Prosjektkatalog Kvinners helse Oppdatert per 17.2.2011
INNHOLD Pågående prosjekter...3 Prosjekt 205400 Mechanisms for vascular disease in women - Inflammation in pre-eclampsia and atherosclerosis.. 3 Prosjekt 191098 Fear of childbirth: causes and consequences... 4 Prosjekt 190398 Risk factors and pregnancy outcomes of hyperemesis gravidarum (HG)... 5 Prosjekt 185755 VIOLENCE AGAINST WOMEN-A public health problem. Prospective populationsbased cohortstudies on general and reproductive health... 6 Avsluttede prosjekter...7 Prosjekt 186031 Mothers of children with congenital heart disease (CHD): psychosocial problems from pregnancy through child age 3 years... 7 Prosjekt 181809 Energy Balance and Breast Cancer Aspects. A randomised clinical trial with physical activity interventions... 8 Prosjekt 178588 Effects of Pregnancy, Lactation and Menopause on Bone Health... 9 Prosjekt 175326 Sosial ulikhet I kvinners helse belyst med helseundersøkelsen I Nord- Trøndelag (HUNT)... 10 Prosjekt 175329 Is osteoporosis related to the risk of atherosclerosis and cardiovascular disease?... 11 Prosjekt 166154 Norwegian Epidemiological Osteoporosis Studies. Why does the risk of osteoporotic fractures vary within Norway?... 12 Prosjekt 160372 Primær og sekundær osteoporose (OP) studert ved hjelp av genekspresjonsprofilering i ben... 13 Prosjekt 160369 Anorektisk helsetjeneste: En serie brukerbaserte studier av helsetjeneste karriere og behandlingstilbud til kvinner med alvorlige spiseforstyrrelser... 14 Prosjekt 160739 Enogent cushing syndrom og steroid indusert osteoporose: Studier på molekylært grunnlag for patofysiologiske forandringer i benmetabolismen... 15 2
Pågående prosjekter Prosjekt 205400 Mechanisms for vascular disease in women - Inflammation in pre-eclampsia and atherosclerosis Prosjektansvarlig: NTNU Prosjektleder: Ann-Charlotte Iversen Prosjektperiode: 2011-2013 Budsjett: 5,1 mill kr Program/fagkomite: Fagkomiteen for klinisk medisin og folkehelse Pre-eclampsia (PE) is a major cause of maternal disease/death in pregnancy and affects about 5% of pregnant women. In severe cases, PE may also involve the fetus, causing premature deliveries and fetal growth restriction. Enhanced systemic inflammation and vascular endothelial activation are characteristic findings in pre-eclamptic women. Similar hallmarks are found in cardiovascular disease (CVD), and in accordance with this; women with previous pre-eclamptic pregnancies, have doubled risk for later-life CVD. In many ways pregnancy may be considered a metabolic stress test, and thus, PE may be the first clinical manifestation suggesting that an apparently healthy young woman in fact houses abnormal metabolic/inflammatory responses. In this project, mechanisms underlying PE and CVD will be explored by focusing on inflammation.both initiating signals (endogenous damage/danger signals and pathogen components) and receptivity (pattern recognition receptors (PRRs)) of cases/controls will be assessed. The genetic influence will be assessed by genotyping PRR-related genes in women with/without PE and with/without CVD in several large Norwegian cohorts. In addition, levels of inflammatory signals and activation will be compared. The role of local inflammatory responses at the maternal-fetal site will be studied in placental/decidual tissues and in vitro studies of fetal trophoblasts. In the present project, the aim is to study, and compare, inflammatory mechanisms associated with both PE and CVD in women. Findings may potentially open for tests for risk assessment, useful for a maternity care aiming to increase attention to pregnant women at risk. In addition, findings may potentially open for new therapeutic approaches. Development of CVD appears to have gender-specific mechanisms, which remain to be elucidated. Knowledge gained from the combined study of PE and CVD may generate useful insight in mechanisms underlying the female way of developing CVD. 3
Prosjekt 191098 Fear of childbirth: causes and consequences Prosjektansvarlig: Akershus Universitetssykehus HF Prosjektleder: Malin Eberhard-Gran Prosjektperiode: 2009 2012 Budsjett: 6,6 mill kr Program/fagkomite: Fagkomiteen for klinisk medisin og folkehelse The Western world has an epidemic of self perceived fear of childbirth. Between 5 and 10% of all pregnant women in the Oslo area are being treated for fear of childbirth. Steadily increasing numbers of pregnant women are requesting caesarean sections due to fear of giving birth. However, caesarean deliveries are associated with increased risk of maternal complication and increased use of hospital resources. Little is known of the causes of the fear of childbirth. Also the relationship between fear of childbirth and criteria-based psychiatric anxiety disorders remains to be elucidated. In a prospective study, we intend to study 1) risk factors for self perceived fear of childbirth, 2) whether fear of childbirth affects the delivery or the child. The target population is all women giving birth at the Department of Obstetrics, Akershus University Hospital in the period 2008-09 (n = 3500-4000 women). Data will be collected using three questionnaires to the women at pregnancy weeks 17 and 34 and 6 weeks after delivery. The questionnaires include several mental health measures such as the Wijma Delivery Expectancy/ Experience Questionnaire, the Edinburgh Postnatal Depression Scale, the Hopkins Symptom Check List, the Anxiety Disorder Questionnaire, Kendlers Life Time Depression Scale, the Impact of Event Scale and the Internal-External Locus of Control Scale. Standardized questions about expectations and feelings associated with childbirth are also included. Data on delivery and pregnancy outcomes will be obtained through linkage to the electronic patient s records at the Department of Obstetrics (PARTUS). This will be the largest study, yet, addressing risk factors and consequences of fear of childbirth. The combination of a wide range of mental health measures with detailed obstetrical outcome variables makes this study unique. In order to improve the pre- and postnatal care, more knowledge on fear of childbirth is necessary. 4
Prosjekt 190398 Risk factors and pregnancy outcomes of hyperemesis gravidarum (HG) Prosjektansvarlig: Nasjonalt folkehelseinstitutt, Divisjon for epidemiologi Prosjektleder: Per Magnus Prosjektperiode: 2009 2012 Budsjett: 3,5 mill kr Program/fagkomite: Program for folkehelse Hyperemesis Gravidarum (HG) is a potentially lethal disorder of early pregnancy where the pregnant women suffer from excessive nausea and vomiting, leading to weight loss and nutritional deficits. The causes are entirely unknown. It is important to test hypotheses on infections and dietary factors, because such factors are potential targets for preventive actions. In addition, understanding the genetic basis of the disorder is important for further basic medical research. On this background, we will utilize existing resources administered by the Norwegian Institute of Public Health such as the Medical Birth Registry, The Twin Panel and the Norwegian Mother and Child Cohort Study to address the research objectives. The relative risk of HG according to infection with Helicobacter Pylori will be studied with the use of a case-control study where the data collection has already been performed. The primary objective is to understand causes and consequences of Hyperemesis Gravidarum (HG) so that this serious disorder can be better prevented and treated. The secondary objectives are to: 1. Estimate the relative risk of HG according to infection with Helocobacter pylori. 2. Estimate the relative risk of HG according to dietary patterns before pregnancy 3. Estimate the fetal and maternal genetic variance in the causal structure of HG 4. Estimate the relative risks of adverse pregnancy outcomes according to presence or absence of HG in early pregnancy 5
Prosjekt 185755 VIOLENCE AGAINST WOMEN-A public health problem. Prospective populationsbased cohortstudies on general and reproductive health Prosjektansvarlig: Det medisinske fakultet, NTNU Prosjektleder: Berit Schei Prosjektperiode: 2008 2011 Budsjett: 4,0 mill kr Program/fagkomite: Program for folkehelse Violence against women has only recently been brought onto the agenda of public health. The first national study on violence against women in Norway showed that one in five women reported partner inflicted physical or sexual violence any time in their lives, 9 %, reported ever experiencing life threatening violence. Knowledge of the public health consequences of violence is limited. However, violence may substantially contribute to women's health burden. One of the main sources for public health research is the various epidemiological health surveys in Norway, which traditionally have not included information on violence. Subprojects related to violence have for the first time been accepted in two studies so far: The Oslo Health Study (2000-2001) and the Norwegian Mother and Child Cohort (1999 ongoing). These studies, which have collected information on history of violence, can now be linked to health registries as Medical Birth Registry and Norwegian Prescription Database, and thus yield the unique opportunity to study the relationships between violence and health indicators both in a cross-sectional and a longitudinal design. 6
Avsluttede prosjekter Prosjekt 186031 Mothers of children with congenital heart disease (CHD): psychosocial problems from pregnancy through child age 3 years Prosjektansvarlig: Nasjonalt folkehelseinstitutt Divisjon for psykisk helse Prosjektleder: Margarete E. Vollrath Prosjektperiode: 2008 2010 Budsjett: 5,8 mill kr Program/fagkomite: Program for psykisk helse Background: Mothers that are pregnant with, give birth to and take care of an infant with congenital heart disease (CHD) are at risk to develop serious psychological and social problems. Today, advanced surgery saves the life of ever more severely affected children with CHD. Yet, we know little about their later development and the challenges facing their mothers. The planned study is part of a larger research effort on the mental health of children with CHD and their families. The basic study (HEARTKID) examining the mental health and development of children with CHD has already started. The planned study focuses on the children's mothers. Objectives: 1. to screen mothers of infants with CHD from pregnancy through child age three for psychological and social problems; 2. to determine the influence of medical status and treatment and psychological risk factors in the mother and the child on maternal problems. Method: We will use a case-control design and link two data sources: 1. the nationwide CHDregistry at Rikshospitalet, Norway. 2. the Norwegian Mother and Child Cohort Study (MoBa) that follows 95 000 children from the fetal stage. Among these children, we expect to identify ca. 500-700 infants with CHD. The MoBa study includes information about maternal mental health and social situation at gestation weeks 17 and 34, and information on the child's mental health at age 6, 18, and 36 months. Comprehensive information on the CHD diagnosis and treatment is available from the CHD registry. Scientific importance: This will be the first population-based cohort study following mothers of children with CHD from pregnancy. The design, the early start during pregnancy, the length of the follow-up period, and the sheer size of the study are unique and allow a comprehensive description and analysis of the maternal psychosocial situation not previously seen. 7
Prosjekt 181809 Energy Balance and Breast Cancer Aspects. A randomised clinical trial with physical activity interventions Prosjektansvarlig: Kreftsenteret Ullevål Universitetssykehus Prosjektleder: Inger Thune Prosjektperiode: 2007 2010 Budsjett: 2,4 mill kr Program/fagkomite: Program for folkehelse Breast cancer requires intense and prolonged treatments often associated with significant side effects, also influencing their levels of physical activity after diagnosis. New evidence from large cohort studies supports a role of physical activity in reducing recurrence and improving survival. According to current conceptions of breast cancer etiology and progression of the disease, metabolic profiles and ovarian steroids play a potentially important role at every stage of the disease process from the initial transformation of cells to the progress of disease post diagnosis. Physical activity affects several of these specific biological processes involved. Energy Balance and Breast Cancer Aspects study will have a prospective two-arm randomized design comparing physical activity vs. control. Women newly diagnosed with breast cancer at the Ullevaal University Hospital, will be invited to participate. Eligible women will be randomised to an intervention group (physical active group) or a control group (standard care). A senior consultant in oncology will follow the patients throughout the study. We will use a modified intervention program. The intervention group will receive a detailed training program modified for them at start with 15 minutes x 3/week, increasing to 45 minutes per session for 12 month. Patients will wear an accelerometer for a week at baseline and follow-up visits to assess physical activity level objectively Measurements will be performed among the participating patients. Patients will be followed annually after 12 month for additional 5 years. If such a trial demonstrates that physical activity influence metabolic profile and are of importance for breast cancer recurrence, physical activity should be prescribed as an integral part of breast cancer therapy. 8
Prosjekt 178588 Effects of Pregnancy, Lactation and Menopause on Bone Health Institusjon: Institutt for samfunnsmedisin Universitetet i Tromsø Prosjektleder: Åshild Bjørnerem Prosjektperiode: 2007 2009 Budsjett: 2,9 mill kr Program/fagkomite: Fagkomiteen for klinisk medisin og folkehelse Fragility fractures are a common public health problem particularly in Scandinavia. The pathogenesis of bone fragility is multi-factorial. Two factors will be studied; the effect of pregnancy and menopause. Whether pregnancy and lactation result in bone loss is not clear, and if so, whether calcium supplementation prevents bone loss is uncertain. After menopause, bone loss accelerates, but the structural basis underlying this loss of bone and the hormonal factors that contribute are not known. Advances in non-invasive technology provide a measurement of the three dimensional architecture of bone and improves the sensitivity of fracture risk prediction. We will recruit pregnant and non-pregnant women from fertility clinics in Melbourne, and randomize the pregnant women to calcium supplementation or placebo in double blind fashion. To study the effects of menopause, twins discordant for menopause will be recruited from the Australian National Health and Medical Research Council Twin Registry. Tromsø Osteoporosis Study has longitudinal data on parity, menopausal status, sex hormones, forearm BMD and fractures, which makes is possible to study the long-term effects of parity on bone health, and the hormones relation to menopausal bone loss and fracture risk. 9
Prosjekt 175326 Sosial ulikhet I kvinners helse belyst med helseundersøkelsen I Nord- Trøndelag (HUNT). Prosjektansvarlig: Det medisinske fakultet Norges teknisk-naturvitenskapelige universitet Prosjektleder: Steinar Westin Prosjektperiode: 2006 2009 Budsjett: delfinansieres kr. 500 000 pr/3år Program/fagkomite: Program for folkehelse Sammendrag: Europeiske sammenlignende studier på 1990-tallet antydet at Norge har langt større sosiale gradienter i sykdom enn det har vært vanlig til å tro. De fleste studier om disse spørsmålene de siste årene er gjort på menn, eventuelt menn og kvinner samlet. Noen studier har benyttet utdanning, men ellers kan det se ut til at forskere har rygget tilbake for de metodemessige vansker som er forbundet med å klassifisere kvinner etter sosioøkonomisk status i befolkningsundersøkelser. Det gjelder også studier i HUNT. Det er derfor mulig at de lavere gradientene man ser hos kvinner delvis kan skyldes såkalt misklassifisering. I dette prosjektet vil vi problematisere kjønn som dimensjon, med en videre utvikling av kunnskap om sosial ulikhet og helse hos kvinner, basert på HUNT-databasen. Arbeidet vil dels bestå i et teoretisk og praktisk grunnlagsarbeid for å vurdere ulike inndelinger av kvinner etter sosioøkonomiske status, dels vil vi se på ulike helseutfall. Av særlig interesse vil det være å følge opp interessante funn i Krokstads doktoravhandling, der det er påvist at kvinner i øverste sosiale (EGP)-klasse har høyere sannsynlighet for å få uførepensjon enn den nest høyeste klassen. Hvis dette kan gjenfinnes i andre mål for helse, vil det være et brudd med vanlige forestillinger om denne gradienten, og reise nye spørsmål om årsaker og forebygging. Arbeidet sikter på internasjonal publisering som grunnlag for en medisinsk doktorgrad. 10
Prosjekt 175329 Is osteoporosis related to the risk of atherosclerosis and cardiovascular disease? Prosjektansvarlig: Institutt for samfunnsmedisin Universitetet i Tromsø Prosjektleder: Lone Jørgensen Prosjektperiode: 2006 2009 Budsjett: delfinansieres kr. 500 000 pr/3år Program/fagkomite: Program for folkehelse Cardiovascular disease (CVD) and osteoporosis are major causes of morbidity and mortality among elderly people. The two conditions have generally been considered unrelated. However, studies have indicated that arterial calcification is an active, organised, regulated process similar to bone mineralization. Thus, there may be links between bone metabolism and vascular calcification, but data based on large longitudinal studies are very sparse. In the Tromsø study, a large population-based study, bone mineral density (BMD) was measured in 5716 subjects at baseline in 1994/95 and 7 years later. The examination also included carotid ultrasonography and measurements of e.g., weight, blood pressure and non-fasting serum lipids. These data may enable us to examine whether subjects with osteoporosis are at risk developing atherosclerosis and visa versa. The main objective of this population-based study is to describe how osteoporosis and cardiovascular diseases are interrelated. Thus, we will examine whether subjects with low BMD, and subjects who loose bone rapidly at increased risk of stroke and myocardial infarction and whether the presence and type of carotid artery plaque (an non-invasive measure of generalized atherosclerosis) is related to the risk of future fractures. Furthermore, does the loss of bone minerals differ in subjects with hard carotid artery plaques and subjects with soft or no plaques? We will also investigate relationships between risk factors for cardiovascular diseases (e.g., blood pressure, lipid profile at baseline (1994/1995), high glycated hemoglobin and micro albuminuria) and BMD and fracture risk within the following 7 years. A related question is whether changes in BMD from baseline to 2001 are related to changes in risk these factors. The study may identify subjects at increased risk of both diseases. Moreover, modifiable risk factors that link the two diseases may be identified. 11
Prosjekt 166154 Norwegian Epidemiological Osteoporosis Studies. Why does the risk of osteoporotic fractures vary within Norway? Prosjektansvarlig: Institutt for samfunnsmedisinske fag Universitetet i Bergen Prosjektleder: Grethe Seppola Tell Prosjektperiode: 2005 2008 Budsjett: 2,1 mill kr Program/fagkomite: Fagkomiteen for klinisk medisin og folkehelse Norway has the world s highest incidence of osteoporotic fractures. This large public health problem has severe consequences for the individual and for society. Bone mineral density (BMD) is the most widely used measure of bone strength. In spite of large regional differences in fracture risk, few comparative studies have been conducted, and little is known about the causes of these differences. Are they caused by differences in bone strength or tendency for falls? The 4 large epidemiological osteoporosis studies in Norway have established the NOREPOS research collaboration (Tromsø, North-Trøndelag county, Hordaland county and Oslo). BMD has been measured at all study sites, validation and calibration studies have been conducted, and data are now ready for analyses. A substantial amount of work has been laid down in order to make the data from the 4 sites comparable. All NOREPOS studies have applied standardized questionnaires including CONOR (COhort of NORway) questions. NOREPOS data will be used to validate a method for standardizing BMD measurements across sites, investigate differences in BMD and fracture rates between geographic regions, as well as try to explain differences between sites by adjustment for potential confounders. 12
Prosjekt 160372 Primær og sekundær osteoporose (OP) studert ved hjelp av genekspresjonsprofilering i ben Prosjektansvarlig: Institutt for medisinske basalfag Universitetet i Oslo Prosjektleder: Kaare M. Gautvik Prosjektperiode: 2004 2006 Budsjett: 2,3 mill kr Program/fagkomite: Fagkomiteen for molekylær biovitenskap og bioteknologi Prosjektet tar sikte på å kartlegge de molekylære mekanismer som ligger bak utvikling av postmenopausal osteoporose (OP). OP rammer nær halvparten av norske kvinner over 50 år og nær 50 % vil erfare minst en fraktur i løpet av livet. Parathormon (PTH) stimulerer sterkt bennydannelse og arbeidshypotesen er å få en oversikt over alle PTH-regulerte gener i benbiopsier for å isolere den/de med anabol virkning. Dette vil gjøres ved å sammenlikne global genekspresjon i ben hos kontroller og kvinner med OP; gjennom definering av bens fenotype i dyrkede benceller og i pasienter med hyperparathyroidisme før og etter operasjon. Prosjektet vil også vise om det er forskjellige mekanismer som ligger til grunn for ulike typer OP. Kartlegging av de molekylære forandringer som skjer ved osteoporose vil være utgangspunkt for utvikling av nye og bedre behandlingsregimer for OP. Prosjektet søker spesielt etter gener som koder for sekretoriske proteiner som er forskjellig uttrykt hos pasienter med OP og friske og som kan danne grunnlag for nye diagnostiske metoder basert på analyser i serum eller urin. 13
Prosjekt 160369 Anorektisk helsetjeneste: En serie brukerbaserte studier av helsetjeneste karriere og behandlingstilbud til kvinner med alvorlige spiseforstyrrelser. Prosjektansvarlig: Institusjon: Nasjonalt folkehelseinstitutt Prosjektleder: Arne Holte Prosjektperiode: 2004-2007 Budsjett: 1,7 mill kr Program/fagkomite: Program for helsetjenester- og helseøkononomi 2001-2005 Sammendrag: Formålet er å beskrive og forstå kvaliteter i helsetjenesten og helsetjenestetilbud til anorexia nervosa (AN) pasienter slik de erfares fra brukernes side. Følgende tema prioriteres: helsetjenesteatferd og brukerkarriere, møtet med helsetjenestene, behandling ved Modum Bad, diagnostisering av AN, virksomme faktorer i behandling, Bakgrunn: Omfattende forundersøkelse (Espeset & Nordbø, 2002), litteratur, klinisk og forskningserfaring. Design: Triangulert empirisk fenomenologisk, deskriptivt og kvalitativt undersøkelsesopplegg med innslag av Grounded Theory. Informanter: Kvinner i alder 18-35 år behandlet for langt kommet AN i ulike ledd av norsk helsetjeneste. Datainnsamling: Utføres med "opplevelsesintervjuet", et halvåpent informantsentrert strategisk intervjuformat. Dataanalyse: Ordrett transkriberte lydopptak utgjør data. Empirisk fenomenologisk tekstanalyse med innslag av Grounded Theory utføres elektronisk med QSR -N*Vivo. Gjennom åpen, aksial og selektiv koding utvikles fenomenologiske beskrivelser og modeller som fortløpende tilpasses og prøves mot data og deretter kontrolleres opp mot brukere/eksperter. Verifisering: Avansen selvkorrigerende intervjuteknikk, spesialtrenere intervjuere, skrevne utskriftsregler, fortløpende kryss-sjekking av utskrifter mot lydbåndopptak, stikkprøvekoding med to rater, triangulering i flere utvalg, fortløpende overvåking av forskningsprosessen av styrings/ressursgruppe. Etisk vurdering: Helsinkideklarasjonen følges. Prosjektet søkes tilrådet av REK. Vitenskapelig betydning: Statlig høyprioritet område. Brukerbasene erfaringsmodeller som grunnlag for å bygge ut behandling for Europas tredje mest dødelige sykdom for unge kvinner. 14
Prosjekt 160739 Enogent cushing syndrom og steroid indusert osteoporose: Studier på molekylært grunnlag for patofysiologiske forandringer i benmetabolismen Prosjektansvarlig: Klinisk medisin, Inst.gruppe for RH/DNR Universitetet i Oslo Prosjektleder: Jens Bollerslev Prosjektperiode: 2004 Budsjett: kr 735 000 Program/fagkomite: Fagkomiteen for klinisk medisin og folkehelse I Norge finner en den høyeste insidensen av osteoporose og lårhalsbrudd i verden. Den tredje vanligste formen for osteoporose, etter postmenopausal og senil osteoporose, er glukokortikoidindusert osteoporose (GIO). For folkehelsen er osteoporose et alvorlig helseproblem som gir økt sykelighet og mortalitet, og lårhalsbrudd koster det norske samfunn 1.4 milliarder kroner/år. For den enkelte pasient medfører osteoporose økt risiko for benbrudd og nedsatt livskvalitet pga. sterke smerter og komplikasjoner fra brudd. Nyere forskning tyder på at nedsatt benformasjon pga. nedsatt osteoblastogenese kombinert med en økning av apoptose av modne osteoblaster og osteocytter er av sentral betydning for de patofysiologiske forandringene ved GIO. Prosjektgruppen har, i internasjonal sammenheng, samlet et stort materiale (blodprøver, PBMC, benbiopsier, benmineralmålinger) av pasienter med endogent Cushing syndrom. Denne pasientgruppen egner seg meget godt som modell for GIO, og kjennestegnes med kronisk overproduksjon av cortisol. Denne pasientgruppen er "ren" og har ingen annen kjent underliggende sykdom som gir benpatologi. Resultater tyder på en interessant kopling mellom benmetabolismen og immunapparatet, i form av økte serum nivåer av interleukinene IL-8 og IL-18, og disse resultatene har vekket internasjonal oppmerksomhet. Prosjektgruppen ønsker nå å utvide dette studiet og undersøke global genekspresjonen i benbiopsier til denne pasientgruppen i større detalj. 15