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PDF - 76KB, Supplementary Table 1. Birth weight and height of boys by age of assessment and by birth cohort. Supplementary Table 2. Hazard ratios of prostate cancer in adulthood per 1 kg in birth weight or per 5 cm in height. Supplementary Table 3. Test of proportional hazards assumption by inclusion of a time (age) varying effect of birth weight/childhood height on the risk of prostate cancer, measured as hazard ratio per z-score, in Cox proportional hazards regression models. Supplementary Table 4. Test of proportional hazards assumption by inclusion of a time (age) - birth weight/height z-score cross product term in Cox proportional hazards regression models. Age is divided into quartiles. Supplementary Table 5. Hazard ratios of prostate cancer in adulthood per increase in age-specific height z-score restricted to those with birth weight measures, unadjusted and adjusted for birth weight.

Background: Adult height has been positively associated with prostate cancer risk. However, the exposure window of importance is currently unknown and assessments of height during earlier growth periods are scarce. In addition, the association between birth weight and prostate cancer remains undetermined. We assessed these relationships in a cohort of the Copenhagen School Health Records Register (CSHRR).Methods: The CSHRR comprises 372,636 school children. For boys born between the 1930s and 1969, birth weight and annual childhood heights—measured between ages 7 and 13 years—were analyzed in relation to prostate cancer risk. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI).Results: There were 125,211 males for analysis, 2,987 of who were subsequently diagnosed with prostate cancer during 2.57 million person-years of follow-up. Height z-score was significantly associated with prostate cancer risk at all ages (HRs, 1.13 to 1.14). Height at age 13 years was more important than height change (P = 0.024) and height at age 7 years (P = 0.024), when estimates from mutually adjusted models were compared. Adjustment of birth weight did not alter the estimates. Birth weight was not associated with prostate cancer risk.Conclusions: The association between childhood height and prostate cancer risk was driven by height at age 13 years.Impact: Our findings implicate late childhood, adolescence, and adulthood growth periods as containing the exposure window(s) of interest that underlies the association between height and prostate cancer. The causal factor may not be singular given the complexity of both human growth and carcinogenesis. Cancer Epidemiol Biomarkers Prev; 22(12); 2232–40. ©2013 AACR.

PDF - 73KB, Supplementary Figure 1. Flow chart of eligible and included subjects for analyses that included birth weight. Supplementary Figure 2. Distribution of cases by age at diagnosis Supplementary Figure 3. Incidence rate of prostate cancer by age of diagnosis Supplementary Figure 4. Illustration of the restricted cubic spline model at: (A) 7 years; (B) 13 years

PDF file 75K, Supplementary Table 1. Hazard ratios and 95% confidence intervals for papillary and follicular thyroid cancer per 1-standard deviation score difference in height and BMI at each age from 7-13 years Supplementary Table 2. Hazard ratios and 95% confidence intervals for total thyroid cancer per 1-standard deviation score difference in height at each age from 7-13 years, by age at diagnosis Supplementary Table 3. Hazard ratios and 95% confidence intervals for total thyroid cancer per 1-standard deviation score difference in BMI at each age from 7-13 years, by age at diagnosis Supplementary Table 4. Hazard ratios and 95% confidence intervals for total thyroid cancer per 1-standard deviation score difference in height and BMI at each age from 7-13 years, mutually adjusted Supplementary Table 5. Hazard ratios and 95% confidence intervals for total thyroid cancer per 1-standard deviation score difference in height and BMI at each age from 7-13 years, restricted to participants with data on birth weight Supplementary Table 6. Hazard ratios of thyroid cancer by quintiles of change in height SDS between ages 7 and 13 years Supplementary Table 7. Hazard ratios of thyroid cancer by quintiles of change in BMI SDS between ages 7 and 13 years

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.

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.

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.

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.

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.

SummaryBackground Increased consumption of sweetened beverages has previously been linked to the degree of childhood obesity. Objective The aim of the present study was to assess whether the intake of sweetened beverages, candy, snacks or fast food at baseline in a multidisciplinary childhood obesity treatment program was associated with the baseline degree of obesity or the treatment effect. Methods This prospective study included 1349 overweight and obese children (body mass index standard deviation scores (BMI SDS) ≥ 1.64) enrolled in treatment at The Children's Obesity Clinic, Copenhagen University Hospital Holbaek. The children were evaluated at baseline and after up to 5.9 years of treatment (median 1.3 years). Results Both boys and girls decreased their BMI SDS during treatment with a mean decrease in boys of 0.35 (p

Childhood leanness is associated with an increased risk of schizophrenia, but the effects of gender, age at anthropometric measurements and age at first diagnosis on this relationship are unclear. The present study aimed at elucidating these associations.MethodsPopulation-based cohort study with childhood anthropometric measures obtained annually from the age of 7 to 13 years in 253,353 Danes born 1930–1976 and followed to 31 December 2010. During this period, 4936 were registered with schizophrenia. The associations of childhood BMI with risk of schizophrenia were estimated with Cox regression models.ResultsChildhood BMI was significantly inversely associated with risk of schizophrenia, however with different patterns among boys and girls. In boys, childhood BMI had an inverse non-linear association with schizophrenia risk dependent on age at diagnosis; in particular, a surprisingly strong association was found between leanness and later onset of schizophrenia. In girls, the risk of schizophrenia decreased linearly with increasing BMI z-score (HR: 0.93; 95% CI: 0.88–0.98). In both boys and girls, birth weight was inversely associated with later risk. In girls, but not in boys, birth weight appeared to significantly modify the associations; there was a somewhat stronger inverse association in the lowest birth weight category.ConclusionsBirth weight as well as childhood BMI at ages 7 through 13 years is associated with risk of schizophrenia in both genders, but with a particular high risk of late-onset in lean boys irrespective of birth weight, and in lean girls with low birth weight. If replicated, these observations may inform preventive efforts build on schizophrenia trajectories rooted in early life.

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., Highlights • Childhood height was positively and significantly associated with the majority of melanoma subtypes. • Diverse growth patterns in childhood were differentially associated with future melanomagenesis. • Height and melanoma risk may be linked by biological mechanisms, and these remain to be elucidated.

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.

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.

BACKGROUND: Many environmental factors have been shown to influence birth weight (BW) and one of these are season of birth.AIM: The aim of the present study was to investigate the seasonal variation in BW in Denmark during 1936-1989, and to see if the variation could be explained by sunshine exposure during pregnancy.METHODS: The study population was selected from the Copenhagen School Health Records Register and included 276 339 children born between 1936 and 1989. Seasonal variation was modeled using a non-stationary sinusoidal model that allowed the underlying trend in BW and the amplitude and phase of the yearly cycles to change.RESULTS: There was a clear seasonal pattern in BW which, however, changed gradually across the study period. The highest BWs were seen during fall (September - October) from 1936 to 1963, but a new peak gradually grew from the early 1940s during early summer (May - June) and became the highest from 1964 to 1989. The amplitude of the fall peak started at 25.5 (95%CI 24.6; 25.9) grams and gradually disappeared. The amplitude of the early summer peak gradually arose from nothing to a peak of 18.6 (95%CI 17.7; 19.6) grams in the mid 1980s where it started to decrease again. Sunshine did not explain the seasonal variation in BW.CONCLUSION: There was a clear seasonal pattern in BW in Denmark 1936-1989, which however changed across the study period. Throughout the study period we observed a peak in BW during the fall, but gradually, starting in the early 1940s, an additional early summer peak emerged and became the highest from 1964 and onwards.

Background: Middle-aged obese adults are at substantially elevated risk of oesophageal adenocarcinoma. It is unclear whether this risk originates earlier in life. Methods: We assessed associations between childhood body mass index (BMI) and height—measured annually between ages 7 and 13—with adult oesophageal adenocarcinoma in a cohort from the Copenhagen School Health Records Register. Analyses included 255 053 children born during 1930–1971. Danish Cancer Registry linkage provided outcomes. We calculated hazard ratios (HRs) and 95% confidence intervals (CIs) using Cox proportional hazards regression. Results: During 5.4 million person-years of follow-up, 254 (216 males) incident oesophageal adenocarcinomas occurred. At each examined age, cancer risk increased linearly per unit BMI z-score, although associations were only statistically significant for ages 9–13. The HR for the age of 13 years was 1.31 (95% CI: 1.13, 1.51) per unit BMI z-score. Associations were similar in men and women and across birth cohorts. Childhood height was not related to cancer risk in men but was in women, although these analyses included just 38 female cases. HRs per unit height z-score at the age of 13 years were 1.04 (0.90, 1.19) in males and 1.77 (1.27, 2.47) in females, with similar results observed at the other examined ages. Conclusion: Individuals with higher childhood BMI were at elevated risk of oesophageal adenocarcinoma, even though these cancers occurred many decades later in life. Although the mechanisms require further investigation, our findings provide additional evidence for the long-term health risks of childhood obesity.

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.

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.

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-β-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 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.

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., What's new? High body mass index (BMI) early in life is linked to an increased risk of endometrial cancer in adulthood. Potentially influencing that association are the amount by which BMI increases in childhood, as well as the timing of BMI increase. Here, analyses of data from the Copenhagen School Health Records Register for girls ages 6 to 14 shows that endometrial cancer risk is increased by greater BMI gain across ages, while the specific age at which BMI increases occurs has little impact. Excess BMI gain at any time during childhood could set the stage for endometrial carcinogenesis.

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, p0.08). 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.

Greater attained height and greater body mass index (BMI; weight (kg)/height (m)(2)) in young adulthood have been associated with glioma risk, but few studies have investigated the association with body size at birth or during childhood, when the brain undergoes rapid cell growth and differentiation. The Copenhagen School Health Records Register includes data on 320,425 Danish schoolchildren born between 1930 and 1989, with height and weight measurements from ages 7-13 years and parentally recorded birth weights. We prospectively evaluated associations between childhood height and BMI, birth weight, and adult glioma risk. During follow-up (1968-2010), 355 men and 253 women aged ≥18 years were diagnosed with glioma. In boys, height at each age between 7 and 13 years was positively associated with glioma risk; hazard ratios per standard-deviation score at ages 7 (approximately 5.1 cm) and 13 (approximately 7.6 cm) years were 1.17 (95% confidence interval (CI): 1.05, 1.30) and 1.21 (95% CI: 1.09, 1.35), respectively. No associations were observed for childhood height in girls or for BMI. Birth weight was positively associated with risk (per 0.5 kg: hazard ratio = 1.13, 95% CI: 1.04, 1.24). These results suggest that exposures associated with higher birth weight and, in boys, greater height during childhood may contribute to the etiology of adult glioma.

The present study examined whether exposure to vitamin D from fortified margarine and milk during prenatal life influenced mean birth weight and the risk of high or low birth weight. The study was based on the Danish vitamin D fortification programme, which was a societal intervention with mandatory fortification of margarine during 1961–1985 and voluntary fortification of low-fat milk between 1972 and 1976. The influence of prenatal vitamin D exposure on birth weight was investigated among 51 883 Danish children, by comparing birth weight among individuals born during 2 years before or after the initiation and termination of vitamin D fortification programmes. In total, four sets of analyses were performed. Information on birth weight was available in the Copenhagen School Health Record Register for all school children in Copenhagen. The mean birth weight was lower among the exposed than non-exposed children during all study periods (milk initiation − 20·3 (95 % CI − 39·2, − 1·4) g; milk termination − 25·9 (95 % CI − 46·0, − 5·7) g; margarine termination − 45·7 (95 % CI − 66·6, − 24·8) g), except during the period around the initiation of margarine fortification, where exposed children were heavier than non-exposed children (margarine initiation 27·4 (95 % CI 10·8, 44·0) g). No differences in the odds of high (>4000 g) or low (

Prostate cancer is the second most common cancer among men worldwide and it is most frequent in high-income countries (World Cancer Research Fund/American Institute for Cancer Research, 2007; Globocan, 2012). Despite affecting large numbers of men, the aetiology of the disease is poorly understood. Moreover, none of the well-established risk factors such as age, ethnicity or a family history of prostate cancer are modifiable. Other prostate cancer risk factors that have been identified include adult obesity and dietary components, each of which are potentially modifiable, as well as non-modifiable risk factors such as adult height, genetic polymorphisms and hormonal factors. The contributions of these factors to the aetiology of prostate cancer are, however, unclear (Gronberg, 2003; Hsing and Chokkalingam, 2006). Adult anthropometry has been evaluated in relation to prostate cancer risk in several studies. Two meta-analyses have established that taller men have an increased risk of prostate cancer, however the effect sizes are modest (MacInnis and English, 2006;Zuccolo et al, 2008). Recently we found that tall boys, especially in late childhood, had an elevated risk of developing prostate cancer in adulthood (Cook et al, 2013). Additionally, several studies have found indications that adult obesity increases the risk of prostate cancer. However, the effect of greater adult body mass index (BMI; kg m−2) on prostate cancer risk is relatively weak (ranging in magnitude from a 3 to 6% increased risk per 5 kg m−2; MacInnis and English, 2006; Renehan et al, 2008), although the effects appear to be stronger for aggressive and fatal prostate cancers (MacInnis and English, 2006;Discacciati et al, 2011; Discacciati et al, 2012). As the growth of the prostate organ starts early in life, and the development of prostate cancer likely occurs over a long period before it manifests clinically, it is plausible that this process originates early in life (Freedland and Platz, 2007; Wilson, 2011). Consequently, childhood may represent an essential period where early exposures could affect prostate cancer risk later in life. Excess weight during childhood has various adverse consequences for long-term health (Ahlgren et al, 2004; Baker et al, 2007; Reilly and Kelly, 2011). Only a few studies have, however, investigated if childhood body size is associated with the risk of prostate cancer in adulthood, and their findings are equivocal (Andersson et al, 1995; Ilic et al, 1996; Giovannucci et al, 1997; Hsing et al, 2000; Dal et al, 2004; Jeffreys et al, 2004; Robinson et al, 2005; Barba et al, 2008). The only cohort study using measured heights and weights did not find an effect of childhood BMI, but this study was limited by a low number of prostate cancer cases as well as a wide age range of the included boys (Jeffreys et al, 2004). The remaining studies relied on a mid-life recall of childhood weight (Andersson et al, 1995; Ilic et al, 1996) or body size (Giovannucci et al, 1997; Hsing et al, 2000; Dal et al, 2004; Robinson et al, 2005; Barba et al, 2008), which might have resulted in exposure misclassification bias that usually results in attenuation of effects towards the null. We investigated whether a larger BMI in childhood, independent of and adjusted for height, as well as longitudinal changes in BMI during childhood were associated with an increased risk of prostate cancer in adulthood in a large Danish population-based cohort of men. In addition, to examine whether changes in diagnostic procedures over time and the stage of the cancer affected these associations, we conducted additional analyses exploring the effects of the introduction of prostate-specific antigen (PSA) testing and the Tumour, Node, Metastasis (TNM) stage of the neoplasm.

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.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.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/mChildhood 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.

Background: Adult height has been positively associated with prostate cancer risk. However, the exposure window of importance is currently unknown and assessments of height during earlier growth periods are scarce. In addition, the association between birth weight and prostate cancer remains undetermined. We assessed these relationships in a cohort of the Copenhagen School Health Records Register (CSHRR). Methods: The CSHRR comprises 372,636 school children. For boys born between the 1930s and 1969, birth weight and annual childhood heights—measured between ages 7 and 13 years—were analyzed in relation to prostate cancer risk. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI). Results: There were 125,211 males for analysis, 2,987 of who were subsequently diagnosed with prostate cancer during 2.57 million person-years of follow-up. Height z-score was significantly associated with prostate cancer risk at all ages (HRs, 1.13 to 1.14). Height at age 13 years was more important than height change (P = 0.024) and height at age 7 years (P = 0.024), when estimates from mutually adjusted models were compared. Adjustment of birth weight did not alter the estimates. Birth weight was not associated with prostate cancer risk. Conclusions: The association between childhood height and prostate cancer risk was driven by height at age 13 years. Impact: Our findings implicate late childhood, adolescence, and adulthood growth periods as containing the exposure window(s) of interest that underlies the association between height and prostate cancer. The causal factor may not be singular given the complexity of both human growth and carcinogenesis. Cancer Epidemiol Biomarkers Prev; 22(12); 2232–40. ©2013 AACR.

Background: Based on animal studies, n-3 polyunsaturated fatty acids (PUFAs) have been suggested to lower the risk of obesity and inflammation. We aimed to investigate if, among humans, intake of n-3 PUFAs was associated with i) total body fat, ii) body fat distribution and iii) obesity-related inflammatory markers. Methods: The study population consisted of 1,212 healthy individuals with information on habitual food intake from food frequency questionnaires, six different measures of body fat, and levels of six circulating inflammatory markers. Multiple linear regression analysis of intakes of PUFAs in relation to outcomes were performed and adjusted for potential confounders. Results: Absolute n-3 PUFA intake, but not n-3/n-6, was inversely associated with the different measures of body fat. Among n-3 PUFA derivatives, only α-linolenic acid (ALA) was inversely associated with body fat measures. No significant interactions with the dietary macronutrient composition were observed. Pro-inflammatory cytokines were not associated with absolute PUFA intake, but the macrophage inflammatory protein-1α (MIP-1α) was associated with the n-3/n-6 ratio. Conclusion: In humans, intake of n-3 PUFAs, in particular ALA, is beneficially associated with body fatness. The favourable association is, however, not reflected in systemic levels of pro-inflammatory cytokines, nor is it influenced by macronutrients in the diet.

SummaryWhat is already known about this subject The risk of childhood obesity is influenced by a number of pre- and post-natal factors. The risk of childhood obesity is correlated with body weight during infancy, which might be related to the psychomotor development of the child. The previous literature on motor milestones and childhood overweight is limited and results are inconsistent. What this study adds Weight status in early life and timing of achievement of gross motor milestones (the ability to sit and walk) are largely independent of each other. Timing of achievement of motor milestones in early life does not predict overweight or increased BMI later in childhood. Background Overweight may hinder achievement of gross motor milestones and delayed achievement of milestones may increase the risk of later overweight for reasons involving physical activity and the building of lean body mass. Objective To investigate whether increased birth weight and body mass index (BMI) at 5 months is associated with the achievement of the ability to sit up and walk and whether delayed achievement of these milestones is associated with overweight at age 7 years. Methods We used data from the Danish National Birth Cohort on 25 148 children born between 1998 and 2003. Follow-up took place from 2003 to 2010. Mean age at follow-up was 7.04 years. We used logistic and linear regression analyses. Results Birth weight and BMI at 5 months were marginally associated with earlier achievement of the ability to sit up and walk (regression coefficients between −0.027 months; [CI −0.042; −0.013] and −0.092 months [CI −0.118; −0.066]). Age in months of sitting and walking were not associated with overweight at age 7 years (ORs between 0.97 [CI 0.95–1.00] and 1.00 [CI 0.96–1.04]). Later achievement of sitting and walking predicted lower BMI at age 7 years (ln-BMI –z-scores between −0.023 [CI −0.029; −0.017] and −0.005 [CI −0.015; 0.005)). Conclusions All observed associations were of negligible magnitude and we conclude that birth weight or BMI at age 5 months and motor milestones appear largely independent of each other and that timing of achievement of motor milestones seems not to be associated with later overweight or increased BMI.

Childhood obesity and related co-morbidities are increasing. This intervention study assessed the associations between weight changes and lipidemia in obese children and adolescents.A total of 240 obese children and adolescents (median age, 11.3 years; range, 3.9-20.9) were enrolled in a best-practice multidisciplinary chronic care treatment program. The concentrations of total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglycerides (TGs) and anthropometric data comprising height and weight were collected at baseline and after up to 39 months of continuous treatment.The BMI standard deviation score (SDS) decreased in 51% of patients and maintained unchanged in 32% of patients during the treatment. At baseline, 65 (27.1%) of the patients exhibited dyslipidemia defined as increased concentrations of total cholesterol (200 mg/dL), LDL (130 mg/dL), or TGs (150 mg/dL), or decreased HDL concentration (35 mg/dL). Dyslipidemia improved with weight loss; the odds ratio (OR) was 0.37 per BMI SDS (p = 0.014) after adjusting for age, sex, and baseline BMI SDS. Baseline TG concentration correlated positively and HDL concentration correlated negatively with baseline BMI SDS. Weight loss was associated with a decrease in the concentrations of total cholesterol (p = 0.0005), LDL (p0.0001), non-HDL (p0.0001), and TGs (p0.0001), and with an increase in HDL concentration (p0.0001).High lipid concentrations were associated with childhood obesity. The lipid profile improved during weight loss independently of the baseline BMI SDS and baseline lipid concentration.

BACKGROUND: Heavy children have an increased risk of being overweight young adults. Whether this risk remains in late adulthood is not fully elucidated. We investigated body mass index (BMI; kg/m(2)) tracking from childhood to late adulthood.METHODS: From the Copenhagen School Health Records Register, 72 959 men and 25 252 women born 1930-1989 with BMI values at 7 and/or 13 years and as adults were included. Using a meta-regression approach, age- and sex-specific partial correlation analyses and logistic regressions were performed.RESULTS: Correlations between BMI at 7 years and young adult ages (18-19 years) were r=0.55 for men and r=0.55 for women. At late ages (60-69 years) these were r=0.28 for men and r=0.26 for women. The correlations did not differ by birth years. Compared with normal-weight 7-year-olds, overweight children had a higher odds of overweight at 18-19 years; odds ratio (OR)=14.02 (95% confidence interval [CI]:12.14-16.19) for men and 10.46 (95% CI:4.82-22.70) for women. At ages 60-69 years ORs were 5.46 (95% CI:0.95-31.36) for men and 1.61 (95% CI:0.83-3.15) for women. Correlations and ORs were stronger at age 13 years than pre-pubertal age 7 years, but the overall patterns were similar.CONCLUSIONS: BMI tracking was weaker at late adult ages than young ages. Although BMI tracks across the life course, childhood BMI is relatively poor at identifying later adult overweight or obesity at ages when chronic diseases generally emerge.International Journal of Obesity accepted article preview online, 11 May 2016. doi:10.1038/ijo.2016.88.

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.

Highlights • High birth weight is associated with an increased risk of adult colon cancer. • High birth weight is associated with a decreased risk of adult rectal cancer. • Colon and rectal cancer should investigated as two separate entities in investigations of the early life origins of disease as they may arise through different biological mechanisms., 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 3.5 kg. Above 3.5 kg an inverse association was observed (at 4.5 kg, 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 3.5 kg. The results underline the importance of investigating colon and rectal cancer as two different entities.

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.

What is already known about this subject • Investigations of non-alcoholic fatty liver disease (NAFLD) by non-invasive imaging procedures have limited evidence. • Thirty percent of obese children are estimated to have NAFLD and implications for future morbidity are uncertain. What this study adds • Many obese children and youths exhibit a high liver fat content as examined by magnetic resonance spectroscopy. • Associations between liver fat content, anthropometry, abdominal adipose tissue distribution and liver enzymes are illustrated. Summary The study aims to investigate the degree of hepatic steatosis and associations with the amount of abdominal subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), anthropometric data and biochemical measures of liver enzymes in children and youths included in obesity treatment. The study included 164 patients, aged 6–20 years, with a body mass index (BMI) above the 90th percentile for sex and age. Liver fat content was measured by magnetic resonance spectroscopy (MRS). SAT and VAT were measured by magnetic resonance imaging. Hepatic steatosis was defined as liver fat content >5% (steatosis-5%) and 9% (steatosis-9%), respectively. Data on waist circumference (WC) and blood samples were available in 124 patients. Steatosis-5% and steatosis-9% were identified in 45% and 27% of the patients, respectively. These patients had increased SAT, VAT, BMI standard deviation score, WC/height ratio, alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) levels. GGT, ALT and VAT were found to be independent risk factors of hepatic steatosis. In this study, a substantial proportion of obese children and youths have hepatic steatosis. Therefore, it is important to examine these subjects for the degree of fat in their liver. Future studies focusing on hepatic steatosis should consider the use of MRS in addition to blood samples.

Background The role of environmental factors in development of inflammatory bowel disease (IBD) remains uncertain. The aim of the present study was to assess a number of formerly suggested environmental factors in a case-control study of an unselected and recently diagnosed group of patients with IBD and a control group of orthopaedic patients. Methods A total of 123 patients diagnosed with Crohn's disease (CD) and 144 with ulcerative colitis (UC) in Copenhagen (2003–2004) were matched 1:1 on age and gender to 267 orthopaedic controls. Participants received a questionnaire with 87 questions concerning environmental factors prior to IBD/orthopaedic admission. Odds ratios (OR) were calculated by logistic regression. Results Being breastfed > 6 months (OR, 0.50; 95% CI, 0.23–1.11) and undergoing tonsillectomy (OR, 0.49; 95% CI, 0.31–0.78) decreased the odds for IBD, whereas appendectomy decreased the odds for UC only (OR, 0.29; 95% CI, 0.12–0.71). Vaccination against pertussis (OR, 2.08; 95% CI, 1.07–4.03) and polio (OR, 2.38; 95% CI, 1.04–5.43) increased the odds for IBD, whereas measles infection increased the odds for UC (OR, 3.50; 95% CI, 1.15–10.6). Low consumption of fibres and high consumption of sugar were significantly associated with development of CD and UC. Smoking increased the risk for CD and protected against UC. Conclusion Among Danish patients with CD and UC belonging to an unselected cohort, disease occurrence was found to be associated both with well-known factors such as smoking and appendectomy, and with more debated factors including breastfeeding, tonsillectomy, childhood vaccinations, childhood infections, and dietary intake of fibres and sugar.

To investigate whether delivery mode (vaginal versus by caesarean section), maternal pre-pregnancy body mass index (BMI) and early exposure to antibiotics (6 months of age) influence child's risk of overweight at age 7 years, hence supporting the hypotheses that environmental factors influencing the establishment and diversity of the gut microbiota are associated with later risk of overweight.Longitudinal, prospective study with measure of exposures in infancy and follow-up at age 7 years.A total of 28 354 mother-child dyads from the Danish National Birth Cohort, with information on maternal pre-pregnancy BMI, delivery mode and antibiotic administration in infancy, were assessed. Logistic regression analyses were performed with childhood height and weight at the 7-year follow-up as outcome measures.Delivery mode was not significantly associated with childhood overweight (odds ratio (OR):1.18, 95% confidence interval (CI): 0.95-1.47). Antibiotics during the first 6 months of life led to increased risk of overweight among children of normal weight mothers (OR: 1.54, 95% CI: 1.09-2.17) and a decreased risk of overweight among children of overweight mothers (OR: 0.54, 95% CI: 0.30-0.98). The same tendency was observed among children of obese mothers (OR: 0.85, 95% CI: 0.41-1.76).The present cohort study revealed that a combination of early exposures, including delivery mode, maternal pre-pregnancy BMI and antibiotics in infancy, influences the risk of overweight in later childhood. This effect may potentially be explained by an impact on establishment and diversity of the microbiota.

Gestational weight gain (GWG) is associated with childhood obesity. We analyzed whether this effect persists into adulthood and is mediated by effects in childhood.The design of the study a prospective birth cohort study established in 1959-1961.The subjects were offspring (n = 4234 of whom 2485 had information from the last follow-up) of mothers included in 'The Copenhagen Perinatal Cohort' during pregnancy or at birth.Information on maternal pre-pregnancy body mass index (BMI), GWG and several potential confounders were collected around delivery. Information on offspring BMI was available from various follow-up examinations from 1 to 42 years of age. The association of GWG with offspring BMI was analyzed by regression models including confounders. Using path analysis, the association of GWG with adult BMI was disentangled into an association mediated through childhood BMI and one independent hereof.GWG was associated with offspring BMI at all ages. At the age of 42 years (n = 1540), there was an increasing risk of obesity (odds ratio (OR) 1.08, 95% confidence interval (CI) 1.03-1.14 per kg GWG, P = 0.003). Only half of the association of GWG on offspring adult BMI was mediated through birth weight and BMI up to 14 years of age.Greater GWG is associated with an increased BMI in childhood through adulthood and with an increased risk of obesity in adults. Only part of the association with adult BMI is mediated by childhood BMI, suggesting that excessive GWG induces a persisting susceptibility to obesogenic environments. As GWG is greater in women with small pre-pregnancy body weight, this implies a reinforcement of the obesity epidemic in the next generation. Our findings provide support for avoiding excessive GWG.

The inverse associations between birth weight and later adverse health outcomes and the positive associations between adult body size and poor health imply that increases in relative body size between birth and adulthood may be undesirable. In this paper, the authors describe life course path analysis, a method that can be used to jointly estimate associations between body sizes at different time points and associations of body sizes throughout life with health outcomes. Additionally, this method makes it possible to assess both the direct effect and the indirect effect mediated through later body size, and thereby the total effect, of size and changes in size on later outcomes. Using data on childhood body size and adult systolic blood pressure from a sample of 1,284 Danish men born between 1936 and 1970, the authors compared results from path analysis with results from 3 standard regression methods. Path analysis produced easily interpretable results, and compared with standard regression methods it produced a noteworthy gain in statistical power. The effect of change in relative body size on adult blood pressure was more pronounced after age 11 years than in earlier childhood. These results suggest that increases in body size prior to age 11 years are less harmful to adult blood pressure than increases occurring after this age.

Objective To examine if number of remaining teeth was associated with development of cardiovascular morbidity and mortality over 5–12 years. Methods Prospective observational study among 1474 men and 1458 women born 1922, 1932, 1942 or 1952 from The Danish MONICA follow up study (MONItoring trends in and determinants of CArdiovascular disease) in 1987–88 and 1993–94. Subjects were followed in Danish registers for fatal and non-fatal cardiovascular disease, coronary heart disease or stroke. Results Tooth loss was strongly associated with incidence of stroke, and to a lesser extent, incidence of cardiovascular disease and coronary heart disease, during averagely 7.5 years of follow-up. Compared to those with most teeth remaining, the edentulous suffered > 3-fold increased Hazard (HR) of developing stroke (HR = 3.25; 95% CI: 1.48–7.14), whereas the risk of developing any cardiovascular disease was increased by 50% (HR = 1.50; 95% CI: 1.02–2.19). Risk for coronary heart disease was increased by 31%, but was not significant, after the adjustment for education, age, smoking, diabetes, alcohol intake, systolic blood pressure and body mass index (HR = 1.31; 95% CI: 0.74–2.31). Associations were similar for men and women. Conclusion These findings may have implications for future prevention of cardiovascular disease in general, and of stroke in particular, because tooth loss may serve as a simple, and early means to identify high-risk individuals.

The authors investigated the shape, sex- and age-dependency, and possible confounding of the association between birth weight and systolic blood pressure (SBP) in 197,954 adults from 20 Nordic cohorts (birth years 1910-1987), one of which included 166,249 Swedish male conscripts. Random-effects meta-regression analyses were performed on estimates obtained from age- and sex-stratified analyses within each of the cohorts. There was an inverse association between birth weight and SBP, irrespective of adjustment for concurrent body mass index. The association was linear for males, but for females with a birth weight greater than 4 kg, SBP increased with birth weight (p < 0.01). The association was stronger in the older age groups (p < 0.05), although this could have been a birth cohort effect. The association was stronger among females than among males (p = 0.005) when birth weight was less than or equal to 4 kg. The estimated effect of birth weight on SBP at age 50 years was -1.52 mmHg/kg (95% confidence interval: -2.27, -0.77) in men and -2.80 mmHg/kg (95% confidence interval: -3.85, -1.76) in women. Exclusion of the Swedish conscripts produced nearly identical results. This meta-analysis supports the evidence of an inverse birth weight-SBP association, regardless of adjustment for concurrent body size. It also reveals important heterogeneity in the shape and strength of the association by sex and age.

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.