (95% CI, -1.41 to -0.89). All analyses were repeated in the subgroup of boys born in Sweden and with parents born in Sweden with similar results, indicating that the secular trend was not explained by demographic changes in the population between 1947 and 1996. CONCLUSIONS AND RELEVANCE: We provide evidence of a secular trend for earlier pubertal timing in boys that is partially explained by an increased childhood BMI, but other factors that are unknown contribute.

Childhood Body Mass Index Is Associated with Risk of Adult Colon Cancer in Men: An Association Modulated by Pubertal Change in Body Mass Index.

BACKGROUND: The relative contribution of childhood and pubertal body mass index (BMI) for the risk of adult colorectal cancer is not known. The aim of this study was to evaluate the independent associations for childhood BMI and pubertal BMI change with risk of colorectal cancer in men. METHODS: We included 37,663 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. Information on colorectal cancer was retrieved from the Swedish National Patient Register (257 cases of colon cancer and 159 cases of rectal cancer). RESULTS: Childhood BMI at 8 years of age [HR, 1.19 per SD increase; 95% confidence interval (CI), 1.06-1.33], but not pubertal BMI change (HR, 1.02; 95% CI, 0.90-1.15), was associated with increased risk of colon cancer. Due to a significant interaction between childhood BMI and pubertal BMI change (P < 0.001), we stratified the analyses according to the median of pubertal BMI change. Childhood BMI was associated with risk of colon cancer in individuals with a pubertal BMI change above, but not below, the median (above: HR = 1.48, 95% CI, 1.26-1.74; below: HR = 0.95, 95% CI, 0.80-1.12). Neither childhood BMI nor pubertal BMI change was associated with rectal cancer. CONCLUSIONS: High childhood BMI was associated with increased risk of colon cancer only if it was followed by a pubertal BMI increase above the median. IMPACT: Further studies should evaluate prepubertal childhood BMI in relation to pubertal BMI change and BMI in middle age for the risk of colon cancer.

Secular trends of birthweight in boys from 1950 to 2010.

BACKGROUND: Birthweight is an indicator of fetal development and intrauterine conditions and is associated with future health outcomes. Secular birthweight trends prior to the 1970s are mostly unknown. Our aim was to explore secular birthweight trends in Swedish boys from 1950 to 2010. METHODS: We have collected detailed growth data including birthweight from archived School Health Care records for children born in Gothenburg from 1946 and onwards and established a unique population-based cohort, the Body Mass Index Epidemiology Study (BEST). The birthweight cohort spans six decades (1950-2010) and includes 46,548 boys. RESULTS: The mean birthweight of the complete study cohort was 3580 ± 562 g. Linear regression analysis of the entire period revealed a minimal negative secular trend for birthweight (BETA = -0.4 g/year; p < 0.01). However, three distinct trends appeared during sub-periods: a decrease 1950-80, an increase 1980-2000 and another decrease 2000-2010. CONCLUSION: We demonstrate that birthweight in boys has undergone periodic decreases and subsequent increases, but the overall trend from the 1950s to the present is stable.

Childhood BMI is inversely associated with pubertal timing in normal-weight but not overweight boys.

Background: An inverse association between childhood body mass index (BMI; in kg/m2) and pubertal timing is well established for girls. Among boys, studies are scarce and the results inconclusive. Objective: We aimed to determine the association between childhood BMI and age at peak height velocity (PHV) in boys. Design: We collected height and weight measurements between 6.5 and 22 y of age for boys born 1945-1961 (original cohort; n = 31,971; mean ± SD childhood BMI: 15.74 ± 1.41; age at PHV: 14.06 ± 1.11 y) and 1981-1996 (replication cohort; n = 1465; childhood BMI: 16.47 ± 2.06; age at PHV: 13.71 ± 1.08 y) attending schools in Gothenburg, Sweden, and examined at mandatory military conscription. Age at PHV was obtained from curve-fitting of measured heights with the use of a modified Infancy-Childhood-Puberty model. Results: In the original cohort, childhood BMI was inversely associated with age at PHV (P < 0.001) and a significant quadratic term for childhood BMI (P < 0.001) indicated the nonlinearity of this association. Via piecewise linear regression, we identified a threshold for the association at a childhood BMI of 18.42. A significant inverse association was observed below (ß: -0.17 y/BMI unit; 95% CI: -0.18, -0.16 y/BMI unit) but not above (ß: 0.02 y/BMI unit; 95% CI: -0.03, 0.06 y/BMI unit) this childhood BMI threshold. For every unit increase in childhood BMI, age at PHV was ∼2 mo earlier up to the childhood BMI threshold. Similar results were observed in the replication cohort, demonstrating a significant inverse association below (ß: -0.16; 95% CI: -0.21, -0.11) but not above (ß: -0.03; 95% CI: -0.11, 0.05) the childhood BMI threshold. The identified threshold was close to the cutoffs for overweight at 8 y of age, and childhood BMI was inversely associated with age at PHV below but not above the overweight cutoffs. Conclusions: The present findings establish an inverse association between childhood BMI and pubertal timing in normal-weight but not overweight boys.

Adherence to treatment guidelines for acute otitis media in children. The necessity of an effective strategy of guideline implementation.

OBJECTIVES: Acute otitis media is the single diagnosis responsible for most prescriptions of antibiotics in Sweden and the USA. The treatment of acute otitis media has significant impact on child health, healthcare costs, and the development of anti-microbial resistance. In the Swedish national guidelines from the year 2000, watchful waiting was recommended for most children over 2 years of age. The aims of the present study were to assess the degree of adherence to acute otitis media guidelines at a busy pediatric emergency department of a university hospital and to determine whether an information campaign changed the result. METHODS: Audit of 91 patient records before and 80 patient records after an information campaign consisting of an oral presentation, posting of flow charts, and sending of educational material to prescribing physicians. Four endpoints were studied: choosing to use antibiotics, choice of antibiotic, dosage of antibiotic, and duration of treatment. RESULTS: Before the information campaign, adherence to guidelines was between 70% (dosage) and around 90% (duration). No significant change was seen after the information campaign. The endpoint choosing to use antibiotics showed a large divergence in adherence in children under 2 years (96%) compared to older children (39%). CONCLUSIONS: Overall adherence to recommendations was 70-90% but adherence to watchful waiting was poor. Information did not improve adherence, suggesting insufficient educational power or the existence of barriers other than lack of knowledge. Specific barriers should be identified, and implementation and follow-up should be part of producing guidelines in order to achieve the desired results.