Pediatric health service utilization at tertiary hospitals in Denmark 2000-2018.

Pediatric health service differs between and within countries. To prioritize limited resources, data-driven studies on pediatric tertiary hospital contacts are warranted. This population-based register study identified all contacts with four Danish tertiary hospitals 2000-2018 by 0-17-year-old patients. During 2000-2018, 2,496,001 individuals resided in Denmark while 0-17 years old, and the study described 829,562 inpatient and 3,932,744 outpatient contacts at tertiary hospitals by hospital, sex, age, diagnosis, department, and residence. Male patients accounted for more contacts overall (inpatient 55.51%, outpatient 52.40%) and more contacts with severe chronic disease (inpatient 56.24%, outpatient 54.41%). Median (interquartile range) patient age was 3.09 (0.26-9.96) and 8.48 (2.78-13.70) years for in- and outpatient contacts. Overall, 28.23% and 21.02% of in- and outpatient contacts included a diagnosis of a severe chronic disease, but the proportions differed across hospitals. A pattern of pediatric healthcare directed towards less severe diseases was observed: While the total number of outpatient visits at tertiary hospitals increased from 2000 to 2018, the proportion of these contacts which had a diagnosis of a severe chronic disease decreased. Future comparisons between hospitals regarding pediatric outcomes should consider potential differences in terms of uptake and diagnosis severity. Such findings may have implications for future pediatric organization, nationally and internationally.

Long-term cause-specific mortality in adolescent and young adult Hodgkin lymphoma patients treated with contemporary regimens-A nationwide Danish cohort study.

The documented treatment-induced excess mortality in Hodgkin lymphoma (HL) has spurred important treatment changes over recent decades. This study aimed to examine mortality among young HL patients treated with contemporary strategies, including historical data comparison. This nationwide study included 1348 HL patients, diagnosed in 1995-2015 and aged 15-40 at diagnosis. Among the patients, 66.5% had Ann Arbor stage I-II and 33.5% had stage III-IV disease. With a median follow-up of 14.76 years, 139 deaths occurred, yielding a 5-year overall survival of 94.6%. Older age, advanced disease, earlier treatment periods and extensive regimens were associated with higher overall mortality risk. The cumulative risk of HL-related death showed an initial sharp rise, with a plateau at 5.3% 10-year post-diagnosis. Deaths due to cardiovascular or pulmonary diseases and second cancers initially had minimal risk, gradually reaching 1.2% and 2.0% at the 20-year mark respectively. HL cases had a 7.5-fold higher mortality hazard than the background population. This study suggests that contemporary HL treatment still poses excess mortality risk, but recent changes have notably reduced overall and cause-specific mortality compared to earlier eras. Balancing treatment efficacy and toxicity remains crucial, but our findings highlight improved outcomes with modern treatment approaches.

Long-term risk of glaucoma after cataract surgery in childhood.

PURPOSE: To examine the long-term risk of glaucoma after cataract surgery in childhood. METHODS: This study took place from January 2022 until December 2022 and included patients from a large family with hereditary childhood cataract who had cataract surgery before 18 years of age. Patients underwent an ophthalmologic examination to determine the presence of glaucoma or ocular hypertension (OHT). Patients who did not want to participate in the examination could contribute with a medical journal from their treating ophthalmologist. The risk of long-term glaucoma was determined using survival analysis, and risk factors were assessed using a Cox proportional hazards regression model. RESULTS: We included 68 patients (133 eyes) with a median age at cataract surgery of 7 years (IQR: 5-10). The median follow-up time after cataract surgery to glaucoma/OHT or the latest ophthalmologic examination was 35 years (IQR: 15-48). Twelve patients (18 eyes) had glaucoma, and five patients (eight eyes) had OHT, resulting in 15 patients with glaucoma/OHT. The long-term risk of glaucoma/OHT diagnosed in adulthood was 47.7% (CI: 21.8-70.9) at the age of 70 years of patients who were free of glaucoma before their 18th year. We could not confirm or dismiss an association between glaucoma/OHT and sex, age at surgery, number of ocular interventions before 18 years of age or glaucoma after cataract surgery in a first-degree relative. CONCLUSION: Cataract surgery in childhood is associated with a high risk of late-onset glaucoma. Regular lifelong follow-up is important to ensure early diagnosis and prevent extensive vision loss.

Reduced susceptibility to COVID-19 associated with ABO blood group and pre-existing anti-A and anti-B antibodies.

BACKGROUND: Susceptibility to severe acute respiratory syndrome coronavirus 2 shows individual variability in un-vaccinated and previously un-exposed individuals. We investigated the impact of ABO blood group, titers of anti-A and anti-B, other blood group antigens, and the extracellular deposition of ABH antigens as controlled by secretor fucosyltransferase 2 (FUT2) status. STUDY DESIGN AND METHODS: We studied incidents in three different hospitals between April to September 2020, where un-diagnosed coronavirus disease 2019 (COVID-19) patients were cared for by health care workers without use of personal protection and with close contact while delivering therapy. We recruited 108 exposed staff, of whom 34 were diagnosed with COVID-19. ABO blood type, titer of anti-A and -B, blood group specific alleles, and secretor status were determined. RESULTS: Blood group O was associated with lower risk of COVID-19 (OR 0.39, 95 %CI (0.16-0.92), p = 0.03) compared to non-O, i.e., blood groups A, B and AB. High titer anti-A immunoglobulin G (IgG) compared to low titer was associated with lower risk of COVID-19 (OR 0.24 95 %CI (0.07-0.78), p = 0.017). High titer of anti-B immunoglobulin M (IgM) compared to no anti-B (IgM) was associated with lower risk of COVID-19 (OR 0.16, 95 %CI (0.039-0.608), p = 0.006) and the same applies to low titer anti-B (IgM) compared to no titer (OR 0.23, 95 %CI (0.07-0.72), p = 0.012). The 33Pro variant in Integrin beta-3, that is part of human platelet antigen 1b (HPA-1b), was associated with lower risk of COVID-19 (OR 0.23, 95 %CI (0.034-0.86), p = 0.028). CONCLUSION: Our data showed that blood group O, anti-A (IgG) titer, anti-B (IgM) titer as well as HPA-1b are associated with lower risk for COVID-19.

Fully constrained acetabular liner vs. dual mobility hip joint in the surgical treatment of metastatic bone disease of the hip: study protocol for a randomized, open-label, two-arm, non-inferiority trial evaluating the post-operative hip dislocation rate.

BACKGROUND: Patients receiving total hip arthroplasty (THA) due to metastatic bone disease of the hip (MBD) are at an increased risk of post-operative joint dislocation compared to other populations. Different joint solutions have been developed with the purpose of reducing the dislocation risk compared to regular THAs. One of these solutions, the constrained liner (CL), has been used increasingly at our department in recent years. This design, however, is prone to polyethylene wear and higher revision rates. An alternative is the dual mobility cup (DM), which has been shown to reduce the risk of dislocation in other high-risk populations. Few studies have investigated DM for THA due to MBD, and no studies have directly compared these two treatments in this population. We therefore decided to conduct a trial to investigate whether DM is non-inferior to CL regarding the post-operative joint dislocation risk in patients receiving THA due to MBD. MATERIALS AND METHODS: This study is a single-center, randomized, open-label, two-arm, non-inferiority trial. We will include 146 patients with MBD of the hip who are planned for THA at the Department of Orthopedic Surgery, Rigshospitalet. Patients with previous osteosynthesis or endoprosthetic surgery of the afflicted hip, or who are planned to receive partial pelvic reconstruction or total femoral replacement, will be excluded. Patients will be stratified by whether subtrochanteric bone resection will be performed and allocated to either CL or DM in a 1:1 ratio. The primary outcome is the 6 months post-operative joint dislocation rate. Secondary outcomes include overall survival, implant survival, the rate of other surgical- and post-operative complications, and quality of life and functional outcome scores. DISCUSSION: This study is designed to investigate whether DM is non-inferior to CL regarding the risk of post-operative dislocation in patients receiving THA due to MBD. To our knowledge, this trial is the first of its kind. Knowledge gained from this trial will help guide surgeons in choosing a joint solution that minimizes the risk of dislocation and, ultimately, reduces the need for repeat surgeries in this patient population. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05461313. Registered on July 15 2022. This trial is reported according to the items in the WHO Trial Registration Data Set (Version 1.3.1).

Estimation of time-specific intervention effects on continuously distributed time-to-event outcomes by targeted maximum likelihood estimation.

This work considers targeted maximum likelihood estimation (TMLE) of treatment effects on absolute risk and survival probabilities in classical time-to-event settings characterized by right-censoring and competing risks. TMLE is a general methodology combining flexible ensemble learning and semiparametric efficiency theory in a two-step procedure for substitution estimation of causal parameters. We specialize and extend the continuous-time TMLE methods for competing risks settings, proposing a targeting algorithm that iteratively updates cause-specific hazards to solve the efficient influence curve equation for the target parameter. As part of the work, we further detail and implement the recently proposed highly adaptive lasso estimator for continuous-time conditional hazards with L1 -penalized Poisson regression. The resulting estimation procedure benefits from relying solely on very mild nonparametric restrictions on the statistical model, thus providing a novel tool for machine-learning-based semiparametric causal inference for continuous-time time-to-event data. We apply the methods to a publicly available dataset on follicular cell lymphoma where subjects are followed over time until disease relapse or death without relapse. The data display important time-varying effects that can be captured by the highly adaptive lasso. In our simulations that are designed to imitate the data, we compare our methods to a similar approach based on random survival forests and to the discrete-time TMLE.

Pretransplant serum levels of endothelial cell activation markers are associated with graft loss and mortality after kidney transplantation.

Long-term allograft survival remains a challenge in kidney transplantation. In this study, we aimed to identify biomarkers for potentially modifiable pathways involved in the outcome of kidney transplantation. We tested the hypothesis that a pre-existing systemic environment with endothelial cell activation in the recipient is associated with the outcome after kidney transplantation. In a retrospective study cohort of 611 kidney transplanted patients, we investigated associations between serum levels of soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) before transplantation and delayed graft function, acute rejection, graft loss and mortality after transplantation. We adjusted associations for age, sex, preformed donor-specific antibodies (DSA), pretransplant diabetes, cardiovascular disease and dialysis. Additionally, we investigated if associations between endothelial cell activation markers and outcomes differed in recipients with and without preformed DSA. Serum levels of endothelial cell activation markers were associated with delayed graft function and mortality but not with rejection. Additionally, high levels of sICAM-1 were associated with graft loss. Associations were most pronounced in recipients without DSA, adjusted for potential confounders. Data suggest that endothelial cell activation at the time of transplantation is associated with graft loss and mortality after kidney transplantation, especially in transplant candidates without preformed DSA.

Mortality among patients treated for aneurysmal subarachnoid hemorrhage in Eastern Denmark 2017-2019.

OBJECTIVE: The aim of the study was to investigate (1) the 30-day, 3-month, and 12-month cumulative mortalities for patients who underwent aneurysm occlusion, and (2) the causes of death, and (3) the potential risk factors for death. METHODS: All patients who underwent surgical clipping or endovascular treatment of a ruptured aneurysm at Copenhagen University Hospital, during the period of January 1, 2017-December 31, 2019, were included and followed up for 12 months. Data regarding vital status, causes of death, comorbidities, treatment, and clinical presentations on admission was collected. The absolute mortality risk was estimated as a function of time with a 95% confidence interval. The associations between potential risk factors and death were estimated as odds ratios with 95% confidence intervals using logistic regression models. RESULTS: A total of 317 patients were included. The overall cumulative mortalities after 30 days, 3 months, and 12 months were 10.7%, 12.9%, and 16.1%, respectively. The most common cause of death was severe primary hemorrhage (52.9%), followed by infections (15.7%) and rebleeding (11.8%). WFNS score > 3 and Fisher score > 3 on admission, preprocedural hydrocephalus, and preprocedural rebleeding were found significantly associated with higher risk of death. CONCLUSIONS: Considerable mortality was seen. Possible preventable causes accounted for approximately 22% of the deaths. The occurrence of both pre- and postprocedural rebleeding's indicates an opportunity of further improvement of the mortality by (1) further reduction of time from aSAH to aneurysm occlusion and (2) continuous efforts in improving methods of aneurysm occlusion.

Employment, health visits, mental health, and mortality in parents with a chronically ill child: a Danish nationwide population-based cohort study.

Chronic diseases in children can impact their parents; this may be overlooked in a clinical setting. Our aim was to investigate associations of chronic diseases in children with their parents' employment, health care utilization, mental health, and mortality. In a matched cohort study using nationwide and population-based data in Denmark, we included parents to children (< 18 years) with acute disseminated encephalomyelitis, multiple sclerosis, type 1 diabetes, inflammatory bowel disease, and rheumatoid arthritis/juvenile idiopathic arthritis during 2008-2015. The reference group was parents to unaffected children. Outcomes were parental employment (early retirement, cash benefits, income), health care utilization (e.g., general practitioner, or hospital visits), mental health (visits to psychiatry/psychology clinics, antidepressant drug redemptions), and mortality. We included 13,769 parents with a chronically ill child and 138,606 control parents. Annual income was unaffected for two-parent families after the child's disease onset, but two-parent families had increased hazard of early retirement of 25% (95% CI = 1.01-1.54; p = 0.04). Parents with a chronically ill child had (a) increased rate of antidepressant drug redemptions or psychology/psychiatry visits (hazard ratio 1.37; 95% CI = 1.28-1.46 at 1-year follow-up); (b) increased health care utilization, with an increased marginal mean in primary care of 1% (95% CI = 1.00-1.02; p = 0.005), hospital-affiliated visits of 19% (95% CI = 1.14-1.24; p < 0.0001), and hospital admissions of 14% (95% CI = 1.09-1.20; p < 0.0001); and (c) 69% increased mortality hazard (95% CI = 1.30-2.18; p < 0.0001) in parents younger than 50 years with no comorbidities, albeit small in absolute numbers. CONCLUSION: Pediatric chronic diseases were negatively associated with parental employment, mental health, and mortality, and increased health care utilization. WHAT IS KNOWN: • Studies on the impact of pediatric chronic diseases on parental health are qualitative. • Knowledge is unavailable regarding the impact on parental work, health care utilization, and mortality. WHAT IS NEW: • Among 13,769 parents with a chronically ill child and 138,606 control parents, parents with a chronically ill child had 37% increased antidepressant drug redemptions, and these parents <50 years without comorbidities had 69% increased mortality hazard. • Medical doctors should consider the parental health condition and societal challenges related to having child with a chronic disease.

The Danish SoL Project: Effects of a Multi-Component Community-Based Health Promotion Intervention on Prevention of Overweight among 3-8-Year-Old Children.

The aim of the study was to determine the effects of a multi-component community-based health promotion intervention on body mass index (BMI) z-scores and waist circumference (WC) in three- to eight-year-old children. A quasi-experimental design was adopted to evaluate the effects of the SoL intervention involving three intervention and three control communities. The 19-month intervention was based on the supersetting approach and was designed to promote healthier eating and physical activity among children and their families. BMI z-scores and WC were measured at baseline and follow-up. At baseline, 238 (54%) and 214 (51%) of all eligible children were measured from intervention and control, respectively. The change over time in the BMI z-scores of children from the intervention group was significantly different from that of the control group (p = 0.001). BMI z-scores increased over time in the intervention group in contrast to the control group, whose BMI z-scores decreased (difference in change between groups 0.19 z-scores 95% CI 0.08, 0.30). No significant differences were observed for WC. The results showed no favourable effects of the intervention of Project SoL on BMI z-scores and WC in children. Further studies based on a larger sample size and a longer intervention duration are needed.

The HLA-DR4-DQ8 phenotype of the recipient is associated with increased mortality after kidney transplantation.

The importance of the human leukocyte antigen (HLA) system in kidney transplantation is well-known, but it remains unexplored if patient HLA antigens constitute independent risk factors in complications after transplantation. We hypothesized that specific HLA class II phenotypes associated with immune-mediated disease (HLA-IMD) predispose to immunological activity and/or complications after kidney transplantation. Based on the literature we defined HLA-DR2-DQ6; -DR3-DQ2 and -DR4-DQ8 as HLA-IMD phenotypes. We investigated associations between HLA-IMD phenotypes in patients, biomarkers of systemic chronic inflammation at the time of transplantation, and the outcome after kidney transplantation in a retrospective cohort study of 611 kidney transplanted patients. The HLA-IMD phenotypes were associated with higher levels of biomarkers of systemic inflammation. The HLA-DR4-DQ8 phenotype was associated with mortality after transplantation in Cox analyses with adjustments for confounders. Data support the hypothesis that specific HLA class II phenotypes affects immunological pathways that determine the midterm clinical outcome of kidney transplantation.

Chronic ocular graft-versus-host disease after allogeneic haematopoietic stem cell transplantation in Denmark - factors associated with risks and rates in adults according to conditioning regimen.

We investigated risks and hazard rates of developing chronic ocular graft-versus-host disease (oGVHD) in a large nationwide, single centre study by using the criteria proposed by "The International Chronic oGVHD Consensus Group". This retrospective study included 1407 consecutive adults who underwent allogeneic haematopoietic stem cell transplantation (HSCT). Patients were examined by an ophthalmologist according to the hospital's guidelines: baseline examination before HSCT, annually up to 5 years after HSCT. The 186 (13%) had dry eye disease before HSCT. The 5-year cumulative incidence of oGVHD was 18% (95% CI: 15-21) after myeloablative (MA) and 35% (95% CI: 30-39) after non-myeloablative conditioning (NMA). Factors associated with the rate of oGVHD were assessed separately according to conditioning regimen by using multiple Cox regression analyses. Factors that increased the rate in the MA group: Malignant disease, Schirmer's test≤10 mm/5 min before transplantation, use of female donor, matched unrelated donor, peripheral blood as stem cell source, and grade III-IV acute GVHD. Factors that increased the rate in the NMA group: Schirmer's test≤10 mm/5 min before transplantation and higher recipient age. We recommend a baseline ophthalmological examination before HSCT since many of the patients have signs of dry eyes before transplantation which increased the risk and rate of developing oGVHD.

The Use of Time to Pregnancy for Estimating and Monitoring Human Fecundity From Demographic and Health Surveys.

BACKGROUND: Available studies on the prevalence of infertility have proved to have certain limitations, with a scarcity of population-based studies and inconsistent reporting from surveys in countries at all income levels. We wanted to test the applicability of the current duration approach to data from the important Demographic and Health Surveys (DHS) program, funded by USAID since its inception in 1985, https://dhsprogram.com/. METHODS: The current duration approach assumes that there is a well-defined time of initiation of attempts to get pregnant and defines the current duration of a still ongoing pregnancy attempt as the time interval from initiation to interview. The DHS interviews do not have an explicit question about initiation. We focused on nullipari and substituted date of "establishment of relationship with current partner" for initiation. Our study used the current duration approach on 15 datasets from DHS during 2002-2016 in eight different countries from sub-Saharan Africa, Asia, and Latin America. RESULTS: Well-established statistical techniques for current duration data yielded results that for some countries postulated surprisingly long median times to pregnancy and surprisingly high estimates of infertility prevalence. Further study of the data structures revealed serious deviations from expected patterns, in contrast to our earlier experience from surveys in France and the United States where participants were asked explicitly about time of initiation of attempts to become pregnant. CONCLUSIONS: Using cohabitation as a proxy for the initiation of attempts to get pregnant is too crude. Using the current duration approach with DHS data will require more explicit questions during the DHS interviews about initiation of pregnancy attempt.

Prognostic Value of Soluble Urokinase-Type Plasminogen Activator Receptor and High-Sensitivity C-Reactive Protein on Postoperative Mortality in Patients Undergoing Elective On-Pump Cardiac Surgery.

OBJECTIVES: Elevated soluble urokinase-type plasminogen activator receptor (suPAR) and high-sensitivity C-reactive protein (hsCRP) have been associated with increased mortality in patients with cardiovascular disease. The aim of the present study was to explore the relationship between suPAR and hsCRP values and associated mortality after elective cardiac surgery. A secondary aim was to assess whether a combined risk model of European System for Cardiac Operative Risk Evaluation (EuroSCORE II), suPAR, and/or hsCRP would improve the prognostic accuracy compared with EuroSCORE II alone. DESIGN: Retrospective observational study. SETTING: Single-center, university hospital. PARTICIPANTS: Adult patients admitted for elective on-pump cardiac surgery were included. Biobank blood samples were obtained from previous research projects at a tertiary heart center from 2012 to 2018. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 931 patients were included. Kaplan-Meier and Cox proportional hazard analyses were used to explore a potential association between preoperative suPAR and hsCRP values and all-cause mortality up to one year after surgery. Thirty-day mortality was predicted from suPAR, hsCRP, and EuroSCORE II by logistic regression and compared using area under the receiver operating characteristics curve and Brier scores. After adjustment for known confounders, a doubling of suPAR and hsCRP corresponded to a hazard ratio for all-cause mortality of 2.27 (95% confidence interval 1.65-3.11; p < 0.001) and 1.26 (95% confidence interval 1.07-1.49; p = 0.005), respectively. However, adding the biomarkers to EuroSCORE II did not improve prediction/discrimination with respect to 30-day mortality. CONCLUSIONS: Elevated preoperative levels of suPAR and hsCRP were associated with all-cause mortality in elective cardiac surgery patients. However, inclusion of biomarkers did not improve the prognostic accuracy of EuroSCORE II.

School performance, psychiatric comorbidity, and healthcare utilization in pediatric multiple sclerosis: A nationwide population-based observational study.

BACKGROUND: Pediatric multiple sclerosis (MS) may hamper educational achievements due to psychiatric comorbidity and cognitive impairment. Our aims were to investigate school performance, psychiatric comorbidity, and healthcare utilization following pediatric MS and to differentiate between disability in MS and that arising from a non-brain-related chronic disease. METHODS: We included all children (<18 years) with MS onset during 2008-2015 in Denmark with a medical record-validated MS diagnosis. The control groups were children from the general population or children with non-brain-related chronic diseases. Outcomes were register-based on 9-12 grade point average, psychiatric comorbidity, and healthcare visits. RESULTS: Cohorts were children with MS (n = 92), control children matched to children with MS (n = 920), children with non-brain-related chronic diseases (n = 9108), and "healthy" children with neither MS nor brain-related chronic disease (n = 811,464). School performance in grades 9-12 was similar, but children with MS compared to those with non-brain-related chronic disease had an almost doubled hazard for psychiatric comorbidity (hazard ratio = 1.87; 95% confidence interval = 1.38-2.53; p < 0.0001) and a higher rate of all hospital visits (p < 0.0001) but a lower rate of hospital admissions (p = 0.001). CONCLUSION: Children with MS have a seemingly standard school performance but increased psychiatric comorbidity and a high rate of healthcare utilization.

Mitotic and Proliferative Indices in WHO Grade III Meningioma.

Meningiomas with inherently high mitotic indices and poor prognosis, such as WHO grade III meningiomas, have not been investigated separately to establish interchangeability between conventional mitotic index counted on H&E stained slides (MI) and mitotic index counted on phosphohistone-H3 stained slides (PHH3 MI). This study investigates the agreement of MI and PHH3 MI and to analyze the association of progression-free survival (PFS) and MI, PHH3 MI, and the proliferative index (PI, Ki-67) in WHO grade III meningioma. Tumor specimens from 24 consecutive patients were analyzed for expression of Ki-67, PHH3 MI, and MI. Quantification was performed independently by two observers who made replicate counts in hot spots and overall tumor staining. Repeatability in replicate counts from MI and PHH3 MI was low in both observers. Consequently, we could not report the agreement. MI, PHH3 MI and hot spot counts of Ki-67 were associated with PFS (MI hot spot HR = 1.61, 95% CI 1.12-2.31, p = 0.010; PHH3 MI hot spot HR = 1.59, 95% CI 1.15-2.21, p = 0.006; Ki-67 hot spot HR = 1.06, 95% CI 1.02-1.11. p = 0.004). We found markedly low repeatability of manually counted MI and PHH3 MI in WHO grade III meningioma, and we could not conclude that the two methods agreed. Subsequently, quantification with better repeatability should be sought. All three biomarkers were associated with PFS.

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

Background: Adult overweight is a potential bladder cancer (BC) risk factor, but little is known about size earlier in life.Aim: To investigate if birth weight, childhood body mass index (BMI), height and growth are associated with adult BC.Subjects and methods: 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.Results: 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.Conclusions: A high BMI, a short height, excess BMI gain in childhood and low and high birth weights are associated with increased hazards of BC.