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Objective. In addition to hepatocellular cancer, HFE C282Y homozygotes are reported to have increased risk of colorectal cancer and breast cancer. This study was done to further explore the cancer risk in C282Y homozygotes. Material and methods. We studied cancer incidence in 292 homozygotes and 62,568 others that participated in the HUNT 2 population screening in 1995-1997. Using Cox proportional hazard models, we estimated cancer hazard ratio as a function of C282Y homozygosity and several screening variables including serum transferrin saturation, alcohol consumption and daily smoking. Results. Cancer was diagnosed in 36 homozygotes, five of which had two cancer diagnoses. The overall cancer incidence was not increased in C282Y homozygotes (hazard ratio 1.10 [95% CI 0.60-2.03] in women and 0.94 [95% CI 0.53-1.66] in men). However, homozygous men had increased risk of colorectal cancer (hazard ratio 3.03 [95% CI 1.17-7.82], p = 0.022) and primary liver cancer (hazard ratio 54.0 [95% CI 2.68-1089], p = 0.009). The risk of breast cancer in homozygous women was not increased (hazard ratio 1.13 [95% CI 0.35-3.72]). Adjusted for other variables including C282Y homozygosity, very low and very high serum transferrin saturation were associated with increased overall cancer incidence. Conclusions. C282Y homozygosity is associated with increased risk of colorectal cancer and hepatocellular cancer in men. In the general population, individuals with a very low or a very high serum transferrin saturation may have increased cancer risk. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effectiveness of contemporary mammography screening using individual information about screening history and breast cancer mortality from public screening programmes. Design: Prospective cohort study of Norwegian women who were followed between 1986 and 2009. Within that period (1995-2005), a national mammography screening programme was gradually implemented, with biennial invitations sent to women aged 50-69 years. Participants: All Norwegian women aged 50-79 between 1986 and 2009. Main outcome measures Multiple Poisson regression analysis was used to estimate breast cancer mortality rate ratios comparing women who were invited to screening (intention to screen) with women who were not invited, with a clear distinction between cases of breast cancer diagnosed before (without potential for screening effect) and after (with potential for screening effect) the first invitation for screening. We took competing causes of death into account by censoring women from further follow-up who died from other causes. Based on the observed mortality reduction combined with the all cause and breast cancer specific mortality in Norway in 2009, we used the CISNET (Cancer Intervention and Surveillance Modeling Network) Stanford simulation model to estimate how many women would need to be invited to biennial mammography screening in the age group 50-69 years to prevent one breast cancer death during their lifetime. Results: During 15 193 034 person years of observation (1986-2009), deaths from breast cancer occurred in 1175 women with a diagnosis after being invited to screening and 8996 women who had not been invited before diagnosis. After adjustment for age, birth cohort, county of residence, and national trends in deaths from breast cancer, the mortality rate ratio associated with being invited to mammography screening was 0.72 (95% confidence interval 0.64 to 0.79). To prevent one death from breast cancer, 368 (95% confidence interval 266 to 508) women would need to be invited to screening. Conclusion: Invitation to modern mammography screening may reduce deaths from breast cancer by about 28%.

Introduction: The association between cervical cancer screening and reduction of cervical cancer has been dealt with in much research. However, little has been published on the association between screening and cervical cancer mortality. We assessed cervical cancer deaths according to screening history, histopathology, and age among women in, under, and above screening age. Material and methods: In this nationwide, registry‐based case–control study from Norway, we included 817 cervical cancer deaths in women diagnosed with cervical cancer in the period 1998–2009. We matched each case with 10 population‐based controls free from cervical cancer, obtained by density‐based sampling. Odds ratios (ORs) with 95% confidence intervals (CIs) for the association between screening attendance and cervical cancer mortality were estimated using conditional logistic regression models. Results: Of all fatal cervical cancers, 35% were diagnosed among women over screening age and altogether, 83% were either in age groups not covered by the screening program or in non‐attenders of screening age. The estimated risk reduction associated with a cytology test in the preceding 3.5 years was 80% in screening age 25–69 years (OR 0.20; 95% CI 0.16–0.24) with the largest reduction in squamous cell carcinomas (84%) but also a substantial estimated risk reduction of 65% for adenocarcinomas. The associated risk reduction was strongest in women aged 45–69 years, with ORs in the range 0.09–0.18, compared with ORs 0.42–1.35 in women aged 25–39 years. Conclusions: To reduce the mortality of cervical cancer, screening programs should focus on increasing adherence to the program, as half of all the fatal cases were in the non‐attender group. Further assessments regarding the potential preventive impact of extending screening to women over the current screening age should be considered. [ABSTRACT FROM AUTHOR]

The delayed development of abdominal aortic aneurysm (AAA) in women compared with men might be secondary to a protective effect from endogenous estrogens. The role of postmenopausal hormone therapy remains unclear. The aim of the present study was to evaluate the effect of female sex hormones compared with other risk factors associated with AAA through a long-term study of a large female cohort. The present prospective cohort study included 20,024 postmenopausal women from the Norwegian Nord-Trøndelag Health Study. A total of 201 cases of AAA were identified during a median follow-up period of 18 years (295,554 person-years; 1995-2014). The data were recorded from questionnaires, physical measurements, medical records, blood sample test results, and the Norwegian Cause of Death Registry. The effect of risk factors was evaluated in a multiple Cox regression analysis. Multiple imputation was performed for missing data (n = 50 data sets). The serum estradiol concentrations in women with and without incidental AAAs were compared. The median interval from blood sample collection to the AAA diagnosis was 7 years. Current smokers had >10-fold increased risk of incident AAA during the follow-up period (hazard ratio [HR], 10.9; 95% confidence interval [CI], 7.4-16.1). Positive associations were found for hypertension (HR, 2.0; 95% CI, 1.4-3.0) and coronary heart disease (HR, 2.2; 95% CI, 1.6-3.2). The HR associated with the current use of postmenopausal hormone therapy was 0.58 (95% CI, 0.6-1.5). No substantial difference in estradiol concentrations was found between women with and without AAA (P =.075). The effect of female sex hormones on the risk of incident AAAs in women, as evaluated by the serum concentrations of estradiol and the use of postmenopausal hormone therapy, is clinically less important than the strong associations found with smoking, hypertension, and coronary heart disease. [ABSTRACT FROM AUTHOR]

Background: Vitamin D insufficiency is common in pregnant women worldwide. Regular prenatal exercise is considered beneficial for maternal and fetal health. There is a knowledge gap regarding the impact of prenatal exercise on maternal vitamin D levels. The objective of this study was to investigate whether a prenatal exercise program influenced serum levels of total, free and bioavailable 25-hydroxyvitamin D (25(OH)D) and related parameters. This is a post hoc analysis of a randomized controlled trial with gestational diabetes as the primary outcome.Methods: Healthy, pregnant women from two Norwegian cities (Trondheim and Stavanger) were randomly assigned to a 12-week moderate-intensity exercise program (Borg perceived rating scale 13-14) or standard prenatal care. The intervention group (n = 429) underwent exercise at least three times weekly; one supervised group training and two home based sessions. The controls (n = 426) received standard prenatal care, and exercising was not denied. Training diaries and group training was used to promote compliance and evaluate adherence. Serum levels of 25(OH)D, parathyroid hormone, calcium, phosphate, magnesium and vitamin D-binding protein were measured before (18-22 weeks' gestation) and after the intervention (32-36 weeks' gestation). Free and bioavailable 25(OH)D concentrations were calculated. Regression analysis of covariance (ANCOVA) was applied to assess the effect of the training regime on each substance with pre-intervention levels as covariates. In a second model, we also adjusted for study site and sampling month. Intention-to-treat principle was used.Results: A total of 724 women completed the study. No between-group difference in serum 25(OH)D and related parameters was identified by ANCOVA using baseline serum levels as covariates. The second model revealed a between-group difference in levels of 25(OH)D (1.9, 95% CI 0.0 to 3.8 nmol/L; p = 0.048), free 25(OH)D (0.55, 95% CI 0.10 to 0.99 pmol/L; p = 0.017) and bioavailable 25(OH)D (0.15 95% CI 0.01 to 0.29 nmol/L; p = 0.036). No serious adverse events related to regular exercise were seen.Conclusion: This study, a post hoc analysis, indicates that exercise may affect vitamin D status positively, and emphasizes that women with uncomplicated pregnancies should be encouraged to perform regular exercise.Trial Registration: ClinicalTrials.gov: NCT00476567 , registered May 22, 2007. [ABSTRACT FROM AUTHOR]

Background: The role of normal tissue gene promoter methylation in cancer risk is poorly understood.Objective: To assess associations between normal tissue BRCA1 methylation and ovarian cancer risk.Design: 2 case-control (initial and validation) studies.Setting: 2 hospitals in Norway (patients) and a population-based study (control participants).Participants: 934 patients and 1698 control participants in the initial study; 607 patients and 1984 control participants in the validation study.Measurements: All patients had their blood sampled before chemotherapy. White blood cell (WBC) BRCA1 promoter methylation was determined by using methylation-specific quantitative polymerase chain reaction, and the percentage of methylation-positive samples was compared between population control participants and patients with ovarian cancer, including the subgroup with high-grade serous ovarian cancer (HGSOC).Results: In the initial study, BRCA1 methylation was more frequent in patients with ovarian cancer than control participants (6.4% vs. 4.2%; age-adjusted odds ratio [OR], 1.83 [95% CI, 1.27 to 2.63]). Elevated methylation, however, was restricted to patients with HGSOC (9.6%; OR, 2.91 [CI, 1.85 to 4.56]), in contrast to 5.1% and 4.0% of patients with nonserous and low-grade serous ovarian cancer (LGSOC), respectively. These findings were replicated in the validation study (methylation-positive status in 9.1% of patients with HGSOC vs. 4.3% of control participants-OR, 2.22 [CI 1.40 to 3.52]-4.1% of patients with nonserous ovarian cancer, and 2.7% of those with LGSOC). The results were not influenced by tumor burden, storage time, or WBC subfractions. In separate analyses of young women and newborns, BRCA1 methylation was detected in 4.1% (CI, 1.8% to 6.4%) and 7.0% (CI, 5.0% to 9.1%), respectively.Limitations: Patients with ovarian cancer were recruited at the time of diagnosis in a hospital setting.Conclusion: Constitutively normal tissue BRCA1 promoter methylation is positively associated with risk for HGSOC.Primary Funding Source: Norwegian Cancer Society. [ABSTRACT FROM AUTHOR]

A history of preterm or small (SGA) or large (LGA) for gestational age offspring is associated with smoking and unfavorable levels of BMI, blood pressure, glucose and lipids. Whether and to what extent the excess cardiovascular risk observed in women with these pregnancy complications is explained by conventional cardiovascular risk factors (CVRFs) is not known. We examined the association between a history of SGA, LGA or preterm birth and cardiovascular disease among 23,284 parous women and quantified the contribution of individual CVRFs to the excess cardiovascular risk using an inverse odds weighting approach. The hazard ratios (HR) between SGA and LGA offspring and CVD were 1.30 (95% confidence interval (CI) 1.15, 1.48) and 0.89 (95% CI 0.76, 1.03), respectively. Smoking explained 49% and blood pressure may have explained ≈12% of the excess cardiovascular risk in women with SGA offspring. Women with preterm birth had a 24% increased risk of CVD (HR 1.24, 95% CI 1.06, 1.45), but we found no evidence for CVRFs explaining any of this excess cardiovascular risk. While smoking explains a substantial proportion of excess cardiovascular risk in women with SGA offspring and blood pressure may explain a small proportion in these women, we found no evidence that conventional CVRFs explain any of the excess cardiovascular risk in women with preterm birth. [ABSTRACT FROM AUTHOR]

Women with small or large for gestational age offspring are at increased risk of cardiovascular disease later in life. How their cardiovascular risk factors develop across the life course is incompletely known. We linked data from the population-based HUNT Study (1984–2008) and the Medical Birth Registry of Norway (1967–2012) for 22,487 women. Mixed effect models were used to compare cardiovascular risk factor trajectories for women according to first offspring birthweight for gestational age. Women with small for gestational age (SGA) offspring had 1–2 mmHg higher systolic and diastolic blood pressure across the life course, but lower measures of adiposity, compared to women with offspring who were appropriate for gestational age (AGA). In contrast, women with large for gestational age (LGA) offspring had higher measures of adiposity, ~0.1 mmol/l higher non-HDL cholesterol and triglycerides and 0.2 mmol/l higher non-fasting glucose, compared with mothers of AGA offspring. These differences were broadly stable from prior to first pregnancy until 60 years of age. Our findings point to different cardiovascular risk profiles in mothers of SGA versus LGA offspring, where giving birth to SGA offspring might primarily reflect adverse maternal vascular health whereas LGA offspring might reflect the mother's metabolic health. [ABSTRACT FROM AUTHOR]

Background To compare associations of conventional risk factors with cardiovascular death within couples and in the population as a whole. Methods We analysed baseline data (1995–97) from the HUNT2 Study in Norway linked to the national Causes of Death Registry. We compared risk within couples using stratified Cox regression. Results During 914776 person-years, 3964 cardiovascular deaths occurred, and 1658 of the deaths occurred among 1494 couples. There were consistently stronger associations of serum lipids and blood pressure with cardiovascular mortality within couples compared to the population as a whole. For instance, for systolic blood pressure (per 20 mm Hg), the hazard ratio (HR) within couples was 1.28 (95% confidence interval: 1.17, 1.40) compared to 1.16 (1.12, 1.20) in the total population, and for diastolic pressure (per 10 mm Hg), the corresponding HRs were 1.16 (1.07, 1.26) and 1.11 (1.08, 1.13). Anthropometric factors (BMI, waist circumference, waist-hip ratio) as well as diabetes, smoking, physical activity, and education, showed nearly identical positive associations within couples and in the total population. Conclusions Prospective population studies may tend to slightly underestimate associations of these factors with cardiovascular mortality. [ABSTRACT FROM AUTHOR]

ABSTRACT Background and objective People with asthma may seek advice about physical activity. However, the benefits of leisure time physical activity on lung function are unclear. We investigated the association between leisure time physical activity and lung function decline in adults with asthma. Methods In a population-based cohort study in Norway, we used multiple linear regressions to estimate the annual mean decline in lung function (and 95% CI) in 1329 people with asthma over a mean follow-up of 11.6 years. The durations of light and hard physical activity per week in the last year were collected by questionnaire. Inactive participants did not report any light or hard activity, while active participants reported light or hard activity. Results The mean decline in forced expiratory volume in 1 s ( FEV1 ) was 37 mL/year among inactive participants and 32 mL/year in active participants (difference: −5 mL/year (95% CI: −13 to 3)). The mean decline in forced vital capacity ( FVC) was 33 mL/year among inactive participants and 31 mL/year in active participants (difference: −2 mL/year (95% CI: −11 to 7)). The mean decline in FEV1 / FVC ratio was 0.36%/year among inactive participants and 0.22%/year in active participants (difference: −0.14%/year (95% CI: −0.27 to −0.01)). The mean decline in peak expiratory flow ( PEF) was 14 mL/year among the inactive participants and 10 mL/year in active participants (difference: −4 mL/year (95% CI: −9 to 1)). Conclusion We observed slightly less decline in lung function in physically active than inactive participants with asthma, particularly for FEV1, FEV1/ FVC ratio and PEF. [ABSTRACT FROM AUTHOR]

Introduction: Women with a history of hypertensive disorders of pregnancy (HDP) have an increased risk of cardiovascular disease (CVD). It is uncertain how much of the excess CVD risk in women with a history of HDP that is explained by conventional cardiovascular risk factors. Aims: In this study we aimed to quantify the excess risk of CVD in women with a history of HDP, and estimate the proportion explained by adverse levels of conventional, modifiable cardiovascular risk factors: body mass index (BMI), blood pressure, glucose and lipids. Methods: We linked data from the population-based HUNT Study, validated hospital records, the Cause of Death Registry and the Medical Birth Registry of Norway for 21 766 women with normotensive pregnancies and 2199 women with a history of HDP. We used Cox proportional hazards models to estimate the hazard ratio (HR) for CVD comparing women with and without a history of HDP, and an inverse odds ratio weighting approach to estimate the proportion of excess risk in women with a history of HDP that was explained by conventional CVD risk factors. Results: From age 40 to 70, women with a history of HDP had an increased risk of CVD compared to women with only normotensive pregnancies (HR=1.57, 95% confidence interval: 1.32-1.87), but not at older age (p for interaction by age=0.015). Blood pressure and BMI accounted for up to 77% of the excess risk of CVD in women with history of HDP, while glucose and lipids accounted for smaller proportions. Conclusion: The excess risk of CVD in women with history of HDP is largely explained by conventional cardiovascular risk factors, in particular hypertension and adiposity, indicating that these risk factors are important targets for cardiovascular prevention in women with history of HDP. [ABSTRACT FROM AUTHOR]

Introduction: Psoriasis has been associated with greater adiposity, but the direction of causality has not been established. Aims: We aimed to investigate a possible causal relationship between body mass index (BMI) and psoriasis using Mendelian Randomization (MR). Methods: We used a genetic instrument for BMI comprising 97 single nucleotide polymorphisms (SNPs), and conducted one-sample MR using individual-level data from 401,171 individuals in the UK Biobank and the Nord-Trøndelag Health Study (HUNT), Norway. We also performed two-sample MR with summary-level data (356,926 individuals) from published BMI and psoriasis GWA studies, and meta-analysed the one-sample and two-sample MR estimates using a fixed effect model. To explore a potential reverse causal direction, we conducted MR analyses with genetic instruments comprising variants from recent genome-wide analyses for psoriasis to examine if genetic liability to psoriasis has an effect on BMI. Results: In observational analyses, higher measured BMI was associated a higher prevalence of psoriasis in both UK Biobank and HUNT (meta-analysis OR 1.04 (95% CI 1.03-1.04) per 1 kg/m² higher BMI; P=1.73×10-60). MR analyses provided evidence that higher BMI causally increases the odds of psoriasis (OR 1.09 (95% CI 1.06-1.12) per 1 kg/m² higher BMI; P=4.67×10-9). In contrast, MR estimates provided evidence for only a small effect of genetic risk of psoriasis on BMI (0.03 kg/m² (95% CI 0.01-0.06) higher BMI per doubling odds of psoriasis; P=0.01). Conclusions: Our study, using genetic variants as instrumental variables for BMI, shows that higher BMI leads to a higher risk of psoriasis. Therapies and lifestyle interventions aimed at controlling weight should be further prioritised for the prevention or treatment of psoriasis. [ABSTRACT FROM AUTHOR]

Aims: A low resting heart rate (RHR) implies a more efficient heart function and a lower risk of cardiovascular disease. However, observational studies have reported a U-shaped association between RHR and atrial fibrillation (AF). In contrast, Mendelian randomization (MR) studies have found an inverse causal association between RHR and AF. Hence, the causal nature of the relationship is not clear. The aim is to investigate the causal association and its shape between RHR on AF using linear and non-linear MR (NLMR)., Methods and Results: Linear and non-linear MR were performed on individual-level data in the Trøndelag Health Study (HUNT) and UK Biobank (UKB). HUNT consists of 69 155 individuals with 7,062 AF cases, while UKB provides data on 431 852 individuals with 20 452 AF cases. The linear MR found an inverse relationship between RHR and AF with an OR = 0.95 [95% confidence interval (CI): 0.93-0.98] and OR = 0.96 (95% CI: 0.95-0.97) per unit decrease in RHR in HUNT and UKB, respectively. The NLMR was supportive of an inverse linear relationship in both HUNT and UKB for RHR values <90 beats per minute (bpm). Several sensitivity analyses were also consistent., Conclusion: In contrast with the current observational knowledge of RHR and AF, an inverse causal association between RHR and AF was demonstrated in both linear and non-linear MR for RHR values up to 90 bpm. Further exploring the underlying mechanisms of the genetic instrument for RHR may shed light on whether pleiotropy is biasing this association., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background and Purpose- We wanted to evaluate potential risk factors for unruptured intracranial aneurysms (UIAs) and aneurysmal subarachnoid hemorrhage (aSAH) in a large, prospective study of the general population with risk factors collected before the detection of UIA or aSAH. Methods- All residents ≥20 years were invited to the HUNT (The Nord-Trøndelag Health Study). In this study, 89 951 participants were included. The study included standardized measurements of blood pressure and self-administered questionnaires. Cases of UIA and aSAH from 1999 to 2014 were identified using hospital records and the Norwegian Cause of Death Register. Hazard ratios with CIs were estimated using Cox regression analysis. Results- The detection rate of UIA was 8.2 per 100 000 person-years (97 patients). Current smoking (hazard ratio, 4.1; 95% CI, 2.4-7.1) and female sex (hazard ratio, 2.8; 95% CI, 1.7-4.5) were associated with markedly increased risk of UIA, but we found no association with systolic blood pressure ( P for trend 0.62). The incidence of aSAH was 9.9 per 100 000 person-years (117 patients). The most important risk factors for aSAH were current smoking, female sex and increasing blood pressure ( P for trend 0.006 for systolic blood pressure). Conclusions- In contrast to previous studies on risk factors of UIA, we found no association with systolic blood pressure. However, there was a strong association between systolic blood pressure and aSAH in the same population. Current smoking and female sex were associated with both diseases.

Few studies have investigated the association between serum 25-hydroxyvitamin D (25[OH]D), vitamin D supplement and asthma control among adults. We aimed to examine whether low levels of serum 25(OH)D or not taking vitamin D supplement were associated with an increased risk of poorly controlled asthma among Norwegian adults with asthma. We used a definition of asthma control adapted from the Global Initiative for Asthma. We first examined cross-sectional associations between serum 25(OH)D (n = 806) or vitamin D supplement (n = 1179) and poorly controlled asthma. Next, among those with well controlled asthma at baseline, we examined prospective associations between serum 25(OH)D (n = 147) or vitamin D supplement (n = 208) and poorly controlled asthma at follow-up, approximately 11 years later. We estimated risk ratios (RR) and 95% confidence intervals (CI) with Poisson regression. The adjusted RR for poorly controlled asthma was 1.00 (95% CI, 0.89-1.13) for adults with serum 25(OH)D < 50 nmol/L in cross-sectional and 1.50 (95% CI, 0.46-4.95) in prospective analyses. The adjusted RR for poorly controlled asthma was 1.17 (95% CI 1.00-1.37) for non-users of vitamin D supplement in cross-sectional and 1.66 (95% CI 0.49-5.67) in prospective analyses. Our study did not show strong evidence that among adults with asthma, having a low serum 25(OH)D or being a non-user of vitamin D supplement was associated with an increased risk of poorly controlled asthma. Some point estimates indicated an increased risk, however our estimates were generally imprecise and further evidence is needed., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Although psoriasis has been associated with obesity, there are few prospective studies with objective measures. We prospectively examined the effect of body mass index, waist circumference, waist-hip ratio, and 10-year weight change on the risk of developing psoriasis among 33,734 people in the population-based Nord-Trøndelag Health Study (i.e., HUNT), Norway. During follow-up, 369 incident psoriasis cases occurred. Relative risk (RR) of psoriasis was estimated by Cox regression. One standard deviation higher body mass index, waist circumference, and waist-hip ratio gave RRs of 1.22 (95% confidence interval [CI] = 1.11-1.34), 1.26 (95% CI = 1.15-1.39), and 1.18 (95% CI = 1.07-1.31), respectively. Compared with normal weight participants, obese people had an RR of 1.87 (95% CI = 1.38-2.52), whereas comparing the fourth with the first quartile of waist circumference gave an RR of 1.95 (95% CI = 1.46-2.61). One standard deviation higher weight change gave an RR of 1.20 (95% CI = 1.07-1.35), and people who increased their body weight by 10 kg or more had an RR of 1.72 (95% CI = 1.15-2.58) compared with being weight stable. In conclusion, obesity and high abdominal fat mass doubles the risk of psoriasis, and long-term weight gain substantially increases psoriasis risk. Preventing weight gain and promoting maintenance of a normal body weight could reduce incidence of psoriasis., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate self-reported pain in young adults with a low birth weight., Materials and Methods: This study was a part of a long-term follow-up study of preterm very low birth weight (VLBW; birth weight ≤1500 g), term small for gestational age (SGA; birth weight <10th percentile adjusted for sex and parity), and control young adults born during 1986 to 1988. Of the 300 individuals invited, 216 (62 VLBW, 67 term SGA, and 87 controls) completed a pain questionnaire. Of these, 151 (70%) had answered a pain severity question at 19 years. Chronic pain was defined as pain lasting for >6 months and being moderate, severe, or very severe during the past 4 weeks., Results: The prevalence of chronic pain at 26 years was 16% in the VLBW group, 21% in the term SGA group, and 7% in the control group. The VLBW and the term SGA groups had higher odds ratios for chronic pain (crude OR, 2.6; 95% CI, 0.9-7.6 for the VLBW group and crude OR, 3.6; 95% CI, 1.3-9.9 for the term SGA group vs. controls). The main results remained after adjusting for potential confounding factors. Some attenuation was observed when adjusting for anxiety and depressive problems. Moderate to very severe pain increased from 16% to 41% in the term SGA group from 19 to 26 years, whereas less changes were seen in the VLBW and the control groups., Discussion: Results of our study imply that pain should be in focus when conducting long-term follow-up programs of individuals with a low birth weight.

Purpose: Breast cancer can be classified into molecular subtypes that differ in clinical characteristics and prognosis. There is some but conflicting evidence that reproductive risk factors may differ between distinct breast cancer subtypes., Methods: We investigated associations of reproductive factors with the risk for six molecular breast cancer subtypes in a cohort of 21,532 Norwegian women who were born between 1886 and 1928 and followed up for breast cancer incidence between 1961 and 2008. We obtained stored tumor tissue from incident breast cancers and used immunohistochemistry and in situ hybridization to classify 825 invasive tumors into three luminal subtypes [Luminal A, Luminal B (HER2-) and Luminal B (HER2+)] and three non-luminal subtypes [human epidermal growth factor receptor 2 (HER2) subtype, basal-like phenotype (BP) and five negative phenotype (5NP)]. We used Cox regression to assess reproductive factors and risk for each subtype., Results: We found that young age at menarche, old age at first birth and low parity were associated with increased risk for luminal breast cancer subtypes. For the HER2 subtype, we either found no association or associations in the opposite direction compared to the luminal subtypes. The BP subtype appeared to have a similar reproductive risk profile as the luminal subtypes. Breastfeeding was associated with a reduced risk for HER2 and 5NP subtypes, but was not associated with any other subtype., Conclusions: The results suggest that molecular breast cancer subtypes differ in their reproductive risk factors, but associations with non-luminal subtypes are still poorly understood and warrant further study.

Maternal angiogenic factors (placental growth factor, soluble fms-like tyrosine kinase 1 (Flt-1), and soluble endoglin) may be associated with fetal growth restriction, and the associations may differ according to stage of pregnancy. Among children born to pregnant women without preeclampsia in Norway between 1992 and 1994, 217 singletons with severe growth restriction (small for gestational age (SGA), <2.5th percentile) were compared with 378 singleton controls. For each angiogenic factor, SGA risk was related to concentrations in maternal serum collected in the first 2 trimesters, by using women with a serum concentration in the middle third at both samplings as reference. A low placental growth factor (lowest third) at both samplings was associated with high risk of SGA (odds ratio=3.8, 95% confidence interval: 1.6, 8.8). An increase from the lowest to the highest third of soluble Flt-1 was associated with high SGA risk (odds ratio=6.2, 95% confidence interval: 2.4, 16.1). Women with high soluble endoglin (highest third) at the second sampling had approximately a 3.5-fold increased risk of SGA. Low maternal soluble Flt-1 in early pregnancy followed by a strong subsequent increase in soluble Flt-1 and soluble endoglin was associated with a particularly high risk of severe fetal growth restriction., (© The Author 2011. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved.)

Background: An explanation for the increased risk of myocardial infarction and stroke in patients with venous thrombosis is lacking. The objective of this study was to investigate whether risk factors for arterial cardiovascular disease also increase the risk of venous thrombosis., Design and Methods: Cases who had a first venous thrombosis (n=515) and matched controls (n=1,505) were identified from a population-based, nested, case-cohort study (the HUNT 2 study) comprising 71% (n=66,140) of the adult residents of Nord-Trøndelag County in Norway., Results: The age- and sex-adjusted odds ratio of venous thrombosis for subjects with concentrations of C-reactive protein in the highest quintile was 1.6 (95% confidence interval: 1.2-2.2) compared to subjects with C-reactive protein in the lowest quintile. This association was strongest in subjects who experienced venous thrombosis within a year after blood sampling with a three-fold increased risk of participants in the highest versus the lowest quintile. Having first degree relatives who had a myocardial infarction before the age of 60 years was positively associated with venous thrombosis compared to not having a positive family history [odds ratio 1.3 (95% confidence interval: 1.1-1.6)]. Subjects with blood pressure in the highest quintile had half the risk of developing venous thrombosis compared to subjects whose blood pressure was in the lowest quintile. There were no associations between the risk of venous thrombosis and total cholesterol, low density lipoprotein-cholesterol, high density lipoprotein-cholesterol, triglycerides, glucose or smoking. We confirmed the positive association between obesity and venous thrombosis., Conclusions: C-reactive protein and a family history of myocardial infarction were positively associated with subsequent venous thrombosis. Blood pressure was inversely correlated to venous thrombosis. These findings should be confirmed by further investigations.

Objective: To compare blood pressure (BP) in adolescence (11-12 years) among the offspring of preeclamptic and normotensive pregnancies., Method: SBP and DBP of 181 girls and boys born after pregnancies with preeclampsia were measured and compared with the BP of 356 age-matched girls and boys of normotensive pregnancies. The association of preeclampsia with later BP was adjusted for perinatal information, anthropometric factors at follow-up, and maternal BP and BMI., Results: In the preeclampsia group, SBP in early adolescence was higher than in the normotensive group (115.3 vs. 113.5 mmHg, P = 0.03), but there was no difference in DBP (66.4 vs. 65.3 mmHg, P = 0.10). After adjustment for maternal body mass and BP, the difference in SBP was largely attenuated., Conclusion: The higher SBP among adolescent offspring of preeclamptic pregnancies could be mediated by maternal body mass or BP, factors that are positively associated with the risk of preeclampsia in pregnancy.

This case-cohort designed study prospectively investigated whether elevated homocysteine levels measured in blood samples drawn before the event and methylenetetrahydrofolate reductase (MTHFR) gene polymorphism (MTHFR C677T) were associated with subsequent first venous thrombosis (VT) in a general population. Between August 1995 and June 1997, blood was collected from 66 140 people in the second Norwegian Health Study of Nord-Trøndelag (HUNT2). During a seven-year follow-up, 505 VT cases were identified. 1458 age- and sex-matched controls were selected from the original cohort. Serum total homocysteine (tHcy) and MTHFR genotype were measured in stored samples that were drawn a median of 33 months before the events. The overall odds ratio (OR) was 1.50 [95% confidence interval (CI) 0.97-2.30] for homocysteine levels above versus below the 95th percentile. There was no graded association with VT over quintiles of homocysteine. In men the OR was 2.17 (95% CI 1.20-3.91) for levels above versus below the 95th percentile, but no association was found in women (OR 1.00). Stratification by age, predisposing risk factors or time to event did not change these results. The MTHFR 677TT genotype was not related to risk for VT. In conclusion, elevated homocysteine levels in the general population predicted subsequent first VT in men but not in women.

Early age at menarche and tallness are associated with increased risk for breast cancer, and emerging evidence suggests that body size at birth also is positively associated with breast cancer risk in adulthood. We have explored whether this effect of birth size could be mediated by influencing age at menarche or body height during adolescence. Information on age at menarche and adolescent height among 3,343 Norwegian girls 13 to 19 years of age, born at term and whose mothers had no history of gestational disease was individually linked to information on birth weight and length recorded in the national Medical Birth Registry. We related quintiles of birth size, adjusted for length of gestation, to age at menarche and adolescent height and weight, using general linear modeling and Cox regression analyses. In a subsample of the population, we also had information on maternal age at menarche, as well as adult height and body mass index in both parents. We explored whether parental factors confounded the association between perinatal predictors and adolescent outcomes in the daughters. We found that age at menarche tended to occur earlier with decreasing birth weight (p for trend = 0.03), and girls who were thin at birth (i.e., in the lowest quintile of ponderal index) had an earlier age at menarche than other girls (p = 0.02). Weight and length at birth were strongly and positively related to tallness during adolescence (p for trend < 0.001), but ponderal index, indicating obesity at birth, was negatively associated with adolescent height (p for trend = 0.002). Adjustment for parental height, body mass index and maternal age at menarche, in the subsample where this information was available, indicated no substantial confounding by these parental factors. Our results suggest that a positive association between birth size and adult breast cancer is not likely to be mediated by early age at menarche, but possibly by increased body height in adolescence., (Copyright 2003 Wiley-Liss, Inc.)