Publications by authors named "Julie Aarestrup"

22 Publications

  • Page 1 of 1

Birthweight, Childhood Body Mass Index, Height and Growth, and Risk of Polycystic Ovary Syndrome.

Obes Facts 2021 12;14(3):283-290. Epub 2021 May 12.

Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, The Capital Region, Frederiksberg, Denmark.

Introduction: Adult obesity is linked with polycystic ovary syndrome (PCOS), but the importance of body size at ages before PCOS is diagnosed is unknown.

Objective: To investigate associations between a woman's own birthweight, childhood body mass index (BMI), height and growth patterns in relation to her risk of PCOS.

Methods: We included 65,665 girls from the Copenhagen School Health Records Register, born in the period 1960-1996, with information on birthweight and measured weight and height at the ages of 7-13 years. Overweight was defined using International Obesity Task Force (IOTF) criteria. From the Danish National Patient Register, 606 women aged 15-50 years were identified. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by Cox regression analysis.

Results: Birthweight was not associated with PCOS. At the age of 7-13 years, girls with overweight had a higher risk of developing PCOS than girls without overweight; HR 2.83 (95% CI 2.34-3.42) at age 7 years and 2.99 (95% CI 2.38-3.76) at age 13 years. Furthermore, girls with overweight at both 7 and 13 years had a higher risk of developing PCOS than girls without overweight or overweight at only one age. Height was positively associated with PCOS risk at all ages. Girls who were persistently tall or changed from tall to average height had a higher risk of developing PCOS than girls with average height growth.

Conclusion: Overweight and tall stature in childhood are positively associated with PCOS risk, but birthweight is not.
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http://dx.doi.org/10.1159/000515294DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8255636PMC
November 2021

Association of Childhood Fat Mass and Weight With Adult-Onset Type 2 Diabetes in Denmark.

JAMA Netw Open 2021 04 1;4(4):e218524. Epub 2021 Apr 1.

Population Health Research Institute, St George's, University of London, Cranmer Terrace, London, United Kingdom.

Importance: Childhood obesity, defined by cutoffs based on the weight-based marker of body mass index, is associated with adult type 2 diabetes (T2D) risk. Whether childhood fat mass (FM) is the driver of these associations is currently unknown.

Objective: To quantify and compare height-independent associations between childhood FM and weight with adult T2D risk in a historic Danish cohort.

Design, Setting, And Participants: This population-based retrospective cohort study included schoolchildren from The Copenhagen School Health Records Register born between January 1930 and December 1985 with follow-up to adulthood through December 31, 2015. Analyses were based on 269 913 schoolchildren aged 10 years with 21 896 established adult T2D cases and 261 192 children aged 13 years with 21 530 established adult T2D cases for whom childhood height and weight measurements, as well as predicted FM, were available. Statistical analyses were performed between April 2019 to August 2020.

Exposures: Childhood FM and weight at ages 10 and 13 years.

Main Outcomes And Measures: Diagnoses of T2D were established by linkage to national disease registers for adults aged at least 30 years. Sex-specific Cox regression quantified associations, adjusted for childhood height, which were evaluated within 5 birth-cohort groups. Group-specific results were pooled using random-effects meta-analyses accounting for heterogeneity across group-specific associations.

Results: This cohort study analyzed data from 269 913 children aged 10 years (135 940 boys [50.4%]) with 21 896 established adult T2D cases and 261 192 children aged 13 years (131 025 boys [50.2%]) with 21 530 established adult T2D cases. After adjusting for childhood height, increases in FM and weight (per kilogram) among boys aged 10 years were associated with elevated T2D risks at age 50 years of 12% (hazard ratio [HR], 1.12; 95% CI, 1.10-1.14) and 7% (HR, 1.07; 95% CI, 1.05-1.09), respectively, and among girls aged 10 years of 15% (HR, 1.15; 95% CI, 1.13-1.17) and 10% (HR, 1.10; 95% CI, 1.08-1.11), respectively. Among children aged 13 years, increases in FM and weight (per kilogram) were associated with increased T2D risks at age 50 years of 10% (HR, 1.10; 95% CI, 1.09-1.10) and 6% (HR, 1.06; 95% CI, 1.05-1.07) for boys, respectively, and of 10% (HR, 1.10; 95% CI, 1.10-1.11) and 7% (HR, 1.07; 95% CI, 1.06-1.08), respectively, for girls.

Conclusions And Relevance: This cohort study found that a 1-kg increase in childhood FM was more strongly associated with increased adult T2D risk than a 1-kg increase in weight, independent of childhood height. Information on FM, rather than weight-based measures, focuses on a modifiable component of weight that may be associated with adult T2D risk. These findings support the assessment of childhood FM in adiposity surveillance initiatives in an effort to reduce long-term T2D risk.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.8524DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087954PMC
April 2021

Associations between body mass index trajectories in childhood and cardiovascular risk factors in adulthood.

Atherosclerosis 2020 12 9;314:10-17. Epub 2020 Oct 9.

Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, The Capital Region, Copenhagen, Denmark; Novo Nordisk Foundation Center for Basic Metabolic Research, Human Genomics and Metagenomics in Metabolism, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Electronic address:

Background And Aims: Children with a growth trajectory of overweight have higher levels of cardiovascular disease (CVD) risk factors than children with a normal-weight trajectory. However, less is known about how trajectories of body mass index (BMI) across the rest of the BMI spectrum relate to CVD risk factors and whether adult BMI affects these associations. Our aim was to examine associations between childhood BMI trajectories and adult CVD risk factors.

Methods: We included 2466 individuals with childhood weights and heights (ages 6-14) from the Copenhagen School Health Records Register and adult CVD risk factors (ages 20-81) from the Copenhagen City Heart Study. Associations between childhood BMI trajectories identified by latent class modelling and CVD risk factors were examined using generalized linear regression analyses with and without adjustment for adult BMI. Normal-weight and overweight were defined by growth references from the Centers for Disease Control and Prevention.

Results: We identified four childhood trajectories within the normal-weight spectrum and one trajectory of overweight. Compared to the trajectory with the lowest BMI level, several higher BMI trajectories were associated with worse circumference, HDL and glucose homeostasis in adulthood. The highest trajectory was additionally associated with higher total cholesterol and triglycerides. When adjusting for adult BMI, the higher BMI trajectories had lower waist circumference, blood pressure and triglycerides.

Conclusions: Trajectories of BMI within the normal-weight range and in the overweight range are associated with a worse CVD risk profile than in the lowest BMI trajectory, and these associations are modifiable by growth after childhood.
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http://dx.doi.org/10.1016/j.atherosclerosis.2020.10.011DOI Listing
December 2020

Early life body size and its associations with adult bladder cancer.

Ann Hum Biol 2020 Mar;47(2):166-172

Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, The Capital Region, Frederiksberg, Denmark.

Adult overweight is a potential bladder cancer (BC) risk factor, but little is known about size earlier in life. To investigate if birth weight, childhood body mass index (BMI), height and growth are associated with adult BC. Anthropometric information from birth and ages 7-13 on 315,763 individuals born 1930-1989 in the Copenhagen School Health Records Register was linked to national registers. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated by Cox regression. 1145 individuals (839 men) were diagnosed with BC. Sex differences were not detected. Childhood BMI had positive associations and height had inverse associations with BC; at age 13, HR = 1.10 (95% CI: 1.02-1.18) per BMI z-score and HR = 0.94 (95% CI: 0.89-1.00) per height z-score. A pattern of above-average increases in BMI from 7 to 13 years had higher hazards of BC than average increases. Above-average growth in height was not significantly associated with BC. Compared with birth weights of 3.5 kg, low (2.5 kg) and high (4.5 kg) values were associated with increased hazards of BC; HR = 1.26 (95% CI: 1.01-1.58) and HR = 1.36 (95% CI: 1.09-1.70), respectively. A high BMI, a short height, excess BMI gain in childhood and low and high birth weights are associated with increased hazards of BC.
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http://dx.doi.org/10.1080/03014460.2019.1707873DOI Listing
March 2020

Association of Birth Weight, Childhood Body Mass Index, and Height With Risk of Hidradenitis Suppurativa.

JAMA Dermatol 2020 07;156(7):746-753

Department of Dermato-Venereology & Wound Healing Centre, Bispebjerg Hospital, Copenhagen, Denmark.

Importance: There is a lack of evidence on the association of birth weight, childhood body mass index (BMI), change in BMI during childhood, and childhood height with subsequent risks of hidradenitis suppurativa (HS) in adulthood.

Objective: To investigate the association of birth weight, childhood BMI, change in BMI during childhood, and childhood height with subsequent risks of HS in adulthood in a large Danish population-based cohort.

Design, Setting, And Participants: This cohort study included 347 200 schoolchildren from the Copenhagen School Health Records Register born from 1930 to 1996 who were linked to the Danish National Patient Register of hospital discharge diagnoses to identify cases of HS. Birth weight was reported by parents or guardians, whereas childhood weight and height were measured by school physicians or nurses at ages 7 through 13 years. Cox proportional hazards regressions were used to estimate hazard ratios (HRs) and 95% CIs. Statistical analysis was performed from February 20, 2019, to May 15, 2019.

Main Outcomes And Measures: A diagnosis of HS as recorded in the Danish National Patient Register.

Results: Among the 347 200 children included in the study (175 750 boys) during the follow-up period from 1977 to 2017, 1037 individuals (677 females; median age at diagnosis, 39 years [range, 15-73 years]) received a diagnosis of HS. A nonlinear (U-shaped) association was found between birth weight and HS, such that both the lightest (2.00-2.75 kg; HR, 1.36 [95% CI, 1.10-1.68]) and the heaviest babies (4.26-5.50 kg; HR, 1.39 [95% CI, 1.01-1.93]) had increased risks of HS compared with normal-weight babies (3.26-3.75 kg; P = .04 for deviation from linearity). The risk of HS increased significantly with increasing BMI z score at each age from 7 to 13 years, from an HR of 1.32 (95% CI, 1.24-1.40) per BMI z score at 7 years of age to an HR of 1.50 (95% CI, 1.40-1.61) per BMI z score at 13 years of age. Compared with children with a normal weight at 7 and 13 years of age, those with a normal weight at 7 years of age and overweight at 13 years of age had a significantly increased risk of HS (HR, 2.11 [95% CI, 1.63-2.74]) and children with persistent overweight at both ages also had an increased risk of HS (HR, 2.61 [95% CI, 2.02-3.38]). Children with overweight at 7 years of age but with normal weight at 13 years of age did not have a significantly increased risk of HS (HR, 1.05 [95% CI, 0.67-1.67]). Childhood height at all ages was not associated with risk of HS (children at 7 years had an HR of 1.00 [95% CI, 0.94-1.07], and those 13 years had an HR of 1.06 [95% CI, 0.99-1.13], per z score).

Conclusions And Relevance: This cohort study found that both the lightest and heaviest babies had increased risks of HS. Childhood BMI was positively and significantly associated with risk of HS development in adulthood. These findings suggest that returning to normal weight before puberty reduces risks of HS to levels observed in children who were never overweight. Childhood height was not associated with risk of HS.
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http://dx.doi.org/10.1001/jamadermatol.2020.1047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7191432PMC
July 2020

Birth weight, childhood body mass index and height and risks of endometriosis and adenomyosis.

Ann Hum Biol 2020 Mar 9;47(2):173-180. Epub 2020 Mar 9.

Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, The Capital Region, Copenhagen, Denmark.

Body size in adult life is likely associated with risks of endometriosis and adenomyosis, yet little is known about associations with body size earlier in life. To examine whether birth weight, childhood body mass index (BMI) and height are associated with risks of endometriosis and adenomyosis. From the Copenhagen School Health Records Register, 171,447 girls born 1930-1996, with measured weights and heights at ages 7-13 were included. Outcomes were obtained from health registers. Cox regressions were performed to estimate hazard ratios (HR) and 95% confidence intervals (CI). During follow-up, 2149 endometriosis cases and 1410 adenomyosis cases were diagnosed. Childhood BMI was inversely associated with endometriosis (HR = 0.92 [95% CI: 0.88-0.96] per -score at age 7). In contrast, childhood height was positively associated with endometriosis (HR = 1.09 [95% CI: 1.05-1.14] per -score at age 7). Associations with childhood body size did not differ by endometriosis location. Childhood BMI and height had limited associations with adenomyosis. Birth weight was not associated with endometriosis or adenomyosis. Lean and tall girls are more often diagnosed with endometriosis, but not adenomyosis. These findings suggest that indicators of endometriosis risk are already apparent at early ages.
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http://dx.doi.org/10.1080/03014460.2020.1727011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905846PMC
March 2020

Early life body size, growth and risks of systemic lupus erythematosus - A large Danish observational cohort study.

Semin Arthritis Rheum 2020 12 4;50(6):1507-1512. Epub 2020 Feb 4.

Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, The Capital Region, Copenhagen, Denmark; Novo Nordisk Foundation Center for Basic Metabolic Research, Human Genomics and Metagenomics in Metabolism, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark. Electronic address:

Objectives: Adult obesity may increase the risks of systemic lupus erythematosus (SLE), and there are genetic links between adult height and SLE. Thus, it is plausible that size earlier in life may be important in the aetiology of SLE as well. We investigated whether birthweight, childhood body mass index (BMI; [kg/m]), height and growth are associated with risks of adult SLE.

Methods: The study included 346,627 children from the Copenhagen School Health Records Register, born 1930-1996 with measured weights and heights from 7-13 years. Birthweight information was available from 1936. Linkages were made to the Danish National Patient Register for information on registrations of SLE. During follow-up, 435 individuals (366 women) were registered with SLE. Cox proportional hazards regressions were performed to estimate hazard ratios (HR) and 95% confidence intervals (CI).

Results: No differences by sex were detected in any of the associations. Birthweight was not associated with SLE risks. Childhood BMI and height were positively and linearly associated with SLE risks. For BMI at age 7, the HR was 1.11 (95% CI: 1.01-1.23) per z-score. For height at age 7, the HR was 1.13 (95% CI: 1.02-1.24) per z-score. The estimates were similar in magnitude across all childhood ages for BMI and height. There were limited indications that change in BMI or growth in height during childhood influence the risks of SLE in adulthood.

Conclusions: Childhood body size is associated with risks of adult SLE, which supports the hypothesis that early life factors are important in SLE aetiology.
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http://dx.doi.org/10.1016/j.semarthrit.2020.01.011DOI Listing
December 2020

Birthweight, childhood overweight, height and growth and adult cancer risks: a review of studies using the Copenhagen School Health Records Register.

Int J Obes (Lond) 2020 07 23;44(7):1546-1560. Epub 2020 Jan 23.

Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, The Capital Region, Copenhagen, Denmark.

Background: Most identified risk factors for cancer primarily occur in adulthood. As cancers generally have long latency periods, it is possible that risk factors acting earlier in life and accumulation of risks across the life course are important. Thus, focusing only on adult overweight as a modifiable risk factor may overlook childhood as an important aetiologic time window when body size is relevant for future cancer risks. The objective of this study was to review the evidence for associations between birthweight, body mass index (BMI), height and growth from 7-13 years and adult cancer risks based on studies using the Copenhagen School Health Records Register.

Methods: The register contains measured anthropometric information on 372,636 children born in 1930-1989. All studies examining associations between early life body size and risks of adult cancer (until 85 years, diagnosed in 1968-2015) were included, comprising 31 studies on 16 different cancer sites. Cancer diagnoses were retrieved via individual-level linkages to the Danish Cancer Registry.

Results: Birthweight was differentially associated with bladder, breast, colon, glioma, Hodgkin's disease, liver, kidney (renal cell), melanoma, ovarian, rectal, testicular and thyroid cancer. BMI in childhood was positively associated with risks of bladder (only late childhood), colon, endometrial, kidney, liver, oesophageal (only late childhood), ovarian, pancreatic (<70 years), prostate (only before childhood height adjustment) and thyroid cancer, whereas it was inversely associated with breast cancer. Child height was positively associated with breast, colon, endometrial, glioma, Hodgkin's disease, kidney, melanoma, oesophageal (only women), ovarian, prostate, testicular and thyroid cancer and inversely associated with bladder cancer. Greater than average increases in childhood BMI or linear growth at ages 7-13 increased risks of several cancers.

Conclusions: Early life body size and growth are associated with many, but not all adult cancers, suggesting that the aetiology of several cancers may lie earlier in life than previously thought.
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http://dx.doi.org/10.1038/s41366-020-0523-9DOI Listing
July 2020

Changes and correlations in height from 7 to 69 years of age across the birth years of 1930 to 1989.

Am J Hum Biol 2020 07 26;32(4):e23378. Epub 2019 Dec 26.

Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, The Capital Region, Copenhagen, Denmark.

Objectives: The aims of this study were to describe changes in height during childhood and to investigate potential changes in the proportion of children attaining final height in childhood and in correlations between child and adult height across birth cohorts.

Methods: We included 363 059 children (179 906 girls) from the Copenhagen School Health Records Register, who were born between 1930 and 1989, with height measurements at ages 7, 10, or 13 years. Linkages to data resources containing adult height values between ages 18 and 69 years were possible for a subpopulation of 96 133 individuals (23 051 women). Birth years were categorized as 1930 to 1939, 1940 to 1949, and 1950 to 1989. Descriptive height statistics were estimated by birth years and birth cohorts. Height correlations were examined using sex- and age-specific partial Pearson correlation analyses and meta-regression techniques.

Results: Across 60 birth years, mean child heights at age 7 increased by 2.9 cm in girls and 3.0 cm in boys, and adult heights increased as well. The proportions of children attaining final height by age 13 remained low across the birth cohorts; nonetheless, there was a significant increase from 0.7% to 1.5% in girls only (P < .0001). Both child-child and child-adult height correlations were strong and remained relatively stable across birth cohorts.

Conclusions: Mean child and adult height increased during the study period, but the proportion of children attaining final height at age 13 remained low. Child-child and child-adult height correlations were largely unchanged across birth cohorts.
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http://dx.doi.org/10.1002/ajhb.23378DOI Listing
July 2020

Birthweight and risk of thyroid cancer and its histological types: A large cohort study.

Cancer Epidemiol 2019 10 17;62:101564. Epub 2019 Jul 17.

Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, The Capital Region, Nordre Fasanvej 57, 2000, Frederiksberg, Denmark; Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, University of Copenhagen, Blegdamsvej 3B, 2200, Copenhagen, Denmark. Electronic address:

Background: The aetiology of thyroid cancer is poorly understood, but it is possible that this malignancy has origins early in life. It is, however, currently unknown if birthweight, as an indicator of prenatal growth, is related to thyroid cancer risk.

Objective: To investigate if birthweight is associated with the later risk of thyroid cancer and its histological types.

Methods: 246,141 children (120,505 girls, 125,636 boys) from the Copenhagen School Health Records Register, born 1936-1989, were prospectively followed in the Danish Cancer Registry. Cox regressions were used to estimate hazards ratios (HR) and 95% confidence intervals (CI).

Results: During follow up, 241 individuals (172 women, 69 men) were diagnosed with thyroid cancer (162 papillary, 53 follicular). Birthweight was significantly and positively associated with risk of thyroid cancer overall (HR = 1.30 [95% CI: 1.03-1.64] per kilogram). There were no sex differences in the associations. Birthweight was positively and significantly associated with follicular thyroid cancer (HR = 1.74 [95% CI: 1.07-2.82] per kilogram), and although there was an indication of a positive association, it did not reach statistical significance for the more common papillary type (HR = 1.20 [95% CI: 0.90-1.59] per kilogram).

Conclusion: A heavier weight at birth is associated with an elevated risk of total and follicular thyroid cancer, which underscores that prenatal exposures may be important in thyroid cancer aetiology.
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http://dx.doi.org/10.1016/j.canep.2019.07.003DOI Listing
October 2019

Cardiovascular Risk Profile Among Patients With Inflammatory Bowel Disease: A Population-based Study of More Than 100 000 Individuals.

J Crohns Colitis 2019 Mar;13(3):319-323

Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, The Capital Region, Copenhagen, Denmark.

Background And Aims: Patients with inflammatory bowel disease have increased risks of cardiovascular diseases, but the role of traditional and non-traditional cardiovascular risk factors remains unclear. We investigated if the cardiovascular risk profile differs between patients with inflammatory bowel disease and individuals in the general population.

Methods: We included a population of 108789 participants from the Copenhagen General Population Study of individuals of Danish descent aged 20-100 years. The population included 1203 individuals with prevalent inflammatory bowel disease [347 with Crohn's disease and 856 with ulcerative colitis]. The cardiovascular risk profile was assessed by traditional risk factors [plasma lipids and glucose, body composition measures, and blood pressure] and non-traditional risk factors [inflammatory markers and biomarkers of liver and pancreas function].

Results: Even though patients with inflammatory bowel disease more frequently are diagnosed with cardiovascular diseases, traditional cardiovascular risk factors were not increased. Indeed, patients with inflammatory bowel disease had slightly lower plasma levels of total cholesterol and low-density lipoprotein cholesterol. Levels of inflammatory markers, particularly high-sensitivity C-reactive protein, were higher in individuals with versus without a diagnosis of inflammatory bowel disease, when assessed at a random point in time during the disease course.

Conclusions: The increased risk of cardiovascular diseases in patients with inflammatory bowel disease may be linked to chronic systemic inflammation rather than to traditional cardiovascular risk factors. Further studies need to examine whether cardiovascular-preventive strategies should focus on optimising management of inflammation in patients with inflammatory bowel disease rather than focusing on traditional cardiovascular risk factors.
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http://dx.doi.org/10.1093/ecco-jcc/jjy164DOI Listing
March 2019

Childhood Overweight, Tallness, and Growth Increase Risks of Ovarian Cancer.

Cancer Epidemiol Biomarkers Prev 2019 01 27;28(1):183-188. Epub 2018 Sep 27.

Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, The Capital Region, Denmark.

Background: Adult body size is related to ovarian cancer risks, but size in childhood may also influence risks. We investigated if childhood body mass index (kg/m), height, and growth patterns were associated with ovarian cancer overall and by histologic subtypes, including effects of birthweight.

Methods: A cohort of 155,958 girls from the Copenhagen School Health Records Register, born 1930 to 1989 with measured weights and heights from 7 to 13 years, were included. During follow-up, 1,041 ovarian cancers were recorded. Overweight was defined using International Obesity Task Force criteria. Cox regressions were performed.

Results: Compared with non-overweight girls, at most ages girls with overweight had increased risks of ovarian cancer overall (HR range: 1.24-1.34), mucinous, endometrioid, and clear cell ovarian cancers, but not serous and other ovarian cancers. Childhood height had positive and significant associations with ovarian cancer overall (HR range: 1.07-1.10 per -score) and the endometrioid subtype but not with the other subtypes. Adjusting for birthweight minimally altered the associations with childhood body size. In growth analyses, girls with overweight or who were tall at 7 and 13 years had increased risks of ovarian cancer overall compared with average-sized girls at both ages.

Conclusions: Ovarian carcinogenesis is linked to childhood overweight, tallness, and growth, with variations across histological subtypes, suggesting that early life plays a role in the origins of this disease.

Impact: These findings emphasize that healthy body size and growth during childhood are important as they may contribute to reducing ovarian cancer risks.
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http://dx.doi.org/10.1158/1055-9965.EPI-18-0024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6325003PMC
January 2019

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

Int J Cancer 2018 08 26;143(4):767-772. Epub 2018 Mar 26.

Department of Clinical Epidemiology, Bispebjerg and Frederiksberg Hospital, The Capital Region, Copenhagen, Denmark.

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.
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http://dx.doi.org/10.1002/ijc.31354DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6041140PMC
August 2018

Birth weight and the risk of histological subtypes of ovarian and endometrial cancers: Results from the Copenhagen School Health Records Register.

Gynecol Oncol 2018 03 11;148(3):547-552. Epub 2018 Jan 11.

Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, The Capital Region, Copenhagen, Denmark; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Electronic address:

Background: Studies of birth weight associations with ovarian and endometrial cancer risks are limited with inconsistent results, and none has evaluated associations by histologic subtype. We utilized prospectively collected birth weight information to investigate the association with risk of ovarian and endometrial cancers overall and by histologic subtype.

Methods: 162,559 girls, born from 1930 to 1989, from the Copenhagen School Health Records Register (CSHRR) were followed prospectively via linkage with the Danish health registers. Ovarian (n=666) and endometrial (n=694) cancers were identified from 1978 to 2014. Cox regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI).

Results: Women with lower (2.0-3.25 vs. 3.26-3.75kg) and higher (3.75-5.5 vs. 3.26-3.75kg) birth weights had increased risks of ovarian cancer overall [HR (95% CI): 1.27 (1.06-1.52); 1.51 (1.21-1.87), respectively] and serous ovarian cancers [1.54 (1.19-1.98); 1.98 (1.47-2.67), respectively]. A decreased risk of Type II endometrial tumors was suggested per kilogram increase in birth weight [HR (95% CI): 0.63 (0.40-1.00)].

Conclusions: Our results suggest that both lower and higher birth weights were associated with increased ovarian cancer risk and associations were particularly strong for serous ovarian cancer, the most common subtype. Birth weight was not associated with most types of endometrial cancer.
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http://dx.doi.org/10.1016/j.ygyno.2017.12.031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5829014PMC
March 2018

Childhood body mass index growth trajectories and endometrial cancer risk.

Int J Cancer 2017 Jan 26;140(2):310-315. Epub 2016 Oct 26.

Institute of Preventive Medicine, Bispebjerg and Frederiksberg Hospital, The Capital Region, Copenhagen, Denmark.

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.
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http://dx.doi.org/10.1002/ijc.30464DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5132154PMC
January 2017

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

Obes Facts 2016 30;9(4):284-95. Epub 2016 Aug 30.

Institute of Preventive Medicine, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark.

Background: The stabilization in levels of childhood overweight has masked increasing gaps among different ethnic and socioeconomic groups in several countries.

Objective: To examine if levels and trends in childhood overweight and obesity differed by ethnicity and socioeconomic areas in Copenhagen schoolchildren.

Methods: From measured heights and weights of 32,951 children 5-8 and 14-16 years of age, the prevalence of overweight (including obesity) and obesity were estimated using International Obesity Task Force criteria. Differences in prevalence levels and trends across six school years by ethnicity and socioeconomic areas were examined using logistic regression.

Results: The prevalence of overweight significantly decreased from 2002 to 2007 among the youngest Western girls and boys, showed no significant changes among the oldest non-Western girls and increased among the oldest non-Western boys. In all years, the youngest non-Western children had significantly higher levels of overweight than Western children. Although the prevalence of overweight tended to be higher in low socioeconomic areas as compared with high socioeconomic areas, few differences were statistically significant. Consistent trends in overweight across the years by socioeconomic area were not observed.

Conclusion: Ethnic and social inequalities exist in childhood overweight among Copenhagen schoolchildren; thus appropriate interventions targeting high-risk groups are needed.
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http://dx.doi.org/10.1159/000446482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5644825PMC
September 2017

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

Cancer Causes Control 2016 Apr 7;27(4):561-7. Epub 2016 Mar 7.

Institute of Preventive Medicine, Bispebjerg and Frederiksberg Hospital, The Capital Region, Nordre Fasanvej 57, Hovedvejen, 2000, Frederiksberg, Denmark.

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.
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http://dx.doi.org/10.1007/s10552-016-0731-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4796358PMC
April 2016

Childhood height and birth weight in relation to future prostate cancer risk: a cohort study based on the copenhagen school health records register.

Cancer Epidemiol Biomarkers Prev 2013 Dec 2;22(12):2232-40. Epub 2013 Oct 2.

Authors' Affiliations: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, Maryland; Institute of Preventive Medicine, Bispebjerg and Frederiksberg Hospital, The Capital Region; and The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

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.
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http://dx.doi.org/10.1158/1055-9965.EPI-13-0712DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3863763PMC
December 2013

Whole grain, dietary fiber, and incidence of endometrial cancer in a Danish cohort study.

Nutr Cancer 2012 ;64(8):1160-8

Danish Cancer Society Research Center, Copenhagen, Denmark.

Whole grains and dietary fiber might be inversely associated with endometrial cancer risk through their effects on sex hormone metabolism and body fat. We investigated whether a higher intake of whole grains and dietary fiber was associated with a lower incidence of endometrial cancer in the Diet, Cancer and Health cohort of 29,875 women aged 50-64 years at enrollment in 1993-1997. Information on diet and lifestyle was derived from self-administered questionnaires. The incidence rate ratios and 95% confidence intervals were estimated based on a Cox proportional hazards model. Of the 24,418 women included as cohort members, 217 had a diagnosis of endometrial cancer. No clear associations were found between intake of whole grains or dietary fiber and the incidence of endometrial cancer.
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http://dx.doi.org/10.1080/01635581.2012.723786DOI Listing
May 2013

Plasma enterolactone and incidence of endometrial cancer in a case-cohort study of Danish women.

Br J Nutr 2013 Jun 31;109(12):2269-75. Epub 2012 Oct 31.

Danish Cancer Society Research Center, Strandboulevarden 49, DK-2100 Copenhagen Ø, Denmark.

The phyto-oestrogen enterolactone has been hypothesised to protect against hormone-dependent cancers, probably through its antioestrogenic potential. We investigated whether a higher level of plasma enterolactone was associated with a lower incidence of endometrial cancer in a case-cohort study in the ‘Diet, Cancer and Health’ cohort. The cohort study included 29 875 women aged 50–64 years enrolled between 1993 and 1997. Information on diet and lifestyle was provided by self-administrated questionnaires and blood was drawn from each participant. Time-resolved fluoroimmunoassay was used for biochemical determination of plasma enterolactone. A total of 173 cases and 149 randomly selected cohort members were included. We estimated incidence rate ratio (IRR) and 95% CI by a Cox proportional hazards model. A 20 nmol/l higher plasma concentration of enterolactone was associated with a non-significant lower risk of endometrial cancer (IRR 0.93, 95% CI 0.84, 1.04). When excluding women with low enterolactone concentrations (quartile 1) due to potential recent antibiotic use, the association became slightly stronger, but remained non-significant (IRR 0.90, 95% CI 0.79, 1.02). Menopausal status, hormone replacement therapy or BMI did not modify the association. In conclusion, we found some support for a possible inverse association between plasma enterolactone concentration and endometrial cancer incidence.
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http://dx.doi.org/10.1017/S0007114512004424DOI Listing
June 2013

Serum estrogen and SHBG levels and breast cancer incidence among users and never users of hormone replacement therapy.

Cancer Causes Control 2012 Oct 28;23(10):1711-20. Epub 2012 Aug 28.

Danish Cancer Society Research Center, Strandboulevarden 49, 2100 Copenhagen Ø, Denmark.

Objective: Levels of endogenous estrogen and SHBG are associated with risk of breast cancer among women who have never used hormone replacement therapy (HRT). We investigated these associations in both never and baseline users of HRT.

Methods: A nested case-control study was conducted within the prospective Danish population-based 'Diet, Cancer, and Health' cohort. During follow-up, 348 eligible cases were identified among 20,861 postmenopausal women and matched to 348 controls. Baseline serum samples were analyzed for estradiol, bioavailable estradiol, estrone, estrone sulfate, and SHBG. Conditional logistic regression yielded incidence rate ratios and 95 % confidence intervals for exposures analyzed continuously and categorically in models adjusted for potential confounders.

Results: Modest direct associations were identified between estrogen levels and breast cancer incidence among both never and baseline HRT users. Estrone and estrone sulfate were more consistently associated among both groups than estradiol. No association was found with SHBG.

Conclusion: Despite different hormonal profiles, higher serum estrogen levels were associated with a higher risk of breast cancer among both never and baseline HRT users. More studies are needed to support the findings for HRT users and to further investigate estrogen levels in relation to estrogen receptor-specific breast cancer and other histological and molecular subtypes.
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http://dx.doi.org/10.1007/s10552-012-0050-7DOI Listing
October 2012

Flaxseed dietary fibers lower cholesterol and increase fecal fat excretion, but magnitude of effect depend on food type.

Nutr Metab (Lond) 2012 Feb 3;9. Epub 2012 Feb 3.

Department of Human Nutrition, Faculty of Life Sciences, University of Copenhagen, Denmark.

Background: Dietary fibers have been proposed to play a role in cardiovascular risk as well as body weight management. Flaxseeds are a good source of dietary fibers, and a large proportion of these are water-soluble viscous fibers.

Method: Here, we examine the effect of flaxseed dietary fibers in different food matrices on blood lipids and fecal excretion of fat and energy in a double-blind randomized crossover study with 17 subjects. Three different 7-d diets were tested: a low-fiber control diet (Control), a diet with flaxseed fiber drink (3/day) (Flax drink), and a diet with flaxseed fiber bread (3/day) (Flax bread). Total fat and energy excretion was measured in feces, blood samples were collected before and after each period, and appetite sensation registered 3 times daily before main meals.

Results: Compared to control, Flax drink lowered fasting total-cholesterol and LDL-cholesterol by 12 and 15%, respectively, (p < 0.01), whereas Flax bread only produced a reduction of 7 and 9%, respectively (p < 0.05). Fecal fat and energy excretion increased by 50 and 23% with Flax drink consumption compared to control (p < 0.05), but only fecal fat excretion was increased with Flax bread compared to control (p < 0.05).

Conclusion: Both Flax drink and Flax bread resulted in decreased plasma total and LDL-cholesterol and increased fat excretion, but the food matrix and/or processing may be of importance. Viscous flaxseed dietary fibers may be a useful tool for lowering blood cholesterol and potentially play a role in energy balance.

Trial Registration: ClinicalTrials.gov: NCT00953004.
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http://dx.doi.org/10.1186/1743-7075-9-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3307491PMC
February 2012
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