Publications by authors named "Pal R Romundstad"

96 Publications

Life Course Trajectories of Maternal Cardiovascular Risk Factors according to Offspring Birthweight: The HUNT Study.

Sci Rep 2020 06 26;10(1):10436. Epub 2020 Jun 26.

K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Norwegian University of Science and Technology, Trondheim, Norway.

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.
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http://dx.doi.org/10.1038/s41598-020-66365-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7319986PMC
June 2020

Risk Factors for Unruptured Intracranial Aneurysms and Subarachnoid Hemorrhage in a Prospective Population-Based Study.

Stroke 2019 10 2;50(10):2952-2955. Epub 2019 Aug 2.

Department of Cancer and Palliative Care, Nordland Hospital Bodø, Norway (M.S.S.).

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 ( 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 ( 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.
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http://dx.doi.org/10.1161/STROKEAHA.119.025951DOI Listing
October 2019

Female sex hormones and risk of incident abdominal aortic aneurysm in Norwegian women in the HUNT study.

J Vasc Surg 2019 11 24;70(5):1436-1445.e2. Epub 2019 Jun 24.

Department of Vascular Surgery, St. Olavs Hospital, Trondheim, Norway; Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway.

Objective: 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.

Methods: 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.

Results: 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).

Conclusions: 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.
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http://dx.doi.org/10.1016/j.jvs.2019.02.032DOI Listing
November 2019

Association of Conventional Cardiovascular Risk Factors With Cardiovascular Disease After Hypertensive Disorders of Pregnancy: Analysis of the Nord-Trøndelag Health Study.

JAMA Cardiol 2019 07;4(7):628-635

K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Norwegian University of Science and Technology, Trondheim, Norway.

Importance: Women with a history of hypertensive disorders of pregnancy (HDP) have higher risk of cardiovascular disease (CVD). It is not known how much of the excess CVD risk in women with a history of HDP is associated with conventional cardiovascular risk factors.

Objective: To quantify the excess risk of CVD in women with a history of HDP and estimate the proportion associated with conventional cardiovascular risk factors.

Design, Setting, And Participants: Prospective cohort study with a median follow-up of 18 years. Population-based cohort of women participating in the Nord-Trøndelag Health Study in Norway. We linked data for 31 364 women from the Nord-Trøndelag Health Study (1984-2008) to validated hospital records (1987-2015), the Cause of Death Registry (1984-2015), and the Medical Birth Registry of Norway (1967-2012). A total of 7399 women were excluded based on selected pregnancy characteristics, incomplete data, or because of emigrating or experiencing the end point before start of follow-up, leaving 23 885 women for study. Data were analyzed between January 1, 2018, and June 6, 2018.

Exposures: Experiencing 1 or more pregnancies complicated by HDP before age 40 years vs only experiencing normotensive pregnancies.

Main Outcomes And Measures: We used Cox proportional hazards models to estimate the hazard ratios (HRs) for the association between HDP and CVD. The proportion of excess risk associated with conventional cardiovascular risk factors was estimated using an inverse odds ratio weighting approach.

Results: Our study population consisted of 23 885 parous women from Nord-Trøndelag County, Norway. A total of 21 766 women had only normotensive pregnancies, while 2199 women experienced ever having an HDP. From age 40 to 70 years, women with history of HDP had an increased risk of CVD compared with women with only normotensive pregnancies (HR, 1.57; 95% CI, 1.32-1.87) but not at older age (β = 0.98; 95% CI, 0.96-1.00; P for interaction by age = .01). Blood pressure and body mass index were associated with up to 77% of the excess risk of CVD in women with history of HDP, while glucose and lipid levels were associated with smaller proportions.

Conclusion And Relevance: In this study, the risk of excess CVD in women with history of HDP was associated with conventional cardiovascular risk factors, indicating that these risk factors are important targets for cardiovascular prevention in these women.
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http://dx.doi.org/10.1001/jamacardio.2019.1746DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6563586PMC
July 2019

The effect of an exercise program in pregnancy on vitamin D status among healthy, pregnant Norwegian women: a randomized controlled trial.

BMC Pregnancy Childbirth 2019 Feb 20;19(1):76. Epub 2019 Feb 20.

Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.

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.
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http://dx.doi.org/10.1186/s12884-019-2220-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6381613PMC
February 2019

Clinical performance of Anyplex II HPV28 by human papillomavirus type and viral load in a referral population.

PLoS One 2019 23;14(1):e0210997. Epub 2019 Jan 23.

Faculty of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, Ås, Norway.

Anyplex II HPV28 (`Anyplex`) is a semi-quantitative DNA PCR assay divided into set A, comprising 14 high risk (hr)HPV types; and set B, comprising 5 possibly hrHPV types and 9 low risk (lr)HPV types. We compared the ability of Anyplex to that of Hybrid Capture 2 (HC2) and PreTect HPV-Proofer (`Proofer`) to detect cervical intraepithelial neoplasia grade two or worse (CIN2+) by HPV types and viral load. This cross-sectional study included 296 women referred to colposcopy with abnormal cervical cytology and/or persistent HPV infection. CIN2+ was identified in 175/296 women. Liquid based cytology samples were used to perform HPV testing. The sensitivity of Anyplex to detect CIN2+ was 98.9% (95% CI 95.9-99.9) and specificity 43.0% (95% CI 34.0-52.3). Restricting to medium and high viral loads in Anyplex set A, sensitivity and specificity were 97.1% (95% CI 93.5-99.1) and 59.5% (95% CI 50.2-68.3) with positive (PPV) and negative predictive value (NPV) 77.6% and 93.5%, respectively, comparable to HC2. Restricting Anyplex to the hrHPV types in Proofer, HPV16, 18, 31, 33 and 45, sensitivity and specificity for CIN2+ were 85.1% (95% CI 79.0-90.1) and 71.1% (95% CI 62.1-79.0), comparable to Proofer`s. When adding HPV52 and 58, the sensitivity for CIN2+ was 92.6% (95% CI 87.6-96.0) and CIN3+ 96.5% (95% CI 92.0-98.8). No value of Anyplex set B was found in detecting CIN2+. In conclusion, the clinical performance of medium and high viral loads in Anyplex set A was comparable to HC2. Restricting the test to the 7 hrHPV types included in the 9-valent HPV-vaccine, HPV16, 18, 31, 33, 45, 52 and 58, satisfies the international criteria for cervical cancer screening with relative sensitivity compared to HC2 for CIN2+ and CIN3+ of 0.98 and 1.01, respectively. Detecting all 28 Anyplex HPV types adds no benefit in a referral population.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0210997PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6343909PMC
November 2019

Does pregnancy complication history improve cardiovascular disease risk prediction? Findings from the HUNT study in Norway.

Eur Heart J 2019 04;40(14):1113-1120

K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Postboks 8905, Trondheim, Norway.

Aim: To evaluate whether history of pregnancy complications [pre-eclampsia, gestational hypertension, preterm delivery, or small for gestational age (SGA)] improves risk prediction for cardiovascular disease (CVD).

Methods And Results: This population-based, prospective cohort study linked data from the HUNT Study, Medical Birth Registry of Norway, validated hospital records, and Norwegian Cause of Death Registry. Using an established CVD risk prediction model (NORRISK 2), we predicted 10-year risk of CVD (non-fatal myocardial infarction, fatal coronary heart disease, and non-fatal or fatal stroke) based on established risk factors (age, systolic blood pressure, total and HDL-cholesterol, smoking, anti-hypertensives, and family history of myocardial infarction). We evaluated whether adding pregnancy complication history improved model fit, calibration, discrimination, and reclassification. Among 18 231 women who were parous, ≥40 years of age, and CVD-free at start of follow-up, 39% had any pregnancy complication history and 5% experienced a CVD event during a median follow-up of 8.2 years. While pre-eclampsia and SGA were associated with CVD in unadjusted models (HR 1.96, 95% CI 1.44-2.65 for pre-eclampsia and HR 1.46, 95% CI 1.18-1.81 for SGA), only pre-eclampsia remained associated with CVD after adjusting for established risk factors (HR 1.60, 95% CI 1.16-2.17). Adding pregnancy complication history to the established prediction model led to small improvements in discrimination (C-index difference 0.004, 95% CI 0.002-0.006) and reclassification (net reclassification improvement 0.02, 95% CI 0.002-0.05).

Conclusion: Pre-eclampsia independently predicted CVD after controlling for established risk factors; however, adding pre-eclampsia, gestational hypertension, preterm delivery, and SGA made only small improvements to CVD prediction among this representative sample of parous Norwegian women.
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http://dx.doi.org/10.1093/eurheartj/ehy863DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6451770PMC
April 2019

Life Course Trajectories of Cardiovascular Risk Factors in Women With and Without Hypertensive Disorders in First Pregnancy: The HUNT Study in Norway.

J Am Heart Assoc 2018 08;7(15):e009250

1 Department of Public Health and Nursing NTNU Norwegian University of Science and Technology Trondheim Norway.

Background Women with hypertensive pregnancy disorders have adverse levels of cardiovascular risk factors. It is unclear how this adverse risk factor profile evolves during adult life. We compared life course trajectories of cardiovascular risk factors in women with preeclampsia or gestational hypertension in their first pregnancy to normotensive women. Methods and Results We linked information on cardiovascular risk factors from the population-based HUNT (Nord-Trøndelag Health Study) surveys with pregnancy information from the Medical Birth Registry of Norway. Trajectories of cardiovascular risk factors were constructed for 22 308 women with a normotensive first pregnancy; 1092 with preeclampsia, and 478 with gestational hypertension in first pregnancy. Already before first pregnancy, women with preeclampsia in their first pregnancy had higher measures of adiposity, blood pressure, heart rate, and serum lipids and glucose compared with women with a normotensive first pregnancy. After first pregnancy, there was a parallel development in cardiovascular risk factor levels, but women with a normotensive first pregnancy had a time lag of >10 years compared with the preeclampsia group. There were no clear differences in risk factor trajectories between women with gestational hypertension and women with preeclampsia. Conclusions Women with hypertensive pregnancy disorders in their first pregnancy had an adverse cardiovascular risk factor profile before pregnancy compared with normotensive women, and the differences persisted beyond 50 years of age. Hypertensive disorders in pregnancy signal long-term increases in modifiable cardiovascular risk factors, and may be used to identify women who would benefit from early prevention strategies.
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http://dx.doi.org/10.1161/JAHA.118.009250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6201453PMC
August 2018

Does pregnancy alter life-course lipid trajectories? Evidence from the HUNT Study in Norway.

J Lipid Res 2018 12 12;59(12):2403-2412. Epub 2018 Oct 12.

Department of Epidemiology Harvard T.H. Chan School of Public Health, Boston, MA.

We examined the association between pregnancy and life-course lipid trajectories. Linked data from the Nord-Trøndelag Health Study and the Medical Birth Registry of Norway yielded 19,987 parous and 1,625 nulliparous women. Using mixed-effects spline models, we estimated differences in nonfasting lipid levels from before to after first birth in parous women and between parous and nulliparous women. HDL cholesterol (HDL-C) dropped by -4.2 mg/dl (95% CI: -5.0, -3.3) from before to after first birth in adjusted models, a 7% change, and the total cholesterol (TC) to HDL-C ratio increased by 0.18 (95% CI: 0.11, 0.25), with no change in non-HDL-C or triglycerides. Changes in HDL-C and the TC/HDL-C ratio associated with pregnancy persisted for decades, leading to altered life-course lipid trajectories. For example, parous women had a lower HDL-C than nulliparous women at the age of 50 years (-1.4 mg/dl; 95% CI: -2.3, -0.4). Adverse changes in lipids were greatest after first birth, with small changes after subsequent births, and were larger in women who did not breastfeed. Findings suggest that pregnancy is associated with long-lasting adverse changes in HDL-C, potentially setting parous women on a more atherogenic trajectory than prior to pregnancy.
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http://dx.doi.org/10.1194/jlr.P085720DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6277164PMC
December 2018

Alterations in the vitamin D endocrine system during pregnancy: A longitudinal study of 855 healthy Norwegian women.

PLoS One 2018 11;13(4):e0195041. Epub 2018 Apr 11.

Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.

To ensure optimal calcium accrual in the fetal skeleton, a substantial rise occurs in 1,25-dihydroxyvitamin D (1,25(OH)2D), but is dependent on sufficient 25-hydroxyvitamin (25(OH)D). Large longitudinal studies addressing free 25(OH)D and 1,25(OH)2D during pregnancy are scarce. We aimed to assess levels of and relationship between 25(OH)D, 1,25(OH)2D, vitamin D-binding protein (DBP), parathyroid hormone (PTH), and free 25(OH)D during pregnancy; determinants of vitamin D status; and association between vitamin D indices or PTH and pregnancy outcomes (gestational diabetes mellitus and birthweight). Altogether 855 pregnant Norwegian Caucasian women from Trondheim and Stavanger (latitude 63°N and 58°N) were recruited; 94 were lost to follow-up. The study was originally a randomized controlled trial (2007-2009) with gestational diabetes as primary outcome. Data were collected in second and third trimester. In third trimester, 246 (34%) had vitamin D insufficiency and 52 (7%) deficiency (25(OH)D <50 and <30nmol/L, respectively). During wintertime in third trimester, 61 (47%) from Trondheim and 23 (51%) from Stavanger exhibited vitamin D insufficiency. PTH was elevated in 27 (3.7%). Estimate of change between trimesters was (95% CI): 25(OH)D -1.8 (-2.8 to -0.7) nmol/L, DBP 0.62 (0.57 to 0.66) μmol/L, calculated free 25(OH)D -1.7 (-2.0 to -1.4) pmol/L, PTH 0.81 (0.72 to 0.90) pmol/L, 1,25(OH)2D (sub-analysis) 31.4 (CI 24.7 to 38.2) pmol/L. A decrease in 1,25(OH)2D occurred in 45% of those with vitamin D deficiency, and they also exhibited lower levels than women with adequate vitamin D status. No association of vitamin D indices and PTH with pregnancy outcomes was observed. Women in Trondheim displayed lower 25(OH)D levels, despite minor latitudinal differences. Less than one-fifth adhered to the authorities' vitamin D recommendations. These findings demonstrate that hypovitaminosis D is prevalent among pregnant women living in northern latitudes, especially during the dark season, and there is an unmet need to ensure adequate vitamin D intake.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0195041PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5895009PMC
July 2018

Is smoking heaviness causally associated with alcohol use? A Mendelian randomization study in four European cohorts.

Int J Epidemiol 2018 08;47(4):1098-1105

MRC Integrative Epidemiology Unit (IEU), University of Bristol, Bristol, UK.

Background: Observational studies have shown that tobacco and alcohol use co-occur, but it is not clear whether this relationship is causal.

Methods: Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC) and UK Biobank, we used observational methods to test the hypothesis that smoking heaviness increases alcohol consumption. Mendelian randomization (MR) analyses were then used to test the causal relationship between smoking heaviness and alcohol consumption using 55 967 smokers from four European studies [ALSPAC, The Nord-Trøndelag Health Study (HUNT), the Copenhagen General Population Study (CGPS) and UK Biobank]. MR analyses used rs1051730/rs16969968 as a genetic proxy for smoking heaviness.

Results: Observational results provided evidence of an association between cigarettes per day and weekly alcohol consumption (increase in units of alcohol per additional cigarette smoked per day = 0.10, 95% confidence interval (CI) 0.05 to 0.15, P ≤ 0.001 in ALSPAC; and 0.48, 95% CI 0.45 to 0.52, P ≤ 0.001 in UK Biobank). However, there was little evidence for an association between rs1051730/rs16969968 and units of alcohol consumed per week across ALSPAC, HUNT, CGPS and UK Biobank (standard deviation increase in units of alcohol per additional copy of the risk allele = -0.004, 95% CI -0.023 to 0.016, P=0.708, I2 = 51.9%). We had 99% and 88% power to detect a change of 0.03 and 0.02 standard deviation units of alcohol per additional copy of the risk allele, respectively.

Conclusions: Previously reported associations between smoking and alcohol are unlikely to be causal, and may be the result of confounding and/or reverse causation. This has implications for public health research and intervention research.
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http://dx.doi.org/10.1093/ije/dyy027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6124618PMC
August 2018

Serum 25-hydroxyvitamin D, vitamin D supplement and asthma control: The HUNT study.

Respir Med 2018 03 31;136:65-70. Epub 2018 Jan 31.

Department of Public Health and General Practice, Faculty of Medicine, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.

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.
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http://dx.doi.org/10.1016/j.rmed.2018.01.017DOI Listing
March 2018

White Blood Cell BRCA1 Promoter Methylation Status and Ovarian Cancer Risk.

Ann Intern Med 2018 03 16;168(5):326-334. Epub 2018 Jan 16.

University of Bergen and Haukeland University Hospital, Bergen, Norway (P.E.L., E.O.B., L.M., R.C., S.B., C.E., L.B., H.B.S., S.K.).

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.
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http://dx.doi.org/10.7326/M17-0101DOI Listing
March 2018

Maternal Smoking in Pregnancy and Offspring Depression: a cross cohort and negative control study.

Sci Rep 2017 10 3;7(1):12579. Epub 2017 Oct 3.

MRC Integrative Epidemiology Unit (IEU) at the University of Bristol, Bristol, United Kingdom.

Previous reports suggest that offspring of mothers who smoke during pregnancy have greater risk of developing depression. However, it is unclear whether this is due to intrauterine effects. Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC) from the UK (N = 2,869), the Nord-Trøndelag health study (HUNT) from Norway (N = 15,493), the Pelotas 1982 Birth Cohort Study from Brazil (N = 2,626), and the Swedish Sibling Health Cohort (N = 258 sibling pairs), we compared associations of maternal smoking during pregnancy and mother's partner's smoking during pregnancy with offspring depression and performed a discordant sibling analysis. In meta-analysis, maternal smoking during pregnancy was associated with higher odds of offspring depression (OR 1.20, 95% CI:1.08,1.34), but mother's partner's smoking during pregnancy was not (OR 1.05, 95% CI:0.94,1.17). However, there was only weak statistical evidence that the odds ratios for maternal and mother's partner's smoking differed from each other (p = 0.08). There was no clear evidence for an association between maternal smoking during pregnancy and offspring depression in the sibling analysis. Findings do not provide strong support for a causal role of maternal smoking during pregnancy in offspring depression, rather observed associations may reflect residual confounding relating to characteristics of parents who smoke.
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http://dx.doi.org/10.1038/s41598-017-11836-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5626710PMC
October 2017

Obesity, Waist Circumference, Weight Change, and Risk of Incident Psoriasis: Prospective Data from the HUNT Study.

J Invest Dermatol 2017 12 2;137(12):2484-2490. Epub 2017 Aug 2.

Department of Dermatology, St. Olavs Hospital, Trondheim University Hospital, Norway; Department of Cancer Research and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway.

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.
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http://dx.doi.org/10.1016/j.jid.2017.07.822DOI Listing
December 2017

Pre-pregnancy Blood Pressure and Offspring Sex in the HUNT Study, Norway.

Am J Hypertens 2017 09;30(9):e7-e8

Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.

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http://dx.doi.org/10.1093/ajh/hpx100DOI Listing
September 2017

Investigating the causal effect of smoking on hay fever and asthma: a Mendelian randomization meta-analysis in the CARTA consortium.

Sci Rep 2017 05 22;7(1):2224. Epub 2017 May 22.

Copenhagen Prospective Studies on Asthma in Childhood (COPSAC), Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.

Observational studies on smoking and risk of hay fever and asthma have shown inconsistent results. However, observational studies may be biased by confounding and reverse causation. Mendelian randomization uses genetic variants as markers of exposures to examine causal effects. We examined the causal effect of smoking on hay fever and asthma by using the smoking-associated single nucleotide polymorphism (SNP) rs16969968/rs1051730. We included 231,020 participants from 22 population-based studies. Observational analyses showed that current vs never smokers had lower risk of hay fever (odds ratio (OR) = 0·68, 95% confidence interval (CI): 0·61, 0·76; P < 0·001) and allergic sensitization (OR = 0·74, 95% CI: 0·64, 0·86; P < 0·001), but similar asthma risk (OR = 1·00, 95% CI: 0·91, 1·09; P = 0·967). Mendelian randomization analyses in current smokers showed a slightly lower risk of hay fever (OR = 0·958, 95% CI: 0·920, 0·998; P = 0·041), a lower risk of allergic sensitization (OR = 0·92, 95% CI: 0·84, 1·02; P = 0·117), but higher risk of asthma (OR = 1·06, 95% CI: 1·01, 1·11; P = 0·020) per smoking-increasing allele. Our results suggest that smoking may be causally related to a higher risk of asthma and a slightly lower risk of hay fever. However, the adverse events associated with smoking limit its clinical significance.
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http://dx.doi.org/10.1038/s41598-017-01977-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5440386PMC
May 2017

Relationship between pubertal timing and chronic nonspecific pain in adolescent girls: the Young-HUNT3 study (2006-2008).

Pain 2017 08;158(8):1554-1560

Department of Laboratory Medicine, Children's and Women's Health, Faculty of Medicine and Health Sciences, NTNU - Norwegian University of Science and Technology, Trondheim, Norway.

The aim of this study was to examine a possible relationship between early puberty and chronic nonspecific pain in 13- to 18-year-old girls. All adolescents in Nord-Trøndelag County, Norway, were invited to participate in the Young-HUNT3 study (2006-2008). Of the invited girls, 81% answered the questionnaire and of these 3982 were 13 to 18 years of age. Menarche and perceived physical maturation were used as exposure measures. Early menarche was defined as <12 years, normal menarche as ≥12 and <14 years, and late menarche as ≥14 years. Perceived physical maturation was divided into maturing earlier, the same or later than others of their own age. The main outcome measure was chronic nonspecific pain, defined as pain in at least one location not related to any known disease or injury, for at least once a week during the last 3 months. The median age at menarche was 13.2 years. Chronic nonspecific pain was more prevalent among girls with early menarche (68%, 95% CI: 64%-72%) compared to girls with either normal (55%, 95% CI: 53%-57%), late (50%, 95% CI: 46%-54%), or no menarche (35%, 95% CI: 29%-40%). The association persisted after adjusting for age, body mass index, socioeconomic factors, and anxiety and depression. A similar association was found between girls that perceived themselves as earlier physically matured than their peers and chronic nonspecific pain. Headache/migraine was the most common type of chronic nonspecific pain regardless of menarcheal age. In all reported locations, pain was more prevalent in the group with early menarche compared to normal or late menarche.
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http://dx.doi.org/10.1097/j.pain.0000000000000950DOI Listing
August 2017

Cancer cachexia associates with a systemic autophagy-inducing activity mimicked by cancer cell-derived IL-6 trans-signaling.

Sci Rep 2017 05 17;7(1):2046. Epub 2017 May 17.

Department of Medical Laboratory Technology, Faculty of Natural Sciences, NTNU - Norwegian University of Science and Technology, 7491, Trondheim, Norway.

The majority of cancer patients with advanced disease experience weight loss, including loss of lean body mass. Severe weight loss is characteristic for cancer cachexia, a condition that significantly impairs functional status and survival. The underlying causes of cachexia are incompletely understood, and currently no therapeutic approach can completely reverse the condition. Autophagy coordinates lysosomal destruction of cytosolic constituents and is systemically induced by starvation. We hypothesized that starvation-mimicking signaling compounds secreted from tumor cells may cause a systemic acceleration of autophagy during cachexia. We found that IL-6 secreted by tumor cells accelerates autophagy in myotubes when complexed with soluble IL-6 receptor (trans-signaling). In lung cancer patients, were cachexia is prevalent, there was a significant correlation between elevated IL-6 expression in the tumor and poor prognosis of the patients. We found evidence for an autophagy-inducing bioactivity in serum from cancer patients and that this is clearly associated with weight loss. Importantly, the autophagy-inducing bioactivity was reduced by interference with IL-6 trans-signaling. Together, our findings suggest that IL-6 trans-signaling may be targeted in cancer cachexia.
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http://dx.doi.org/10.1038/s41598-017-02088-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5435723PMC
May 2017

Sonographic prediction of outcome of vacuum deliveries: a multicenter, prospective cohort study.

Am J Obstet Gynecol 2017 07 19;217(1):69.e1-69.e10. Epub 2017 Mar 19.

National Center for Fetal Medicine, Trondheim University Hospital (St Olav's Hospital) and Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology, Trondheim, Norway.

Background: Safe management of the second stage of labor is of great importance. Unnecessary interventions should be avoided and correct timing of interventions should be focused. Ultrasound assessment of fetal position and station has a potential to improve the precision in diagnosing and managing prolonged or arrested labors. The decision to perform vacuum delivery is traditionally based on subjective assessment by digital vaginal examination and clinical expertise and there is currently no method of objectively quantifying the likelihood of successful delivery. Prolonged attempts at vacuum delivery are associated with neonatal morbidity and maternal trauma, especially so if the procedure is unsuccessful and a cesarean is performed.

Objective: The aim of the study was to assess if ultrasound measurements of fetal position and station can predict duration of vacuum extractions, mode of delivery, and fetal outcome in nulliparous women with prolonged second stage of labor.

Study Design: We performed a prospective cohort study in nulliparous women at term with prolonged second stage of labor in 7 European maternity units from 2013 through 2016. Fetal head position and station were determined using transabdominal and transperineal ultrasound, respectively. Our preliminary clinical experience assessing head-perineum distance prior to vacuum delivery suggested that we should set 25 mm for the power calculation, a level corresponding roughly to +2 below the ischial spines. The main outcome was duration of vacuum extraction in relation to ultrasound measured head-perineum distance with a predefined cut-off of 25 mm, and 220 women were needed to discriminate between groups using a hazard ratio of 1.5 with 80% power and alpha 5%. Secondary outcomes were delivery mode and umbilical artery cord blood samples after birth. The time interval was evaluated using survival analyses, and the outcomes of delivery were evaluated using receiver operating characteristic curves and descriptive statistics. Results were analyzed according to intention to treat.

Results: The study population comprised 222 women. The duration of vacuum extraction was shorter in women with head-perineum distance ≤25 mm (log rank test <0.01). The estimated median duration in women with head-perineum distance ≤25 mm was 6.0 (95% confidence interval, 5.2-6.8) minutes vs 8.0 (95% confidence interval, 7.1-8.9) minutes in women with head-perineum distance >25 mm. The head-perineum distance was associated with spontaneous delivery with area under the curve 83% (95% confidence interval, 77-89%) and associated with cesarean with area under the curve 83% (95% confidence interval, 74-92%). In women with head-perineum distance ≤35 mm, 7/181 (3.9%) were delivered by cesarean vs 9/41 (22.0%) in women with head-perineum distance >35 mm (P <.01). Ultrasound-assessed position was occiput anterior in 73%. Only 3/138 (2.2%) fetuses in occiput anterior position and head-perineum distance ≤35 mm vs 6/17 (35.3%) with nonocciput anterior position and head-perineum distance >35 mm were delivered by cesarean. Umbilical cord arterial pH <7.10 occurred in 2/144 (1.4%) women with head-perineum distance ≤35 mm compared to 8/40 (20.0%) with head-perineum distance >35 mm (P < .01).

Conclusion: Ultrasound has the potential to predict labor outcome in women with prolonged second stage of labor. The information obtained could guide whether vacuum delivery should be attempted or if cesarean is preferable, whether senior staff should be in attendance, and if the vacuum attempt should be performed in the operating theater.
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http://dx.doi.org/10.1016/j.ajog.2017.03.009DOI Listing
July 2017

Hypertension in Pregnancy and Offspring Cardiovascular Risk in Young Adulthood: Prospective and Sibling Studies in the HUNT Study (Nord-Trøndelag Health Study) in Norway.

Hypertension 2017 04 21;69(4):591-598. Epub 2017 Feb 21.

From the Department of Public Health and General Practice, Faculty of Medicine, NTNU, Norwegian University of Science and Technology, Trondheim (I.V.A., L.J.V., J.H.B., J.R.-E., P.R.R., B.O.Å.); MRC Integrative Epidemiology Unit at the University of Bristol and School of Social and Community Medicine, University of Bristol, United Kingdom (A.F.); Channing Division of Network Medicine, Department of Medicine, Connors Center for Women's Health and Gender Biology, Brigham and Women's Hospital, Boston, MA (J.R.-E.); Harvard Medical School, Boston, MA (J.R.-E.); Department of Epidemiology, the Harvard T.H. Chan School of Public Health, Boston, MA (L.J.V., J.R.-E.); and Department of Endocrinology, St. Olavs Hospital, Trondheim University Hospital, Norway (B.O.Å.).

Women with hypertensive disorders in pregnancy are at increased lifetime risk for cardiovascular disease. We examined the offspring's cardiovascular risk profile in young adulthood and their siblings' cardiovascular risk profile. From the HUNT study (Nord-Trøndelag Health Study) in Norway, 15 778 participants (mean age: 29 years), including 210 sibling groups, were linked to information from the Medical Birth Registry of Norway. Blood pressure, anthropometry, serum lipids, and C-reactive protein were assessed. Seven hundred and six participants were born after exposure to maternal hypertension in pregnancy: 336 mothers had gestational hypertension, 343 had term preeclampsia, and 27 had preterm preeclampsia. Offspring whose mothers had hypertension in pregnancy had 2.7 (95% confidence interval, 1.8-3.5) mm Hg higher systolic blood pressure, 1.5 (0.9-2.1) mm Hg higher diastolic blood pressure, 0.66 (0.31-1.01) kg/m higher body mass index, and 1.49 (0.65-2.33) cm wider waist circumference, compared with offspring of normotensive pregnancies. Similar differences were observed for gestational hypertension and term preeclampsia. Term preeclampsia was also associated with higher concentrations of non-high-density lipoprotein cholesterol (0.14 mmol/L, 0.03-0.25) and triglycerides (0.13 mmol/L, 0.06-0.21). Siblings born after a normotensive pregnancy had nearly identical risk factor levels as siblings born after maternal hypertension. Offspring born after maternal hypertension in pregnancy have a more adverse cardiovascular risk profile in young adulthood than offspring of normotensive pregnancies. Their siblings, born after a normotensive pregnancy, have a similar risk profile, suggesting that shared genes or lifestyle may account for the association, rather than an intrauterine effect. All children of mothers who have experienced hypertension in pregnancy may be at increased lifetime risk of cardiovascular disease.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.116.08414DOI Listing
April 2017

Cardiovascular mortality - Comparing risk factor associations within couples and in the total population - The HUNT Study.

Int J Cardiol 2017 Apr 6;232:127-133. Epub 2017 Jan 6.

Department of Public Health, Faculty of Medicine, Norwegian University of Science and Technology, 7491 Trondheim, Norway; Regional Center for Health Care Improvement, St Olav Hospital, Trondheim, Norway.

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 20mmHg), 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 10mmHg), 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.
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http://dx.doi.org/10.1016/j.ijcard.2017.01.041DOI Listing
April 2017

Premature Adult Death in Individuals Born Preterm: A Sibling Comparison in a Prospective Nationwide Follow-Up Study.

PLoS One 2016 7;11(11):e0165051. Epub 2016 Nov 7.

Institute of Public Health and General Practice, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.

Background: Close to one in ten individuals worldwide is born preterm, and it is important to understand patterns of long-term health and mortality in this group. This study assesses the relationship between gestational age at birth and early adult mortality both in a nationwide population and within sibships. The study adds to existing knowledge by addressing selected causes of death and by assessing the role of genetic and environmental factors shared by siblings.

Methods: Study population was all Norwegian men and women born from 1967 to 1997 followed using nation-wide registry linkage for mortality through 2011 when they were between 15 and 45 years of age. Analyses were performed within maternal sibships to reduce variation in unobserved genetic and environmental factors shared by siblings. Specific outcomes were all-cause mortality and mortality from cardiovascular diseases, cancer and external causes including accidents, suicides and drug abuse/overdoses.

Results: Compared with a sibling born in week 37-41, preterm siblings born before 34 weeks gestation had 50% increased mortality from all causes (adjusted Hazard Ratio (aHR) 1.54, 95% confidence interval (CI) 1.17, 2.03). The corresponding estimate for the entire population was 1.27 (95% CI 1.09, 1.47). The majority of deaths (65%) were from external causes and the corresponding risk estimates for these deaths were 1.52 (95% CI 1.08, 2.14) in the sibships and 1.20 (95% CI 1.01, 1.43) in the population.

Conclusion: Preterm birth before week 34 was associated with increased mortality between 15 and 45 years of age. The results suggest that increased premature adult mortality in this group is related to external causes of death and that the increased risks are unlikely to be explained by factors shared by siblings.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0165051PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5098830PMC
September 2017

Colposcopy and additive diagnostic value of biopsies from colposcopy-negative areas to detect cervical dysplasia.

Acta Obstet Gynecol Scand 2016 Nov;95(11):1258-1263

Department of Public Health and General Practice, Norwegian University of Science and Technology, Trondheim, Norway.

Introduction: We evaluated colposcopy in the routine diagnostic workup of women with abnormal cervical cytology, as well as the diagnostic value of endocervical curettage material and biopsies taken from colposcopy-positive and colposcopy-negative quadrants of the cervix.

Material And Methods: This cross-sectional study included 297 nonpregnant women with abnormal cervical cytology and no prior treatment for cervical dysplasia or cancer. All women underwent gynecological examination, colposcopy, endocervical curettage, and had cervical biopsies taken. Colposcopy was considered satisfactory if the squamocolumnar junction was fully visible, and biopsies were taken from all four quadrants of the cervix, regardless of colposcopy results.

Results: In all, 130 of the women in our study had satisfactory colposcopy results and were diagnosed with cervical intraepithelial neoplasia grade 2 or worse (CIN2+), 61% via a colposcopy-positive biopsy and 39% via a colposcopy-negative biopsy. Eighty-seven of them had positive colposcopy results, but CIN2+ was histologically verified from colposcopy-positive biopsies in 91% (n = 79) and from colposcopy-negative biopsies in 9% (n = 8). The remaining 43 women with CIN2+ had negative colposcopy findings, so their diagnosis was verified in colposcopy-negative biopsies. The sensitivity of colposcopy alone to detect CIN2+ was 61% (95% CI 52-69).

Conclusions: In the present study, colposcopy was not a stand-alone diagnostic method. Colposcopy-negative biopsies had a clear additive value, identifying a substantial proportion of women with both positive and negative colposcopy results with treatment-worthy cervical dysplasia. Endocervical curettage material had little diagnostic value in this study.
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http://dx.doi.org/10.1111/aogs.13009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5129518PMC
November 2016

Duration of the active phase of labor in spontaneous and induced labors.

Acta Obstet Gynecol Scand 2017 Jan 9;96(1):120-127. Epub 2016 Nov 9.

Department of Obstetrics and Gynecology, Stavanger University Hospital, Stavanger, Norway.

Introduction: The aim of the study was to compare the duration of active phase of labor in women with spontaneous or induced start of labor.

Material And Methods: An observational cohort study was performed at Stavanger University Hospital in Norway between January 2010 and December 2013. During the study period 19 524 women delivered. Data for the study were collected from an electronic birth journal. Women with previous cesarean section, multiple pregnancy, breech or transverse lie, preterm labor or prelabor cesarean section were excluded. Analyses were stratified between nulliparous and parous women. Active phase of labor was defined when contractions were regular, with cervix effaced and dilated 4 cm. The main outcome measure was duration of active phase of labor.

Results: The active phase was longer in induced labors than in labors with spontaneous onset in nulliparous women. The estimated median duration using survival analyses was 433 min (95% confidence interval 419-446) in spontaneous vs. 541 min (95% confidence interval 502-580) in induced labors [unadjusted hazard ratio 0.76 (95% confidence interval 0.71-0.82) and adjusted hazard ratio 0.88 (95% confidence interval 0.82-0.95)]. In parous women, a one minus survival plot showed that induced labors had shorter duration before six hours in active labor, but after six hours, induced labors had longer duration. The overall difference in parous women was small and probably of little clinical importance.

Conclusion: The active phase of labor was longer in induced than in spontaneous labors in nulliparous women.
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http://dx.doi.org/10.1111/aogs.13039DOI Listing
January 2017

Physical activity and lung function decline in adults with asthma: The HUNT Study.

Respirology 2017 02 2;22(2):278-283. Epub 2016 Oct 2.

Faculty of Medicine, Department of Public Health and General Practice, Norwegian University of Science and Technology, Trondheim, Norway.

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 (FEV ) 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 FEV /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 FEV , FEV /FVC ratio and PEF.
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http://dx.doi.org/10.1111/resp.12884DOI Listing
February 2017

Self-reported Chronic Pain in Young Adults With a Low Birth Weight.

Clin J Pain 2017 04;33(4):348-355

Departments of *Laboratory Medicine, Children's and Women's Health §Public Health and General Practice, Faculty of Medicine †Regional Centre for Child and Youth Mental Health and Child Welfare, Norwegian University of Science and Technology ‡Department of Child and Adolescent Psychiatry, St. Olavs Hospital, Trondheim University Hospital ∥Department of Physiotherapy, Trondheim Municipality ¶Department of Pediatrics, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.

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.
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http://dx.doi.org/10.1097/AJP.0000000000000399DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5348108PMC
April 2017

Health care contact following a new incident neck or low back pain episode in the general population; the HUNT study.

BMC Health Serv Res 2016 Mar 8;16:81. Epub 2016 Mar 8.

Department of Public Health and General Practice, Faculty of Medicine, Norwegian University of Science and Technology, Medisinsk teknisk forskningssenter, P.O. Box 8905, Trondheim, 7491, Norway.

Background: Low back and neck pain are commonly reported in the general population and represent frequent causes for health care consultations. The main aim of this study was to describe the determinants of health care contact during a 1-year period in a general population with recent onset spinal pain.

Methods: From 9056 participants in a general health survey in Norway we identified 219 persons reporting a recent onset (<1 month) of low back or neck pain. Questionnaires were given at 1 (baseline), 2, 3, 6 and 12 months after pain debut. The main outcome was self-reported health care contact due to spinal pain. Associations between health care contact and pain-related factors, other somatic and mental health factors, pain-related work limitations, physical activity and sociodemographic factors were explored.

Results: Conventional health care was sought by 93 persons (43 %) at least once throughout the year following the onset of pain. 18 persons (8 %) sought alternative health care only and 108 persons (49 %) sought no kind of health care. Baseline reports of coexisting low back and neck pain of equal intensity, poor self-reported health, symptoms of anxiety or depression, obesity and smoking were all associated with an increased tendency to seek conventional health care. Pain intensity and pain-related work limitations at each occasion were strongly associated with concurrent health care contact throughout the year. Higher education was associated with a reduced tendency to contact health care and no association was found for physical activity.

Conclusion: The main finding in this study was that people from the general population who seek health-care for a new incident of neck or low back pain report more symptoms of mental distress, poorer self-reported health and more intense pain with stronger work limitations compared to those who do not. The findings suggest that identification of complementary symptoms is highly relevant in the examination of spinal pain patients, even for those with recent onset of symptoms.
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http://dx.doi.org/10.1186/s12913-016-1326-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4782331PMC
March 2016