Obesity treatment effect in Danish children and adolescents carrying Melanocortin-4 Receptor mutations.

OBJECTIVES: To determine the prevalence of Melanocortin-4 Receptor (MC4R) mutations in a cohort of children and adolescents with overweight or obesity and to determine whether treatment responses differed between carriers and noncarriers. METHODS: Using target region capture sequencing, an MC4R mutation screen was performed in 1261 Danish children and adolescents enrolled at a tertiary multidisciplinary childhood obesity treatment center. Measurements of anthropometrics, blood pressure, fasting blood biochemistry including lipid and hormone levels, and dual-energy X-ray absorptiometry were performed at baseline and throughout treatment. RESULTS: Of 1209 children and adolescents that met all criteria to be included in the described analyses, 30 (2.5%) carried damaging or unresolved MC4R mutations. At baseline, mutation carriers exhibited higher concentrations of plasma thyroid-stimulating hormone (p = 0.003), and lower concentrations of plasma thyroxine (p = 0.010) compared to noncarriers. After a median of 1 year of treatment (range 0.5-4.0 years), body mass index (BMI) standard deviation score (SDS) was reduced in noncarriers but not in carriers, and this difference in treatment response was statistically significant (p = 0.005). Furthermore, HDL cholesterol was reduced in carriers, a response significantly different from that of noncarriers (p = 0.017). CONCLUSION: Among Danish children and adolescents with overweight or obesity entering a tertiary lifestyle intervention, 2.5% carried damaging or unresolved MC4R mutations. In contrast to noncarriers, carriers of damaging or unresolved MC4R mutations failed to reduce their BMI SDS during obesity treatment, indicating a need for personalized treatment based on the MC4R genotype.

Childhood height and risk of testicular germ cell tumors in adulthood.

Increased adult stature has been associated with risk of testicular germ cell tumors (TGCT) in a number of studies. Whether childhood stature is also associated with TGCT is unclear as no studies of measured childhood height and TGCT have been reported. Thus, associations between TGCT in adulthood and childhood height and growth between ages 7 and 13 years were examined in a cohort from the Copenhagen School Health Records Register. Analyses included 162,607 boys born during the years 1930-1989. Development of TGCT was determined via linkage to the Danish Cancer Registry. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression. Between 1968 and 2014, 782 TGCT were diagnosed. Childhood height, per one unit increase in z-score, was associated with risk of TGCT, with HRs ranging from 1.11 (95%CI 1.03-1.20) at age 7 to 1.09 (95%CI = 1.01-1.18) at age 13. In a categorical analysis, the shortest boys were at the lowest risk of developing TGCT. Results varied little by TGCT histology (seminoma and nonseminoma). Growth between ages 7 and 13 years was not associated with risk. These findings suggest that risk of TGCT in adulthood was already determined by age 7 years. Although the mechanism requires further investigation, these results provide additional evidence that risk of TGCT is determined at a young age, thus suggesting that additional investigation of early life factors is warranted.

Childhood body mass index in relation to subsequent risk of type 1 diabetes-A Danish cohort study.

The incidence of type 1 diabetes (T1D) is increasing, and obesity may be a contributing factor by increasing the risk and accelerating the onset. We investigated the relation between childhood body mass index z-scores (BMIz) and the later risk of T1D, including association with age at onset of T1D. The study included 238 cases and 10 147 controls selected from the Copenhagen School Health Record Register (CSHRR). Cases of T1D were identified in the Danish Registry of Childhood and Adolescent Diabetes and 2 regional studies and linked to CSHRR. Using conditional logistic regression models, the association of childhood prediagnostic BMIz at 7 and 13 years of age and changes between these ages with subsequent risk (odds ratio, OR) of T1D was estimated. A greater BMIz at 7 and 13 years of age was associated with increased risk of T1D with OR of 1.23 (confidence interval, CI 1.09-1.37; P = .0001) and 1.20 (CI 1.04-1.40; P = .016), respectively. The risk was increased by upward changes in z-scores from birth to 7 years (OR=1.21, P = .003) and from 7 to 13 years of age (OR=1.95, P = .023), but in the latter age interval also by a decline in BMIz (OR = 1.91, P = .034). There were no associations between BMIz at 7 and 13 years of age and the age of onset (P = .34 and P = .42, respectively). Increased BMIz is associated with a moderate increase in risk of T1D, but with no relation to age at onset within the analyzed age range. Increased BMIz over time is unlikely to explain the rising incidence of T1D.

The effect of impaired glucose metabolism on weight loss in multidisciplinary childhood obesity treatment.

OBJECTIVE: To investigate whether children and adolescents exhibiting an impaired glucose metabolism are more obese at treatment entry and less likely to reduce their degree of obesity during treatment. METHODS: The present study is a longitudinal observational study, including children and adolescents from the Children's Obesity Clinic, Holbaek, Denmark. Anthropometrics, pubertal development, socioeconomic status (SES), and fasting concentrations of plasma glucose, serum insulin, serum C-peptide, and whole blood glycosylated hemoglobin (HbA1c) were collected at treatment entry and at follow-up. Proxies of Homeostasis Model Assessment 2-insulin sensitivity (HOMA2-IS) and Homeostasis Model Assessment 2-ß-cell function (HOMA2-B) were calculated with the Homeostasis Model Assessment 2 program. RESULTS: In total, 569 (333 boys) patients, median 11.5 years of age (range 6-22 years), and median body mass index (BMI) z-score 2.94 (range 1.34-5.54) were included. The mean BMI z-score reduction was 0.31 (±0.46) after 13 months (range 6-18) of treatment. At treatment entry, patients with impaired estimates of glucose metabolism were more obese than normoglycemic patients. Baseline concentration of C-peptide was associated with a lower weight loss during treatment in girls (P = .02). Reduction in the insulin concentrations was associated with reduction in BMI z-score in both sexes (P < .0001, P = .0005). During treatment, values of glucose, HbA1c, HOMA2-IS, and HOMA2-B did not change or impact the treatment outcome, regardless of age, sex, SES, or degree of obesity at treatment entry. CONCLUSION: The capability to reduce weight during multidisciplinary treatment in children and adolescents with overweight/obesity is not influenced by an impaired glucose metabolism at study entry or during the course of treatment.

Association of Childhood Body Mass Index and Change in Body Mass Index With First Adult Ischemic Stroke.

Importance: The incidence of ischemic stroke among young adults is rising and is potentially due to an increase in stroke risk factors occurring at younger ages, such as obesity. Objectives: To investigate whether childhood body mass index (BMI) and change in BMI are associated with adult ischemic stroke and to assess whether the associations are age dependent or influenced by birth weight. Design, Setting, and Participants: This investigation was a population-based cohort study of schoolchildren born from 1930 to 1987, with follow-up through national health registers from 1977 to 2012 in Denmark. Participants were 307 677 individuals (8899 ischemic stroke cases) with measured weight and height at ages 7 to 13 years. The dates of the analysis were September 1, 2015, to May 27, 2016. Main Outcomes and Measures: Childhood BMI, change in BMI, and birth weight. Ischemic stroke events were divided into early (≤55 years) or late (>55 years) age at diagnosis. Results: The study cohort comprised 307 677 participants (approximately 49% female and 51% male). During the study period, 3529 women and 5370 men experienced an ischemic stroke. At all ages from 7 to 13 years, an above-average BMI z score was positively associated with early ischemic stroke. At age 13 years, a BMI z score of 1 was associated with hazard ratios (HRs) of 1.26 (95% CI, 1.11-1.43) in women and 1.21 (95% CI, 1.10-1.33) in men. No significant associations were found for below-average BMI z scores. Among children with above-average BMI z scores at age 7 years, a score increase of 0.5 from ages 7 to 13 years was positively associated with early ischemic stroke in women (HR, 1.10; 95% CI, 1.01-1.20) and in men (HR, 1.08; 95% CI, 1.00-1.16). Similarly, among children with below-average BMI z scores at age 7 years, a score increase of 0.5 from ages 7 to 13 years was positively associated with early ischemic stroke in women (HR, 1.14; 95% CI, 1.06-1.23) and in men (HR, 1.10; 95% CI, 1.04-1.18). Adjusting for birth weight minimally affected the associations. Conclusions and Relevance: Independent of birth weight, above-average childhood BMI and increases in BMI during childhood are positively associated with early adult ischemic stroke. To avoid the occurrence of early ischemic stroke associated with childhood overweight and obesity, these results suggest that all children should be helped to attain and maintain healthy weights.

Childhood body mass index and height in relation to site-specific risks of colorectal cancers in adult life.

As colorectal cancers have a long latency period, their origins may lie early in life. Therefore childhood body mass index (BMI; kg/m2) and height may be associated with adult colorectal cancer. Using a cohort design, 257,623 children from The Copenhagen School Health Records Register born from 1930 to 1972 with measured heights and weights at ages 7 to 13 years were followed for adult colon and rectal adenocarcinomas by linkage to the Danish Cancer Registry. Hazard ratios (HRs) with 95% confidence intervals (CI) were estimated by Cox proportional hazard regressions. During follow-up, 2676 colon and 1681 rectal adenocarcinomas were diagnosed. No sex differences were observed in the associations between child BMI or height and adult colon or rectal cancers. Childhood BMI and height were positively associated with colon cancer; at age 13 years the HRs were 1.09 (95% CI 1.04-1.14) and 1.14 (95% CI 1.09-1.19) per z-score, respectively. Children who were persistently taller or heavier than average, had increased risk of colon cancer. Similarly, growing taller or gaining more weight than average was positively associated with colon cancer. No associations were observed between BMI or height and rectal cancer. Childhood BMI and height, along with above average change during childhood are significantly and positively associated with adult colon cancers, but not with rectal cancer, suggesting different etiologies.

Childhood Body Size and the Risk of Malignant Melanoma in Adulthood.

Malignant melanoma (MM) is the most aggressive form of skin cancer. Adult anthropometry influences MM development; however, associations between childhood body size and future melanomagenesis are largely unknown. We investigated whether height, body mass index (BMI; weight (kg)/height (m)2), and body surface area (BSA) at ages 7-13 years and birth weight are associated with adult MM. Data from the Copenhagen School Health Records Register, containing annual height and weight measurements of 372,636 Danish children born in 1930-1989, were linked with the Danish Cancer Registry. Cox regression analyses were performed. During follow-up, 2,329 MM cases occurred. Height at ages 7-13 years was significantly associated with MM, even after BMI and BSA adjustments. No significant BMI-MM or BSA-MM associations were detected when adjusting for height. Children who were persistently tall at both age 7 years and age 13 years had a significantly increased MM risk compared with children who grew taller between those ages. Birth weight was positively associated with MM. We conclude that associations between body size and MM originate early in life and are driven largely by height and birth weight, without any comparable influence of BMI or BSA. Melanoma transformation is unlikely to be due to height per se; however, height-regulating processes in childhood present new areas for mechanistic explorations of this disease.

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.

Childhood body mass index and development of type 2 diabetes throughout adult life-A large-scale danish cohort study.

OBJECTIVE: This study investigated how a wide spectrum of body mass index (BMI) values at ages 7 to 13 years are associated with type 2 diabetes throughout adulthood, including potential modifying effects of sex and birth weight. METHODS: From the Copenhagen School Health Records Register, 292,827 individuals, born between 1930 and 1989, were followed in national registers for type 2 diabetes (women, n = 7,472; men, n = 11,548). Heights and weights were measured at ages 7 to 13 years. RESULTS: Below-average BMIs, with few exceptions, were not associated with type 2 diabetes. Above-average BMIs had positive associations that were stronger in women than men, stronger in younger birth cohorts, and weaker with older age at diagnosis. Women born 1930-1947, 1948-1965, and 1966-1983 with above-average BMIs at 13 years (≥18.2 kg/m2 ) had hazard ratios (95% confidence intervals) ranging from 2.12 (1.91-2.36) to 2.84 (2.31-3.49) per z score when diagnosed at 30 to 47 years. Birth weight did not modify these associations. CONCLUSIONS: Childhood BMIs below average are not associated with type 2 diabetes, whereas childhood BMIs above average are strongly associated with type 2 diabetes in adulthood, corresponding to excess risks even at levels below international definitions of overweight. The associations are stronger in women than men but are not affected by birth weight.

Childhood body mass index and risk of adult pancreatic cancer.

BACKGROUND: Excess weight in adulthood is one of the few modifiable risk factors for pancreatic cancer, and height has associations as well. This leads to question whether body weight and height in childhood are associated with adult pancreatic cancer. OBJECTIVE: To examine if childhood body mass index (BMI; kg/m2) and height are associated with pancreatic cancer in adult life. METHODS: We linked 293,208 children born from 1930-1982 in the Copenhagen School Health Records Register who had measured values of weights and heights at ages 7-13 years with the Danish Cancer Registry to identify incident pancreatic cancer cases from 1968-2012. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional hazard regressions. RESULTS: During 8,207,015 person-years of follow-up, 1,268 pancreatic cancer cases were diagnosed. Childhood BMI z-scores at ages 7-13 years were positively and significantly associated with pancreatic cancer in men and women up to age 70 years; beyond age 70 the associations diminished. The HRs of pancreatic cancer were 1.13 (95% CI: 1.05-1.21) and 1.18 (95% CI: 1.09-1.27) per BMI z-score at ages 7 and 13 years, respectively. A BMI ≥1.5 z-score at ages 7, 10 and 13 years was positively and significantly associated with pancreatic cancer; however, the effect did not differ from having a BMI z-score ≥1.5 at only one of these ages. Positive, albeit non-statistically significant, associations were identified with height. CONCLUSIONS: BMI at all ages from 7-13 years is positively and linearly associated with adult pancreatic cancer; the higher the BMI, the higher the risk. Excess childhood BMI may be indicative of processes initiated early in life that lead to this cancer. Prevention of childhood adiposity may decrease the burden of pancreatic cancer in adults.

Childhood body mass index growth trajectories and endometrial cancer risk.

Previously, we found that excess weight already in childhood has positive associations with endometrial cancer; however, associations with changes in body mass index (BMI) during childhood are not well understood. Therefore, we examined whether growth in childhood BMI is associated with endometrial cancer and its sub-types. A cohort of 155,505 girls from the Copenhagen School Health Records Register with measured weights and heights at the ages of 6-14 years and born 1930-1989 formed the analytical population. BMI was transformed to age-specific z scores. Using linear spline multilevel models, each girl's BMI growth trajectory was estimated as the deviance from the average trajectory for three different growth periods (6.25-7.99, 8.0-10.99, 11.0-14.0 years). Via a link to health registers, 1,020 endometrial cancer cases were identified, and Cox regressions were performed. A greater gain in BMI during childhood was positively associated with endometrial cancer but no differences between the different growth periods were detected in models adjusted for baseline BMI. The hazard ratios for the associations with overall growth during childhood per 0.1 z score increase were 1.15 (95% confidence interval [CI]: 1.07-1.24) for all endometrial cancers, 1.12 (95% CI: 1.04-1.21) for estrogen-dependent cancers, 1.16 (95% CI: 1.06-1.26) for endometrioid adenocarcinomas and 1.46 (95% CI: 1.16-1.84) for non-estrogen-dependent cancers. Growth in BMI in early life is positively linked to later endometrial cancer risk. We did not identify any sensitive childhood growth period, which suggests that excess gain in BMI during the entire childhood period should be avoided.

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.

Comparison of sensory-specific satiety between normal weight and overweight children.

Sensory properties of some foods may be of importance to energy consumption and thus the development and maintenance of childhood obesity. This study compares selected food related qualities in overweight and normal weight children. Ninety-two participants were included; 55 were overweight with a mean age of 11.6 years (range 6-18 years) and a mean BMI z-score of 2.71 (range 1.29-4.60). The 37 normal weight children had a mean age of 13.0 years (range 6-19 years) and a mean BMI z-score of 0.16 (range -1.71 to 1.24). All children completed a half-hour long meal test consisting of alternation between consumption of foods and answering of questionnaires. Compared to the normal weight, the overweight children displayed lower self-reported intake paces (χ2(2) = 6.3, p = 0.04), higher changes in liking for mozzarella (F(1,63) = 9.55, p = 0.003) and pretzels (F(1,87) = 5.27, p = 0.024), and declines in wanting for something fat, of which the normal weight children displayed an increase (F(1,83) = 4,10, p = 0.046). No differences were found for sensory-specific satiety, wanting for the main food yoghurt, hunger, or satiety. In conclusion, overweight children did not differ from normal weight children in terms of sensory-specific satiety, hunger, or satiety. However, overweight children had lower intake paces and appeared to differ from normal weight children regarding foods with a fatty taste.

Associations between birth weight and colon and rectal cancer risk in adulthood.

BACKGROUND: Birth weight has inconsistent associations with colorectal cancer, possibly due to different anatomic features of the colon versus the rectum. The aim of this study was to investigate the association between birth weight and colon and rectal cancers separately. METHODS: 193,306 children, born from 1936 to 1972, from the Copenhagen School Health Record Register were followed prospectively in Danish health registers. Colon and rectal cancer cases were defined using the International Classification of Disease version 10 (colon: C18.0-18.9, rectal: 19.9 and 20.9). Only cancers classified as adenocarcinomas were included in the analyses. Cox regressions were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). Analyses were stratified by birth cohort and sex. RESULTS: During 3.8 million person-years of follow-up, 1465 colon and 961 rectal adenocarcinomas were identified. No significant sex differences were observed; therefore combined results are presented. Birth weight was positively associated with colon cancers with a HR of 1.14 (95% CI, 1.04-1.26) per kilogram of birth weight. For rectal cancer a significant association was not observed for birth weights below 3.5kg. Above 3.5kg an inverse association was observed (at 4.5kg, HR=0.77 [95% CI, 0.61-0.96]). Further, the associations between birth weight and colon and rectal cancer differed significantly from each other (p=0.006). CONCLUSIONS: Birth weight is positively associated with the risk of adult colon cancer, whereas the results for rectal cancer were inverse only above values of 3.5kg. The results underline the importance of investigating colon and rectal cancer as two different entities.

Childhood height, adult height, and the risk of prostate cancer.

PURPOSE: We previously showed that childhood height is positively associated with prostate cancer risk. It is, however, unknown whether childhood height exerts its effects independently of or through adult height. We investigated whether and to what extent childhood height has a direct effect on the risk of prostate cancer apart from adult height. METHODS: We included 5,871 men with height measured at ages 7 and 13 years in the Copenhagen School Health Records Register who also had adult (50-65 years) height measured in the Danish Diet, Cancer and Health study. Prostate cancer status was obtained through linkage to the Danish Cancer Registry. Direct and total effects of childhood height on prostate cancer risk were estimated from Cox regressions. RESULTS: From 1996 to 2012, 429 prostate cancers occurred. Child and adult heights were positively and significantly associated with prostate cancer risk. When adjusted for adult height, height at age 7 years was no longer significantly associated with the risk of prostate cancer. Height at 13 years was significantly and positively associated with prostate cancer risk even when adult height was adjusted for; per height z-score the hazard ratio was 1.15 [95% confidence interval (CI) 1.01-1.32]. CONCLUSIONS: The effect of height at 13 years on the risk of prostate cancer was not entirely mediated through adult height, suggesting that child height and adult height may be associated with prostate cancer through different pathways.

Sex-specific associations between birth weight and adult primary liver cancer in a large cohort of Danish children.

Whether the prenatal period is critical for the development of adult primary liver cancer (PLC) is sparsely investigated. Recently, attention has been drawn to potential sex-differences in the early origins of adult disease. The association between birth weight and adult PLC, separately in men and women was investigated, using a large cohort of 217,227 children (51% boys), born from 1936 to 1980, from the Copenhagen School Health Records Register, and followed them until 2010 in national registers. Hazard ratios (95% confidence intervals) of PLC (30 years or older) were estimated by Cox regression models stratified by birth cohort. During 5.1 million person-years of follow-up, 185 men and 65 women developed PLC. Sex modified the association between birth weight and adult PLC (p values for interaction = 0.0005). Compared with a sex-specific reference group of birth weights between 3.25 and 3.75 kg, men with birth weights between 2.00 and 3.25 kg and 3.75-5.50 kg, had HRs of 1.48 (1.06-2.05) and 0.85 (0.56-1.28), respectively. Among women the corresponding HRs were 1.71 (0.90-3.29) and 3.43 (1.73-6.82). Associations were similar for hepatocellular carcinoma only, across year of birth, and after accounting for diagnoses of alcohol-related disorders, viral hepatitis and biliary cirrhosis. Prenatal exposures influenced the risk of adult PLC, and the effects at the high birth weight levels appeared to be sex-specific. These findings underscore the importance of considering sex-specific mechanisms in the early origins of adult PLC.

Comparison of birth weight between school health records and medical birth records in Denmark: determinants of discrepancies.

OBJECTIVE: To compare reported birth weight (BW) information in school health records with BW from medical birth records, and to investigate if maternal and offspring characteristics were associated with any discrepancies. DESIGN: Register-based cohort study. SETTING: Denmark, 1973-1991. PARTICIPANTS: The study was based on BW recorded in the Copenhagen School Health Records Register (CSHRR) and in The Medical Birth Register (MBR). The registers were linked via the Danish personal identification number. PRIMARY AND SECONDARY OUTCOME MEASURES: Statistical comparisons of BW in the registers were performed using t tests, Pearson's correlation coefficients, Bland-Altman plots and κ coefficients. Odds of BW discrepancies >100 g were examined by logistic regressions. RESULTS: The study population included 47,534 children. From 1973 to 1979 when BW was grouped in 500 g intervals in the MBR, mean BW differed significantly between the registers. During 1979-1991 when BW was recorded in 10 and 1 g intervals, mean BW did not significantly differ between the two registers. BW from both registers was highly correlated (0.93-0.97). Odds of a BW discrepancy significantly increased with parity, the child's age at recall and by marital status (children of married women had the highest odds). CONCLUSIONS: Overall, BW information in school health records agreed very well with BW from medical birth records, suggesting that reports of BWs in school health records in Copenhagen, Denmark generally are valid.

Sex Differences in the Association Between Birth Weight and Adult Type 2 Diabetes.

Low birth weight is a well-established risk factor for type 2 diabetes, but the risk at high birth weight levels remains uncertain. Potential sex differences in the associations are unexplored. We investigated whether sex influences the association of birth weight and adult type 2 diabetes, using a cohort of 113,801 men and 109,298 women, born 1936-1983, from the Copenhagen School Health Records Register, Denmark. During 5.6 million person-years of follow-up, 7,750 men and 4,736 women had a diagnosis of adult type 2 diabetes (30 years of age or older) obtained from national registers. When birth weights between 3.251 and 3.750 kg were used as the reference group for each sex separately, women with birth weights in the categories of 2.000 to 2.750 kg and 4.751 to 5.500 kg had hazard ratios [HRs] of type 2 diabetes of 1.46 (95% CI, 1.34-1.59) and 1.56 (1.20-2.04), respectively, whereas men had HRs of 1.20 (1.12-1.30) and 0.93 (0.76-1.15). Thus, sex modified the association, with stronger risk estimates of type 2 diabetes in women at both low and high birth weights compared with men (P = 0.001). In conclusion, birth weight is more strongly associated with type 2 diabetes in women than in men. Future search for sex-specific causal mechanisms may provide new insights into the early origins of type 2 diabetes.

No evidence of seasonality of birth in adult type 2 diabetes in Denmark.

AIMS/HYPOTHESIS: The season of birth might influence prenatal circumstances, which may influence the risk of developing type 2 diabetes. The aim of this study was to determine whether the diagnosis of type 2 diabetes in Denmark changed with the season of birth. METHODS: This study used data from the population-based Copenhagen School Health Records Register (CSHRR) that includes schoolchildren born between 1930 and 1989. Via a personal identification number, the CSHRR was linked to the National Patient Register containing hospital discharge diagnoses since 1977. The effect of seasonal variation in birth on the risk of type 2 diabetes was assessed using Cox regression, with month or season of birth as the predictor. The underlying time variable was age, and follow-up started in 1977 or at age 30 years. RESULTS: The study population consisted of 223,099 people, of whom 12,486 developed adult type 2 diabetes. Using January as the reference month, the risk of type 2 diabetes by month of birth was not statistically different for any of the 11 comparative birth months. Grouping month of birth into seasons (spring was the reference) gave essentially similar results, showing no difference in the risk of type 2 diabetes for any season. Repeating the analysis by sex, birth cohort and birthweight categories revealed no associations. CONCLUSIONS/INTERPRETATION: The risk of adult type 2 diabetes was not associated with month of birth in a large Danish population-based study. The results suggest that the causes of seasonality in birthweight are not causes of type 2 diabetes.

Body mass index in school-aged children and the risk of routinely diagnosed non-alcoholic fatty liver disease in adulthood: a prospective study based on the Copenhagen School Health Records Register.

OBJECTIVE: The relation between childhood overweight and adult non-alcoholic fatty liver disease (NAFLD) is largely unknown. We investigated if weight and weight gain in childhood increases the risk of being diagnosed with NAFLD in routine clinical settings in adulthood. PARTICIPANTS: We studied 244,464 boys and girls, born between 1930 and 1989, who attended school in Copenhagen, Denmark. Their heights and weights were measured by physicians or nurses at mandatory school health examinations at ages 7-13 years. Body mass index (BMI) z-scores were calculated from an internal age-specific and sex-specific reference. OUTCOME MEASURES: NAFLD reported in the National Patient Register and the National Register of Pathology at 18 years of age or older. HRs with 95% CIs were estimated. RESULTS: During follow-up, 1264 and 1106 NAFLD cases, respectively, occurred in men and women. In both sexes, childhood BMI z-score was not consistently associated with adult NAFLD. Change in BMI z-score between 7 and 13 years of age was positively associated with NAFLD in both sexes. When adjusted for BMI z-score at age 7 years, the HRs of adult NAFLD were 1.15 (95% CI 1.05 to 1.26) and 1.12 (95% CI 1.02 to 1.23) per 1-unit gain in BMI z-score in men and women, respectively. Associations were similar when adjusted for BMI z-score at age 13 years, and were consistent across birth years. CONCLUSIONS: A BMI gain in school-aged children is associated with adult NAFLD. Intriguingly, BMI gain appears to have an effect on adult NAFLD irrespective of either the initial or the attained BMI. Taken together, our results suggest that BMI gain in childhood, rather than the level of BMI per se, is important in the development of adult NAFLD.