Background: Childhood body mass index (BMI) trajectories, BMI, height, and birth weight were investigated in relation to biliary tract cancer (BTC) risk in this population-based cohort study. Methods: The study included 172,113 males and 168,503 females born between 1930 and 1996 from the Copenhagen School Health Records Register. Heights and weights measured at ages 6-15 years identified five sex-specific BMI trajectories. BMI and height were analyzed as z scores; overweight was defined via US Centers for Disease Control and Prevention criteria. Sex-specific hazard ratios (HRs) were estimated via birth cohort-stratified Cox regressions. Results: During a median follow-up of 34.5 years, 635 individuals developed BTCs. Overweight (HR, 1.58; 95% confidence interval [CI], 1.06-2.34) and obesity trajectories in males (HR, 3.22; 95% CI, 1.61-6.44) and the obesity trajectory in females (HR, 2.88; 95% CI, 1.62-5.15) were associated with increased BTC risk compared with the average BMI trajectory. Childhood overweight at age 7 years was associated with increased intrahepatic bile duct cancer risk in males (HR, 2.66; 95% CI, 1.48-4.75) and extrahepatic bile duct cancer risk in females (HR, 3.83; 95% CI, 1.94-7.56). Taller childhood height was linked to a higher BTC risk in males only; birth weight showed no associations. Conclusions: Childhood overweight and obesity increase BTC risk in adulthood.

Higher body mass index (BMI) in childhood is associated with hypertension (HTN) especially in young adulthood. We examined whether longitudinal patterns of BMI development in childhood are associated with HTN across adult ages. We included 124 670 children (51% boys), born between 1960-1996, from the Copenhagen School Health Records Register with height and weight measurements at ages 6-15 years. Latent class trajectory models were used to identify five sex-specific BMI trajectories: below-average, average, above-average, overweight, and obesity. Individuals were followed from age 25 in national health registers from 1995-2022 for HTN. Cox models were used to estimate sex-specific hazard ratios (HRs) with 95% confidence intervals (CIs) for HTN across childhood BMI trajectories, with adjustment for birth cohort and parental education. Follow-up was split into ages 25-39, 40-49, and 50-62 years. Over a median 18-year follow-up, 5 970 men (9.4%) and 5 712 women (9.3%) developed HTN. Men and women with above-average, overweight, and obesity childhood BMI trajectories had higher hazards of HTN than those with the average trajectory. Associations attenuated with age but remained significant. Compared to men with the average trajectory, the obesity trajectory was associated with a HR = 4.31 (95% CI: 3.45-5.37) at ages 25-39 and HR = 2.12 (1.63-2.76) at ages 50-62 years. Compared to women with the average trajectory, the obesity trajectory was associated with a HR = 3.53 (2.89-4.30) at ages 25-39 and HR = 2.19 (1.70-2.82) at ages 50-62 years. Childhood BMI trajectories are positively associated with adult HTN in a dose-response manner highlighting the potential value of early obesity prevention.

OBJECTIVE:To investigate temporal incidence trends in endometrial intraepithelial neoplasia and endometrial cancer by histological type, age at diagnosis, and socioeconomic status in Denmark over the period 2005-2022. MAIN OUTCOME MEASURES:We identified all cases of endometrial intraepithelial neoplasia and endometrial cancer in 2005-2022, and obtained individual-level information on education, income and hysterectomies for the total Danish female population from nationwide registries. Hysterectomy-corrected age-standardized incidence rates were calculated for endometrial intraepithelial neoplasia and endometrial cancer, overall and stratified by type, age, and socioeconomic status. To summarize incidence trends over time, the annual percentage change was calculated. RESULTS:During the study period, 2560 females were diagnosed with endometrial intraepithelial neoplasia and 12,845 with endometrial cancer. The incidence of endometrial intraepithelial neoplasia was stable (range: 3.1-4.3 per 100,000 female-years) independent of age, and was most common among postmenopausal women. The overall incidence of endometrial cancer was also stable, at approximately 15 per 100,000 female-years. Among postmenopausal women, the incidence of endometrioid tumors decreased, whereas non-endometrioid tumors increased; in 2021-2022, non-endometrioid cancers accounted for 20.6% of all cases. Among females with higher socioeconomic status, the incidence of endometrioid endometrial cancer decreased. In contrast, the incidence of endometrial intraepithelial neoplasia and non-endometrioid endometrial cancer increased among females with lower socioeconomic status. CONCLUSION:The incidence of endometrial intraepithelial neoplasia and endometrial cancer overall remained stable. The incidence of endometrial cancer varied by both subtype and age. Our results suggest increasing rates of endometrial intraepithelial neoplasia and non-endometrioid tumors among females with lower socioeconomic status and a decreasing trend of endometrioid cases among the highest socioeconomic groups.

Importance:Concomitant with the global obesity epidemic, fertility has declined in Western countries with birth rates falling below replacement levels. A higher body mass index (BMI) among women is associated with reduced fertility, but associations with body size earlier in life are underexplored. Objective:To investigate whether trajectories of childhood BMI are associated with timing of first childbirth and infertility in women. Design, Setting, and Participants:This prospective, population-based cohort study used linked national register and school health examination data of women aged 18 to 45 years who were born in Copenhagen, Denmark, between 1950 and 1989. Participants were followed up for reproductive outcomes from January 1, 1977 to December 31, 2022. Analytic work was conducted from May to October 2025. Exposure:Measured height and weight data used to calculate childhood BMI trajectories from ages 6 to 15 years. Main Outcomes and Measures:Registration of childbirth and hospital-based diagnoses of infertility identified in the Medical Birth Register, the Danish Infertility Cohort, the National Patient Register, and the In Vitro Fertilization Register. Hazard ratios (HRs) and 95% CIs were estimated using Cox regression models. Results:This study included 60 864 women in the childbirth analysis, of whom 47 669 (78.3%) gave birth (median [IQR] age, 27.2 [23.7-30.9] years); 58 148 were included in the primary infertility analysis, of whom 5381 (9.3%) were diagnosed with primary infertility (median [IQR] age, 31.3 [27.9-35.1] years); and 63 066 were included in the any infertility analysis, of whom 6961 (11.0%) were diagnosed with any infertility (median [IQR] age, 31.9 [28.4-35.7] years). Women with an obesity trajectory in childhood had a lower hazard of giving birth than those with an average trajectory, and this hazard decreased with increasing age (ages 25-29 years: HR, 0.78 [95% CI, 0.72-0.86]; ages 35-45 years: HR, 0.56 [95% CI, 0.46-0.67]). Similarly, women with an overweight trajectory during childhood had a lower hazard of giving birth, which decreased with increasing age. No associations were observed between the childhood BMI trajectories and primary or any infertility. Conclusions and Relevance:In this cohort study of Danish women, associations with childbirth decreased from mid- to late-reproductive ages, when the window of fertility narrows. These findings suggest that childhood body size is associated with timing of childbirth, highlighting the importance of addressing women's reproductive health early in the life course.

Adenomyosis was first described in the mid-19th century and recognised as a separate disease entity in the mid-20th century. Nonetheless, its aetiology remains poorly understood. The disease is characterised by the presence of endometrial glands and stroma within the uterine myometrium and is most commonly associated with abnormal uterine bleeding, chronic pelvic pain and infertility. It additionally adversely impacts women's quality of life [1]. Estimates of the burden of adenomyosis vary widely across populations and depend on the diagnostic criteria used; it is substantially underdiagnosed. With estimates ranging from 1% to 70% of women, the true global prevalence is unknown [2]. In this issue of Paediatric and Perinatal Epidemiology, Hall et al. [3] investigate whether a wide range of potential intrauterine and early-life factors are associated with adenomyosis. Underpinning this investigation is a theoretical link between in utero influences on oestrogen production (through effects on the hypothalamus-pituitary-ovarian axis), contributing to adenomyosis's pathogenesis. The authors conducted a case–control study using a population of women from Washington State, USA, aged 18–59 years, at enrolment into the Keiser Permanente Healthcare System. They used a group of 386 women with adenomyosis and compared it with a group of 233 women who underwent a hysterectomy and a group of 323 women from the healthcare population. The authors examined nine early-life exposures, ranging from the mother's age and smoking status to the participant's birthweight and birth order. Due to statistical instability, however, the authors did not report associations for all of the exposures they initially intended to. Among the intriguing findings were indications of increased odds of adenomyosis with younger maternal age at birth, later birth order and maternal smoking (only among never-smoking participants). Additionally, the authors found some indications of positive associations with birthweight. However, all risk estimates had wide confidence intervals, suggesting imprecision. Two previous Scandinavian cohort studies found limited evidence for associations between early-life risk factors, including birthweight, and risks of adenomyosis [4, 5]. Even if birthweight was not associated with adenomyosis risks in the previous investigations, a study conducted within our research group found that body mass index in childhood may be a risk factor for subsequent risks of adenomyosis [5]. Hence, this emphasises that examinations of early-life factors, exceeding beyond intrauterine and perinatal life, also warrant consideration as indicators of adenomyosis risk. Among the strengths of the study by Hall et al. is the inclusion of pathology-confirmed adenomyosis by hysterectomy, which is considered the gold standard for diagnosing adenomyosis. However, as acknowledged by the authors, there is also a risk of women having undiagnosed adenomyosis among population controls, as imaging technologies were not available when the study was conducted. Another strength is that information about a range of potential confounding factors was available, and the authors performed several sensitivity analyses. Some important limitations of the case–control study by Hall et al. should be considered. The exposure information was from self-reported recall of participants (or in combination with their mothers), which may introduce potential exposure misclassification. Although early-life factors may contribute to the subsequent development of adenomyosis, the findings by Hall et al. remain open to interpretation as the confidence intervals were wide and included many possible risk values. For example, the adjusted odds ratio of later versus first-born child was 1.51 (95% confidence interval 0.88, 2.59), which is compatible with an increased odds of 51%. Although this is the most likely odds, the imprecise 95% CI suggests a wide margin of the potential odds: from 12% reduced odds (OR: 0.88) to 159% increased odds (OR: 2.59). Due to the small number of cases, the risk estimates have relatively high uncertainty, which precludes firm conclusions. Therefore, future studies should include populations of sufficient size with available and accurate information on both exposures and outcomes to be able to interpret if and how early-life factors may relate to the subsequent development of adenomyosis, preferably using cohort designs. Adenomyosis is a debilitating disease with a substantial impact on women's lives and further constitutes a high burden to health care systems. Unfortunately, this disease is understudied compared with many other benign gynaecological reproductive conditions. With advances in imaging technology, non-invasive diagnostics are now possible. As diagnoses of adenomyosis are no longer reliant on uterine specimens from hysterectomies, it is emerging that adenomyosis may occur earlier in a woman's life than previously thought. The study by Hall et al. is timely and highlights the relevance of early-life and even intergenerational investigations into the origins of adenomyosis. By identifying risk factors early in life in combination with the possibility of detecting adenomyosis at younger ages, better health outcomes for women afflicted with this debilitating disease may be ensured. The author thanks Jennifer L. Baker for her comments on an earlier draft of this commentary. The author declares no conflicts of interest. The author has nothing to report.

BACKGROUND AND AIM:Infant weight gain is positively associated with fat and lean mass later in life, but whether it relates to adult cardiovascular disease (CVD) risk factors is ambiguous. We examined associations between infant weight gain trajectories and adult CVD risk factors. METHODS AND RESULTS:We included 739 individuals from the Copenhagen Perinatal Cohort. Repeated infant weight measurements and information on adult CVD risk factors at age 48-51 years were available. Five infant weight gain trajectories were estimated using latent class modelling (very low-moderately increasing; low-markedly increasing; low-stable increasing; average-stable increasing [reference group]; high-moderately increasing). Linear regression models were adjusted for parental and infant factors and additionally for birthweight. Compared with the average-stable increasing weight gain trajectory, in men, the very low-moderately increasing trajectory was associated with higher systolic and diastolic blood pressure (DBP), triglycerides, low-density lipoprotein and total cholesterol. In women, the low-markedly increasing trajectory was associated with higher DBP and the low-stable increasing trajectory was associated with lower body mass index and body fat percentage. The high-moderately increasing trajectory was associated with higher waist circumference in men and lower total cholesterol in women. Additional adjustment for birthweight attenuated some, but not all, associations. CONCLUSION:Infant weight gain trajectories were not consistently associated with CVD risk profiles during adulthood. In men, the very-low moderately increasing weight trajectory had a worse CVD risk profile. Women with the low-stable increasing weight trajectory tended to have a better CVD risk profile.

BACKGROUND:Although lactation may reduce maternal risk of breast cancer, other potential long-term health benefits of lactation for mothers are largely unknown. OBJECTIVES:We examined whether the durations of predominant and any lactation were associated with maternal risks of coronary artery disease (CAD) and stroke. METHODS:In this prospective cohort study, we followed up 6857 mothers from the Copenhagen Perinatal Cohort who gave birth during 1959-1961 at median age 24 y (IQR, 20-30 y). Durations of predominant and any lactation were assessed at the infant's 1-y examination. Diagnoses of CAD (n = 701 at 45-70 y; n = 593 at >70 y) and stroke (n = 410 at 45-70 y; n = 535 at >70 y) were obtained from national health registers during 1977-2022. Hazard ratios (HRs) and 95% CIs were estimated by Cox regressions without and with adjustment for demographics, metabolic risk during pregnancy, pregnancy complications, and reproductive history. RESULTS:Durations of predominant and any lactation were inversely associated with risk of CAD, but not with stroke, when using lactation as a continuous variable. In categorical analyses, mothers who lactated for >4 months had 41% (HR: 0.59; 95% CI: 0.46, 0.75) and 34% (HR: 0.66; 95% CI: 0.48, 0.92) lower risk of CAD and stroke, respectively, at ages 45-70 y, compared with mothers who lactated ≤0.5 months. After adjustment for demographic, metabolic, and reproductive risk factors during pregnancy, these associations attenuated (HR: 0.78; 95% CI: 0.60, 1.01 for CAD; HR: 0.90; 95% CI: 0.64, 1.27 for stroke). No associations were observed with CAD or stroke diagnosed after age 70 y. CONCLUSIONS:Limited evidence exists for an association between lactation and maternal risk of stroke. Longer durations of lactation are associated with lower risks of maternal CAD diagnosed before age 70 y. Adjustment for risk factors attenuate the associations, which suggests these factors may partly confound the benefits of lactation on maternal risks of CAD.

Purpose Whether breast density mediates associations between early life body size and pubertal timing with postmenopausal breast cancer is underexplored. Methods We studied 33,939 Danish women attending the Capital Mammography Screening Program at ages 50-69 years. Early life anthropometry and pubertal timing information came from the Copenhagen School Health Records Register. Postmenopausal breast cancer information came from the Danish Breast Cancer Group database (n=833). Breast density (BI-RADS) was categorized as low (n=25,464; 75%) or high. Risk ratios (RR) and hazard ratios (HR) were estimated using generalized linear regression and Cox proportional hazards analyses. Counterfactual mediation analyses were conducted. Results Evidence was limited for associations between birthweight and pubertal timing with breast density or breast cancer. Childhood BMI was inversely associated with high breast density (age 13y, RR=0.77 [0.72-0.81] for a z-score of 0.6 versus 0) and breast cancer (HR=0.90 [0.83-0.96] per z-score). Breast density mediated 37% (17-170%) of this association. Although childhood height was associated with breast density and breast cancer, there were few indications of mediation by breast density. Conclusions Breast density may partially explain the inverse association between childhood BMI and postmenopausal breast cancer, but not the positive association between childhood height and postmenopausal breast cancer.

The steady rise in overweight and obesity in Europe disproportionately affects people and communities with a lower socio-economic position (SEP). Many obesity prevention approaches exist, but these have had limited reach and unsatisfactory effects thus far, especially in low-SEP populations. In this context, there is a need for implementation of effective individual-level and population-based preventive strategies that also tackle health inequalities. Effective strategies require consideration of the complex and cross-domain obesity risk factors across the life course. Feasible and acceptable strategies require multisectoral collaborations and innovative approaches, including a whole-of community and systems perspective. With the Horizon Europe-funded OBCT project, we aim to quantify the relative contribution of biological, socio-cultural and built environment factors to obesity and the interactions of these risks within and across various life course stages; and translate the resulting knowledge into practical, equitable, and effective tools for action. These tools will include: a comprehensive obesity risk screener; a map of the obesogenicity of neighbourhood environments as well as trends in obesity prevalence of each European country; recommendations for lifestyle behaviours (diet, physical activity, sedentary behaviours) to prevent obesity during key life transition stages; a decision support dashboard for policy makers; and co-developed toolboxes to support implementation of policy recommendations in low-SEP communities. OBCT's outputs will highlight the areas and domains in which obesity should be targeted and will empower the research community, policymakers, health professionals and residents in Europe to adapt and implement strategies to effectively reduce obesity risk, particularly in low-SEP communities.

OBJECTIVE:Most studies have investigated how childhood BMI impacts risks of single diseases. We investigated whether sex-specific patterns of disease diagnoses from ages 15 to 60 years differed by childhood BMI. METHODS:We included 112,952 children (55,603 girls) from the Copenhagen School Health Records Register, born 1962-1996, with measured weights and heights. BMI at 7 years was classified as underweight (4.3%), normal weight (83.1%), overweight (9.2%), or obesity (3.5%). Hospital-based diagnoses came from national registers. Sex-specific cumulative incidences were calculated for the 50 most frequent diseases per BMI group. RESULTS:Individuals with childhood obesity had the highest estimated mean number of hospital-based diagnoses by age 60, 18.2 (95% CI: 16.9-19.5) in females and 15.1 (13.8-16.4) in males. Corresponding estimates for normal weight were 14.7 (14.5-14.9) in females and 11.7 (11.5-11.8) in males. Among females and males with obesity in childhood, the most common diagnosis before age 60 years was adult overweight/obesity (36.4% and 11.8%, respectively). There were only minor differences for other diseases by childhood BMI categories. CONCLUSIONS:Adults with obesity in childhood had the highest number of hospital-based diagnoses. Disease patterns across the life course were generally similar by childhood BMI groups apart from adult overweight and obesity.

BACKGROUND:It is increasingly recognized that early life factors play a role in the rising prevalence of cancer in young adult life. Acute childhood infections may protect against development of cancer, but evidence is limited. We investigated whether infection-related hospital contacts during the first 24 months of life were associated with the risk of cancer in early-mid adult life in a large population-based Danish cohort. METHODS:We included 68,538 individuals (33,569; 49.0 % women) born 1977-1996 from the Copenhagen School Health Records Register. Using individual-level linkage to national registries, we obtained information on infection-related hospital contacts between birth and 24 months and early-onset cancer (diagnosed 15-45 years). Hazard ratios (HR) and 95 % confidence intervals (CI) were estimated using Cox regressions adjusted for maternal education. RESULTS:From birth to 24 months of life, 14,718 individuals (21.5 %) had at least one infection-related hospital contact. During follow-up, 788 individuals were diagnosed with cancer. Compared to individuals who did not have an infection-related hospital contact, those who had a least one had a lower risk of early-mid adulthood cancer (HR=0.82, 95 % CI: 0.68-0.98). We found limited evidence of a dose-response inverse effect of infection-related hospital contacts on cancer risk. CONCLUSION:Infection-related hospital contacts during the first 24 months of life was associated with a reduced risk of cancer in early-mid adult life. Replication in other populations is warranted and mechanistic studies are needed to understand the biological mechanisms underlying these epidemiological observations.

Childhood adiposity markers can be standardised for height in the form of indices (marker/heightp) to make meaningful comparisons of adiposity patterns within and between individuals of differing heights. The optimal value of p has been shown to differ by birth year, sex, age, and ethnicity. We investigated whether height powers for childhood weight and fat mass (FM) differed by birth year, sex, or age over the period before and during the child obesity epidemic in Copenhagen. Population-based cross-sectional study of 391,801 schoolchildren aged 7 years, 10 years and 13 years, born between 1930 and 1996, from the Copenhagen School Health Records Register. Sex- and age-specific estimates of the height powers for weight and FM were obtained using log–log regression, stratified by a decade of birth. For weight, amongst children born 1930–39, optimal height powers at 7 years were 2.20 (95

BACKGROUND:Being breastfed has established benefits for infant health, but its long-term effects on adult diseases, including cancer, remain underexplored. We examined associations between being breastfed in infancy and the risks of common cancers. METHODS:Data from 339,115 participants (191,117 women) enrolled in the UK Biobank with self-reported breastfeeding data were linked to national cancer registries. Cox models estimated sex-specific hazard ratios (HR) and 95% confidence intervals (CI) for the associations between being breastfed (ever/never) and risks of overall cancer as well as common cancer sites. RESULTS:In total, 34,392 incident cancers (17,895 in women) were registered. The HR of overall cancer associated with being breastfed was 1.05 (95% CI 1.01-1.09) in women and 1.00 (95% CI 0.96-1-04) in men. In site-specific analysis being breastfed was associated with an increased risk of breast and ovarian cancer in women and a reduced risk of oesophageal cancer in men. DISCUSSION:We found that having been breastfed was associated with a marginally increased risk of adult cancer in women, but we found no evidence of an association in men. These findings should be viewed within the study limitations, and do not outweigh the many benefits that breastfeeding provides.

BackgroundThe early life factors of birthweight, child weight, height, body mass index (BMI) and pubertal timing are associated with risks of breast cancer. However, the predictive value of these factors in relation to breast cancer is largely unknown. Therefore, using a machine learning approach, we examined whether birthweight, childhood weights, heights, BMIs, and pubertal timing individually and in combination were predictive of breast cancer.MethodsWe used information on birthweight, childhood height and weight, and pubertal timing assessed by the onset of the growth spurt (OGS) from 164,216 girls born 1930-1996 from the Copenhagen School Health Records Register. Of these, 10,002 women were diagnosed with breast cancer during 1977-2019 according to a nationwide breast cancer database. We developed a feed-forward neural network, which was trained and tested on early life body size measures individually and in various combinations. Evaluation metrics were examined to identify the best performing model.ResultsThe highest area under the receiver operating curve (AUC) was achieved in a model that included birthweight, childhood heights, weights and age at OGS (AUC = 0.600). A model based on childhood heights and weights had a comparable AUC value (AUC = 0.598), whereas a model including only childhood heights had the lowest AUC value (AUC = 0.572). The sensitivity of the models ranged from 0.698 to 0.760 while the precision ranged from 0.071 to 0.076.ConclusionWe found that the best performing network was based on birthweight, childhood weights, heights and age at OGS as the input features. Nonetheless, this performance was only slightly better than the model including childhood heights and weights. Further, although the performance of our networks was relatively low, it was similar to those from previous studies including well-established risk factors. As such, our results suggest that childhood body size may add additional value to breast cancer prediction models.

AIM:To examine trends in all body mass index (BMI) groups in children from 1936 to 2011. METHODS:We included 197 694 girls and 201 276 boys from the Copenhagen School Health Records Register, born between 1930 and 1996, with longitudinal weight and height measurements (6-14 years). Using International Obesity Task Force criteria, BMI was classified as underweight, normal-weight, overweight and obesity. Sex- and age-specific prevalences were calculated. RESULTS:From the 1930s, the prevalence of underweight was stable until a small increase occurred from 1950 to 1970s, and thereafter it declined into the early 2000s. Using 7-year-olds as an example, underweight changed from 10% to 7% in girls and from 9% to 6% in boys during the study period. The prevalence of overweight plateaued from 1950 to 1970s and then steeply increased from 1970s onwards and in 1990-2000s 15% girls and 11% boys at 7 years had overweight. The prevalence of obesity particularly increased from 1980s onwards and in 1990-2000s 5% girls and 4% boys at 7 years had obesity. These trends slightly differed by age. CONCLUSION:Among Danish schoolchildren, the prevalence of underweight was greater than overweight until the 1980s and greater than obesity throughout the period. Thus, monitoring the prevalence of childhood underweight remains an important public health issue.

Background: Associations between a high body mass index (BMI) at single timepoints during child-and adulthood and risks of post-menopausal breast cancer are well-established, but associations with BMI across the lifecourse remains largely unknown. Therefore, we examined whether lifecourse BMI trajectories were associated with risks of post-menopausal breast cancer overall and by estrogen receptor (ER) status.Methods: We included 6698 Danish women born 1930-1946. Information on BMI at ages 6-15 years came from the Copenhagen School Health Records Register, and information on BMI at ages 20, 30, 40, 50 and/or 50-64 years came from the Diet, Cancer and Health cohort. Breast cancer cases (n = 577) were identified in the Danish Breast Cancer Cooperative Group database. Six BMI trajectories were identified using latent class trajectory modelling. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox regression models.Results: Compared to women with a trajectory characterized by an average BMI gain across life, women with the two trajectories with steep increases in BMI during childhood and adolescence that thereafter largely stabilized, had lower risks of post-menopausal breast cancer and ER-positive tumors. The adjusted HRs for ER-positive tumors were 0.67 (95% CI: 0.47-0.95) and 0.68 (95% CI: 0.46-1.01), respectively. In contrast, women with a trajectory with a low gain in BMI during childhood and adolescence followed by a subsequent steep increase during adulthood, had higher risks of post-menopausal breast cancer and ER-positive tumors when compared to women with an average BMI gain. The adjusted HR for ER-positive tumors was 1.28 (95% CI: 0.98-1.67).Conclusions: Our findings suggest that the timing of excess gain in BMI across the lifecourse impacts subsequent post-menopausal breast cancer risks. Thus, the BMI development across life is likely useful in the identification of women at increased risks of post-menopausal breast cancer.

Background Elevated childhood body mass index (BMI), commonly examined as a "once-only" value, increases the risk of cancer and type 2 diabetes (T2D) in adulthood. Continuous exposure to adiposity during childhood may further increase cancer risk. We examined whether longitudinal childhood BMI trajectories were associated with adult obesity-related cancer and the role of adult-onset T2D in these associations. Methods Five sex-specific latent class BMI trajectories were generated for 301 927 children (149 325 girls) aged 6-15 years from the Copenhagen School Health Records Register. Information on obesity-related cancers and T2D was obtained from national health registers. Incidence rate ratios (IRR), cumulative incidences, and confidence intervals (CI) were estimated using Poisson regressions. Results Compared with the average childhood BMI trajectory (containing approximately 40% of individuals), the rate of obesity-related cancer (excluding breast cancer) increased with higher childhood BMI trajectories among women. The highest rates occurred in the overweight (IRR = 1.27, 95% CI = 1.17 to 1.38) and obesity (IRR = 1.79, 95% CI = 1.53 to 2.08) BMI trajectories. Similar patterns were observed among men. In contrast, women with the obesity childhood BMI trajectory had the lowest rate of pre- and postmenopausal breast cancer (IRR = 0.59, 95% CI = 0.43 to 0.80, and IRR = 0.41, 95% CI = 0.30 to 0.57, respectively). For all trajectories, the cumulative risk of obesity-related cancer increased with adult-onset T2D. Conclusion Consistent childhood overweight or obesity may increase the rates of adult obesity-related cancer and decrease the rates of breast cancer. Adult-onset T2D conferred additional risk for obesity-related cancer, but the effect did not differ across childhood BMI trajectories.

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 - 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.

AIMS:We examined associations between five body mass index (BMI) trajectories from ages 6-15 years and register-based adult-onset type 2 diabetes mellitus (T2D) and coronary heart disease (CHD) with and without adjustment for adult BMI. METHODS:Child and adult BMI came from two Danish cohorts and 13,205 and 13,438 individuals were included in T2D and CHD analyses, respectively. Trajectories were estimated by latent class modelling. Incidence rate ratios (IRRs) were estimated with Poisson regression. RESULTS:In models without adult BMI, compared to the lowest trajectory, among men the T2D IRRs were 0.92 (95 %CI:0.77-1.09) for the second lowest trajectory and 1.51 (95 %CI:0.71-3.20) for the highest trajectory. The corresponding IRRs in women were 0.92 (95 %CI:0.74-1.16) and 3.58 (95 %CI:2.30-5.57). In models including adult BMI, compared to the lowest trajectory, T2D IRRs in men were 0.57 (95 %CI:0.47-0.68) for the second lowest trajectory and 0.26 (95 %CI:0.12-0.56) for the highest trajectory. The corresponding IRRs in women were 0.60 (95 %CI:0.48-0.75) and 0.59 (95 %CI:0.36-0.96). The associations were similar in direction, but not statistically significant, for CHD. CONCLUSIONS:Incidence rates of adult-onset T2D were greater for a high child BMI trajectory than a low child BMI trajectory, but not in models that included adult BMI.