Childhood body mass index and the subsequent risk of anorexia nervosa and bulimia nervosa among women: A large Danish population-based study.

OBJECTIVE: Evidence linking childhood body mass index (BMI) with subsequent eating disorders is equivocal. Potential explanations include different study populations and size, and that anorexia nervosa (AN) and bulimia nervosa (BN) should be studied separately. We examined whether birthweight and childhood BMI were associated with subsequent risk of AN and BN in girls. METHOD: We included 68,793 girls from the Copenhagen School Health Records Register born between 1960 and 1996 with information on birthweight and measured weights and heights obtained from school health examinations at ages 6-15 years. Diagnoses of AN and BN were retrieved from Danish nationwide patient registers. We used Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: We identified 355 cases of AN (median age: 19.0) and 273 cases of BN (median age: 21.8). Higher childhood BMI was linearly associated with decreasing risk of AN and increasing risk of BN at all childhood ages. At age 6, the HR for AN was 0.85 (95% CI: 0.74-0.97) per BMI z-score and the HR for BN was 1.78 (95% CI: 1.50-2.11) per BMI z-score. Birthweight >3.75 kg was associated with increased risk of BN compared to a birthweight of 3.26-3.75 kg. CONCLUSION: Higher BMI in girls at ages 6-15 years was associated with decreasing risk of AN and increasing risk of BN. Premorbid BMI could be relevant for the etiology of AN and BN, and in identifying high risk individuals. PUBLIC SIGNIFICANCE: Eating disorders are associated with elevated mortality, especially AN. Using a cohort of Copenhagen school children, we linked information on BMI at ages 6-15 years for 68,793 girls with nationwide patient registers. Low childhood BMI was associated with increased risk of AN, whereas high childhood BMI was associated with increased risk of BN. These findings may assist clinicians in identifying individuals at high-risk of these diseases.

Early detection of childhood overweight and related complications in a Danish population-based cohort aged 2-8 years.

BACKGROUND: Overweight in early childhood often tracks into adolescence and adulthood and early childhood is a critical period for developing sustained overweight. This study aims to investigate the early detection of childhood overweight (including obesity) and related cardiometabolic complications in a Danish population-based cohort of children aged 2.5-8 years in collaboration with primary care municipal dental clinics and public health nurses. METHODS: In this prospective population-based cohort study, 335 pre-school children (age 2.5 and 5 years) were recruited from municipal dental clinics, and 657 school children (age 6-8 years) by public health nurses. A subgroup of 392 children (40%) participated in additional hospital-based examinations including blood pressure measurement and a blood sample. Children were re-examined approximately one year later. RESULTS: The prevalence of overweight was 13.73% in pre-school children and 13.69% in school children at baseline. In the pre-school children, differences in cardiometabolic risk markers between children with and without overweight were minor, whereas in school children with overweight, cardiometabolic derangements were manifest including significantly higher levels of fasting glucose, insulin, homoeostasis model of assessment for insulin resistance, triglycerides, and alanine aminotransferase and lower levels of high-density lipoprotein cholesterol. During follow-up the prevalence of overweight did not change in pre-school children but increased to 17.0% in school children. CONCLUSIONS: Existing contacts with the primary health care sector, including dental care, can successfully be used for detection of overweight. This study suggests that early detection should be initiated at pre-school ages since overweight-related complications are already established by school ages.

Neonatal Anthropometrics and Obesity Treatment Response in Children and Adolescents.

OBJECTIVE: To investigate the relationship between in utero growth conditions, as indicated by neonatal anthropometric measures, and childhood obesity treatment response, to examine the potential usefulness of neonatal anthropometrics as a potential childhood obesity treatment stratification tool. STUDY DESIGN: The study included 2474 children and adolescents with obesity (mean age, 11.2 years; range, 5.0-18.9 years) treated at the Children's Obesity Clinic in Holbæk, Denmark. Treatment response was registered prospectively, and neonatal data were collected from national electronic registers. RESULTS: Birth weight, birth length, birth weight for gestational age, and large for gestational age status were positively associated with the degree of obesity at treatment initiation. After a mean (SD) of 1.27 (0.69) years of enrollment in obesity treatment, the children exhibited a mean reduction of -0.32 (0.50) in body mass index SD score. No significant associations between neonatal anthropometric measures and childhood obesity treatment response were detected. CONCLUSIONS: Neonatal anthropometric measures were positively associated with the degree of obesity at treatment initiation but not with response to multidisciplinary treatment of childhood obesity. Individualization of obesity treatment based on neonatal anthropometry does not seem warranted.

Early life body size in relation to risk of renal cell carcinoma in adulthood: a Danish observational cohort study.

Adult obesity increases risks of renal cell carcinoma (RCC). This study investigated if birth weight, child body mass index (BMI) and height are associated with adult RCC. The study included 301,418 children (152,569 boys) from the Copenhagen School Health Records Register born 1930-1985 with measured weights and heights at ages 7 to 13 years. Birth weight was obtained by parental report. BMI and height were transformed to z-scores, and BMI was categorized as normal BMI or overweight. RCC was identified by linkage to the Danish Cancer Registry. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated by Cox proportional hazards regression. During follow-up, 1010 individuals (680 men) were diagnosed with RCC. BMI and height were positively associated with RCC with no significant sex-differences (age 13: HR = 1.14, 95% CI 1.06-1.23 per BMI z-score, HR = 1.12, 95% CI 1.05-1.20 per height z-score). Compared to children with normal BMI at ages 7 and 13 years, children with overweight only at age 13 had higher risks of RCC (HR = 1.67, 95% CI 1.24-2.26). Compared to children with average growth in height, persistently taller-than-average children (HR = 1.06, 95% CI 1.03-1.10) and children who changed from average to above-average height (HR = 1.08, 95% CI 1.01-1.15) had increased risks of RCC. Birth weight was positively associated with RCC (HR = 1.12, 95% CI 1.05-1.20 per 500 grams). Birth weight, childhood BMI and height were positively associated with RCC risk in men and women.

Smallpox and BCG vaccination in childhood and cutaneous malignant melanoma in Danish adults followed from 18 to 49 years.

BACKGROUND: Early smallpox and Bacillus Calmette-Guérin (BCG) vaccinations have been associated with reduced risk of cutaneous malignant melanoma (CMM). We assessed the association between pre-school smallpox vaccination and early-school BCG vaccination and CMM in a young Danish population. METHODS: We conducted a register-based case-cohort study of individuals growing up during the phase-out period of smallpox and BCG vaccination in Denmark (born 1965-1976) utilising the decrease in vaccination during this period. Information on childhood vaccinations and potential confounders from Copenhagen school health records were linked with nationwide registers on cancer (CMM diagnoses), migrations and deaths by personal identification numbers. RESULTS: The individuals were followed from age 18 until 31/12/2014 (maximum age at end of follow-up, 49 years). 188 cases of CMM occurred in the background population of 46,239 individuals; 172 CMM cases (91%) had full information and were analysed. The adjusted hazard ratio (HR) for CMM by BCG and/or smallpox vaccination compared with neither vaccine was 1.29 (95% confidence interval (CI) 0.72-2.31). For smallpox vaccination only, HR = 1.23 (95% CI 0.53-2.86) for BCG vaccination only, HR = 1.13 (95% CI 0.61-2.09) and for both smallpox and BCG vaccination, HR = 1.75 (95% CI 0.87-3.48) compared with none of these. Vaccination below the age of one year gave similar results. CONCLUSIONS: We found no strong beneficial effect of smallpox and BCG vaccination against CMM among young adult Danes and with broad confidence intervals our data alone could be compatible with both modest preventive effects, no effects, and modest harmful effects. Our estimates do not contradict a potential modest beneficial effect of neonatal vaccination.

Childhood Stature and Growth in Relation to First Ischemic Stroke or Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: Attained height, an indicator of genetic potential and childhood growth environment, is inversely associated with stroke, but the mechanisms are poorly understood. We investigated whether childhood height and growth are associated with ischemic stroke (IS) and intracerebral hemorrhage (ICH). METHODS: In a cohort of Danish schoolchildren born 1930 to 1989, with measured height from 7 to 13 years, we investigated associations of childhood stature and growth with risks of adult IS and ICH. Cox proportional hazards regressions were performed to estimate hazard ratios (HRs) with CIs separately for women and men. RESULTS: Among 311 009 individuals, 10 412 were diagnosed with IS and 2546 with ICH. Height at 7 years was inversely and significantly associated with IS in both sexes (per z score, equivalent to ≈5.2 cm in women and 5.1 cm in men; women: HR=0.89 [95% CI: 0.87-0.92]; men: HR=0.90 [95% CI: 0.88-0.92]) and with ICH in men (HR=0.89 [95% CI: 0.84-0.94]) but not in women (HR=0.97 [95% CI: 0.91-1.04]). Associations were similar at older childhood ages and were stable throughout the study period. No statistically significant associations for growth from 7 to 13 years were observed for IS or ICH. CONCLUSIONS: Short stature at 7 to 13 years is significantly associated with increased risks of IS in both sexes and with ICH in men. Growth during this period of childhood is not significantly associated with either of these stroke subtypes, suggesting that underlying mechanisms linking height with risks of stroke may exert their influence already by early childhood.

The Effect of Smallpox and Bacillus Calmette-Guérin Vaccination on the Risk of Human Immunodeficiency Virus-1 Infection in Guinea-Bissau and Denmark.

BACKGROUND: The live smallpox and Bacillus Calmette-Guérin (BCG) vaccinations have been associated with better adult survival in both Guinea-Bissau and Denmark. In Guinea-Bissau, human immunodeficiency virus (HIV)-1 became an important cause of death after smallpox vaccination was phased out globally in 1980. We hypothesised that smallpox and BCG vaccinations were associated with a lower prevalence of HIV-1 infection, and we tested this hypothesis in both Guinea-Bissau and Denmark. METHODS: We conducted 2 studies: (1) a cross-sectional study of HIV infection and vaccination scars in Guinea-Bissau including 1751 individuals and (2) a case-base study with a background population of 46239 individuals in Denmark. In Guinea-Bissau, HIV-1 transmission was almost exclusively sexually transmitted. In Denmark, we excluded intravenous drug users. Data were analyzed using logistic regression. RESULTS: Bacillus Calmette-Guérin and/or smallpox vaccination compared with neither of these vaccines was associated with an adjusted odds ratio (aOR) for HIV-1 of 0.62 (95% confidence interval [CI], 0.36-1.07) in Guinea-Bissau and 0.70 (95% CI, 0.43-1.15) in Denmark. We combined the results from both settings in a meta-analysis (aOR = 0.66; 95% CI, 0.46-0.96). Data from Guinea-Bissau indicated a stronger effect of multiple smallpox vaccination scars (aOR = 0.27; 95% CI, 0.10-0.75) as follows: women, aOR = 0.18 (95% CI, 0.05-0.64); men, aOR = 0.52 (95% CI, 0.12-2.33); sex-differential effect, P = .29. CONCLUSIONS: The studies from Guinea-Bissau and Denmark, 2 very different settings, both suggest that the BCG and smallpox vaccines could be associated with a decreased risk of sexually transmitted HIV-1. It might be informative to pursue this observation and explore possible protective mechanisms as part of the search for an HIV-1 vaccine.

A Proposal of the European Association for the Study of Obesity to Improve the ICD-11 Diagnostic Criteria for Obesity Based on the Three Dimensions Etiology, Degree of Adiposity and Health Risk.

Diagnostic criteria for complex medical conditions caused by a multitude of both genetic and environmental factors should be descriptive and avoid any attribution of causality. Furthermore, the wording used to describe a disorder should be evidence-based and avoid stigmatization of the affected individuals. Both terminology and categorizations should be readily comprehensible for healthcare professionals and guide clinical decision making. Uncertainties with respect to diagnostic issues and their implications may be addressed to direct future clinical research. In this context, the European Association of the Study of Obesity (EASO) considers it an important endeavor to review the current ICD-11 Beta Draft for the definition of overweight and obesity and to propose a substantial revision. We aim to provide an overview of the key issues that we deem relevant for the discussion of the diagnostic criteria. We first discuss the current ICD-10 criteria and those proposed in the ICD 11 Beta Draft. We conclude with our own proposal for diagnostic criteria, which we believe will improve the assessment of patients with obesity in a clinically meaningful way.

[The implications of using different body mass index references in children and adolescents].

To classify children as overweight or obese, their body mass index (BMI) must be compared with a growth reference and be accompanied by a clinical assessment. In Denmark, there is a lack of consensus on which BMI reference to use; a mix of national and international references are used in clinics, hospitals and research institutions. In this article, the implications of using different references are illustrated with Danish data. The comparisons show that the references yield different prevalences of overweight in a non-predictable way, making comparisons and monitoring challenging.

A hospital-based child and adolescent overweight and obesity treatment protocol transferred into a community healthcare setting.

BACKGROUND: Due to the pandemic of child and adolescent overweight and obesity, improvements in overweight and obesity treatment availability and accessibility are needed. METHODS: In this prospective study, we investigated if reductions in body mass index (BMI) standard deviation scores (SDS) and waist circumference (WC) would occur during 1.5 years of community-based overweight and obesity treatment based upon an effective hospital-based overweight and obesity treatment protocol, The Children's Obesity Clinics' Treatment protocol. Height, weight, and WC were measured at all consultations. Changes in BMI SDS and WC were analyzed using linear mixed models based upon the repeated measures in each child. RESULTS: From June 2012 to January 2015, 1,001 children (455 boys) were consecutively enrolled in the community-based treatment program. Upon entry, the median age was 11 years (range: 3-18), and the median BMI SDS was 2.85 (range: 1.26-8.96) in boys and 2.48 (range: 1.08-4.41) in girls. After 1.5 years of treatment BMI SDS was reduced in 74% of the children. BMI SDS was reduced by a mean of 0.38 (95% confidence interval (CI): 0.30-0.45, p<0.0001) in boys and 0.18 (95% CI: 0.12-0.25, p<0.0001) in girls after 1.5 years of treatment, independently of baseline age, BMI SDS, and Tanner stage (all p>0.08). WC was reduced by a mean of 3.8 cm (95% CI: 2.7-4.9, p>0.0001) in boys and 5.1 cm (95% CI: 4.0-6.2, p>0.0001) in girls. The dropout rate was 31% after 1.5 years. A median of 4.5 consultation hours was invested per child per year. CONCLUSION: BMI SDS and WC were reduced after 1.5 years of treatment. Hence, this community-based overweight and obesity treatment program may help accommodate the need for improvements in treatment availability and accessibility.

Variations in the Prevalence of Obesity Among European Countries, and a Consideration of Possible Causes.

Over the last 10 years the prevalence of obesity across the European continent has in general been rising. With the exception of a few countries where a levelling-off can be perceived, albeit at a high level, this upward trend seems likely to continue. However, considerable country to country variation is noticeable, with the proportion of people with obesity varying by 10% or more. This variation is intriguing and suggests the existence of different profiles of risk or protection factors operating in different countries. The identification of such protection factors could indicate suitable targets for interventions to help manage the obesity epidemic in Europe. This report is the output of a 2-day workshop on the 'Diversity of Obesity in Europe'. The workshop included 14 delegates from 12 different European countries. This report contains the contributions and discussions of the materials and viewpoints provided by these 14 experts; it is not the output of a single mind. However, such is the nature of scientific analysis regarding obesity that it is possible that a different set of 14 experts may have come to a different set of conclusions. Therefore the report should not be seen as a definitive statement of a stable situation. Rather it is a focus for discussion and comment, and a vehicle to drive forward further understanding and management of obesity in Europe.

Vaccinations against smallpox and tuberculosis are associated with better long-term survival: a Danish case-cohort study 1971-2010.

Background: When vaccinations with vaccinia against smallpox and Bacillus Calmette-Guérin (BCG) against tuberculosis were phased out in some high-income countries around 1980, the impact on overall mortality was not examined. Recent studies from low-income countries have suggested that these vaccines are associated with mortality reductions, not explained by specific disease protection. We examined whether vaccinia and BCG administered in childhood were associated with long-term mortality reductions in a high-income population. Methods: In this case-cohort study, we followed 47 622 schoolchildren from Copenhagen, Denmark, born 1965 to 1976, from their first health examination to 2010. This cohort experienced the phase-out of vaccinia and BCG vaccination programmes. Results: A sub-cohort of 5 316 individuals (699 excluded) was followed for 164 450 person-years (0.2% were lost to follow-up), and 401 deaths due to natural causes (841 deaths in total) occurred in the full cohort. Compared with individuals who had not received vaccinia or BCG, those who had received both vaccinia and BCG had an adjusted hazard ratio (aHR) of 0.54 [95% confidence interval (CI): 0.36-0.81] for mortality due to natural causes of death; those who only received BCG had an aHR of 0.58 (95% CI: 0.39-0.85). Vaccinia and BCG were not associated with any protection against deaths by accidents, suicide or murder, the combined aHR being 0.94 (95% CI: 0.62-1.42). Conclusions: Vaccinia and BCG vaccinations were associated with better long-term survival, which was not explained by specific protection. Vaccines with beneficial non-specific effects may reduce overall mortality even after the target diseases are eradicated.

Associations between childhood height and morphologically different variants of melanoma in adulthood.

AIM OF THE STUDY: Melanoma subtypes have different aetiological characteristics. Child height is positively associated with adult melanoma; however, a clarification of associations with specific melanoma variants is necessary for an improved understanding of risk factors underlying the histologic entities. This study investigated associations between childhood height and future development of cutaneous melanoma variants. METHOD: A cohort study of 316,193 individuals from the Copenhagen School Health Records Register, with measured heights at ages 7-13 years who were born from 1930 to 1989. Melanoma cases were identified via linkage to the national Danish Cancer Registry and subdivided into subtypes. Cox proportional hazards regressions were performed. RESULTS: A total of 2223 cases of melanoma distributed as 60% superficial spreading melanoma (SSM), 27.5% melanoma not otherwise specified (NOS), 8.5% nodular melanoma (NM), and 2% lentigo maligna melanoma (LMM). The remaining rare melanoma forms were not analysed. Childhood height was positively and significantly associated with SSM, melanoma NOS, and NM, but not LMM, in adulthood. Per height z-score at age 13 years, the hazard ratios were 1.20 (95% confidence intervals [CI]: 1.13-1.27) for SSM, 1.19 (95% CI: 1.09-1.29) for melanoma NOS, and 1.21 (95% CI: 1.04-1.41) for NM. Further, growth patterns were linked to the melanoma variants with persistently tall children having an increased risk of developing SSM, melanoma NOS, or NM. CONCLUSION: Childhood height is positively associated with the majority of the melanoma variants. These results suggest that the underlying processes contributing to childhood height and growth patterns interconnect early-life events with the predisposition to melanomagenesis in adulthood.

Ethnic Inequalities in Overweight and Obesity Prevalence among Copenhagen Schoolchildren from 2002 to 2007.

BACKGROUND: The stabilization in levels of childhood overweight has masked increasing gaps among different ethnic and socioeconomic groups in several countries. OBJECTIVE: To examine if levels and trends in childhood overweight and obesity differed by ethnicity and socioeconomic areas in Copenhagen schoolchildren. METHODS: From measured heights and weights of 32,951 children 5-8 and 14-16 years of age, the prevalence of overweight (including obesity) and obesity were estimated using International Obesity Task Force criteria. Differences in prevalence levels and trends across six school years by ethnicity and socioeconomic areas were examined using logistic regression. RESULTS: The prevalence of overweight significantly decreased from 2002 to 2007 among the youngest Western girls and boys, showed no significant changes among the oldest non-Western girls and increased among the oldest non-Western boys. In all years, the youngest non-Western children had significantly higher levels of overweight than Western children. Although the prevalence of overweight tended to be higher in low socioeconomic areas as compared with high socioeconomic areas, few differences were statistically significant. Consistent trends in overweight across the years by socioeconomic area were not observed. CONCLUSION: Ethnic and social inequalities exist in childhood overweight among Copenhagen schoolchildren; thus appropriate interventions targeting high-risk groups are needed.