Interpregnancy weight change and recurrence of gestational diabetes mellitus: a population-based cohort study

Objective: To estimate recurrence risk of gestational diabetes mellitus (GDM) by interpregnancy weight change. Design: Population-based cohort study. Setting and population: Data from the Swedish (1992–2010) and the Norwegian (2006–2014) Medical Birth Registries on 2763 women with GDM in first pregnancy, registered with their first two singleton births and available information on height and weight. Methods: Interpregnancy weight change (BMI in second pregnancy minus BMI in first pregnancy) was categorised in six groups by BMI units. Relative risks (RRs) of GDM recurrence were obtained by general linear models for the binary family and adjusted for confounders. Analyses were stratified by BMI in first pregnancy (<25 and ≥25 kg/m2). Main outcome measure: GDM in second pregnancy. Results: Among overweight/obese women (BMI ≥25), recurrence risk of GDM decreased in women who reduced their BMI by 1–2 units (relative risk [RR] 0.80, 95% CI 0.65–0.99) and >2 units (RR 0.72, 95% CI 0.59–0.89) and increased if BMI increased by ≥4 units (RR 1.26, 95% CI 1.05–1.51) compared wth women with stable BMI (−1 to 1 units). In normal weight women (BMI <25), risk of GDM recurrence increased if BMI increased by 2–4 units (RR 1.32, 95% CI 1.08–1.60) and ≥4 units (RR 1.61, 95% CI 1.28–2.02) compared with women with stable BMI. Conclusion: Interpregnancy weight loss reduced risk of GDM recurrence in overweight/obese women. Weight gain between pregnancies increased recurrence risk for GDM in both normal and overweight/obese women. Our findings highlight the importance of weight management in the interconception window in women with a history of GDM.publishedVersio

Kunskapsunderlag för ekosystembaserad havsförvaltning i Bottenhavet

Ekosystembaserad havsförvaltning anges som ett viktigt verktyg för att nå Sveriges miljömål. Denna rapport tar ett första steg i riktning mot ett vetenskapligt underlag för att stödja ekosystembaserad havsförvaltning i ett pilotområde i södra Bottenhavet. Ekosystemkomponenter (dvs. arter och livsmiljöer) som är viktiga för modellering av ekosystemet identifieras och deras status samt faktorer som påverkar dem redovisas. Även kunskapsluckor kopplade till påverkansfaktorer diskuteras, samt hur dessa påverkansfaktorer integreras med ekosystemkomponenterna, liksom vilka ekosystemtjänster som ekosystemkomponenterna bidrar till. Många av ekosystemkomponenterna har inte god miljöstatus, särskilt grunda bottnar som har ett högt exploateringstryck. Oroväckande nog saknas det övervakning av både grunda kustnära mjukbottnar och utsjöbankar, fastän dessa områden är av intresse för exploatering samtidigt som de har hög biodiversitet och är kopplade till många ekosystemtjänster. Dock finns det en del data tillgängligt i området som kan användas vid modellering för att ta fram kartor över ekosystemkomponenter och även ekosystemtjänster, som kan vara viktiga underlag för ekosystembaserad förvaltning i södra Bottenhavet. I flera fall är kunskapen om belastningar i södra Bottenhavet och hur de kopplar till statusen av ekosystemkomponenter relativt god, men det saknas information om kumulativa effekter av påverkansfaktorer. Många av de marina arter som finns längst in i Östersjön lever här vid sin nordliga utbredningsgräns, vilket kan innebära att de är extra känsliga för mänskliga belastningar och klimatförändring. Storskaligt fiske efter strömming i utsjön och dess effekter på strömmingsbestånden kan påverka ekosystemets funktion. Strömmingen är talrik och spelar en stor roll i södra Bottenhavets ekosystem. Eftersom strömming vandrar mellan utsjön och kusten kan den koppla samman näringsvävar i kust och utsjö. I Bottenhavets område kan man se tydliga intressekonflikter gällande resursförvaltning. Traditionella lokala näringar baserar sig mycket på fiske av strömming och laxfisk, men vikande fångster av den mer storvuxna strömming som fiskas för humankonsumtion, liksom av laxfisk, skapar problem för det kustnära yrkesfisket. Här finns en uppenbar konkurrenssituation både med det storskaliga pelagiska fisket i utsjön och med naturliga predatorer. Dessa konflikter är svåra att lösa med de förvaltningsmetoder som används idag. Södra Bottenhavets ekosystem skulle sannolikt gynnas av en mer helhetsbaserad förvaltning av fiskbestånden och livsmiljöer, utifrån samtliga faktorer som påverkar dem. I kustområdet gäller detta även, inte minst, de områden där gösens och sikens status är mycket svag, liksom viktiga områden för rekrytering av gädda. En sådan mer helhetsbaserad förvaltning innefattar en samplanering av fiskeregleringar, skyddade områden och åtgärder för att restaurera och skydda diverse livsmiljöer. Förbättring av livsmiljöer för fisk förväntas även gynna andra delar av den biologiska mångfalden och ekosystemtjänster, inklusive olika arters motståndskraft och förmåga att anpassa sig till pågående klimatförändringar

Pathways to child and adolescent psychiatric clinics: a multilevel study of the significance of ethnicity and neighbourhood social characteristics on source of referral

<p>Abstract</p> <p>Background</p> <p>In the Swedish society, as in many other societies, many children and adolescents with mental health problems do not receive the help they need. As the Swedish society becomes increasingly multicultural, and as ethnic and economic residential segregation become more pronounced, this study utilises ethnicity and neighbourhood context to examine referral pathways to child and adolescent psychiatric (CAP) clinics.</p> <p>Methods</p> <p>The analysis examines four different sources of referrals: family referrals, social/legal agency referrals, school referrals and health/mental health referrals. The referrals of 2054 children aged 11-19 from the Stockholm Child-Psychiatric Database were studied using multilevel logistic regression analyses.</p> <p>Results</p> <p>Results indicate that ethnicity played an important role in how children and adolescents were referred to CAP-clinics. Family referrals were more common among children and adolescents with a Swedish background than among those with an immigrant background. Referrals by social/legal agencies were more common among children and adolescents with African and Asian backgrounds. Children with Asian or South American backgrounds were more likely to have been referred by schools or by the health/mental health care sector. A significant neighbourhood effect was found in relation to family referrals. Children and adolescents from neighbourhoods with low levels of socioeconomic deprivation were more likely to be referred to CAP-clinics by their families in comparison to children from other neighbourhoods. Such differences were not found in relation in relation to the other sources of referral.</p> <p>Conclusions</p> <p>This article reports findings that can be an important first step toward increasing knowledge on reasons behind differential referral rates and uptake of psychiatric care in an ethnically diverse Swedish sample. These findings have implications for the design and evaluation of community mental health outreach programs and should be considered when developing measures and strategies intended to reach and help children with mental health problems. This might involve providing information about the availability and accessibility of health care for children and adolescents with mental health problems to families in certain neighbourhoods and with different ethnic backgrounds.</p

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Biochemical and Epidemiological Studies of Early-Onset and Late-Onset Pre-Eclampsia

Biochemical and epidemiological aspects of pre-eclampsia were investigated, with the main focus on possible pathophysiological differences between early-onset and late-onset disease. In pre-eclamptic women poor correlation was found between albumin-creatinine ratio (ACR) in a random urine sample and total amount of albumin in a 24-hour urine collection. (Paper I) In a cohort of women giving birth in Sweden in 1973-82 we estimated the adjusted incidence rate ratio (IRR) for ischaemic heart disease (IHD) during the years 1987–2001. The adjusted IRR for development of IHD was 1.6-2.8 in woman exposed to gestational hypertensive disease during her pregnancy compared with unexposed women. The higher risk represents more severe or recurrent hypertensive disease. (Paper II) Before delivery, in early-onset pre-eclampsia (24-32 weeks) there were pronounced alterations in plasma concentrations of soluble fms-like tyrosine kinase 1 (sFlt1) and placental growth factor (PlGF), and also a higher placental 8-iso-PGF2α concentration and an elevated serum ratio of plasminogen-activator inhibitor (PAI)-1 to PAI-2 compared with early controls. In late-onset pre-eclampsia (35-42 weeks) there were only moderate alterations in sFlt1 and PlGF concentrations, and the placental 8-iso-PGF2α concentration and PAI-1/ PAI-2 ratio were similar to those in late controls. (Papers III, V) There was a rapid postpartum decrease in sFlt1 concentration in all groups. One week postpartum the sFlt1 concentration was persistently higher, however, in women with early-onset pre-eclampsia compared with early controls. (Paper IV) In conclusion: random ACR cannot replace 24-hour urine collections for quantification of albuminuria in pre-eclamptic women; gestational hypertensive disease, especially severe or recurrent, increases the risk for later IHD; early-onset, but not late-onset pre-eclampsia is associated with pronounced alterations of angiogenesis-related markers and only early-onset pre-eclampsia is associated with placental oxidative stress and an increased PAI-1/ PAI-2 ratio, all suggesting a stronger link between early-onset than late-onset pre-eclampsia and a dysfunctional placenta

Biochemical and Epidemiological Studies of Early-Onset and Late-Onset Pre-Eclampsia

Biochemical and epidemiological aspects of pre-eclampsia were investigated, with the main focus on possible pathophysiological differences between early-onset and late-onset disease. In pre-eclamptic women poor correlation was found between albumin-creatinine ratio (ACR) in a random urine sample and total amount of albumin in a 24-hour urine collection. (Paper I) In a cohort of women giving birth in Sweden in 1973-82 we estimated the adjusted incidence rate ratio (IRR) for ischaemic heart disease (IHD) during the years 1987–2001. The adjusted IRR for development of IHD was 1.6-2.8 in woman exposed to gestational hypertensive disease during her pregnancy compared with unexposed women. The higher risk represents more severe or recurrent hypertensive disease. (Paper II) Before delivery, in early-onset pre-eclampsia (24-32 weeks) there were pronounced alterations in plasma concentrations of soluble fms-like tyrosine kinase 1 (sFlt1) and placental growth factor (PlGF), and also a higher placental 8-iso-PGF2α concentration and an elevated serum ratio of plasminogen-activator inhibitor (PAI)-1 to PAI-2 compared with early controls. In late-onset pre-eclampsia (35-42 weeks) there were only moderate alterations in sFlt1 and PlGF concentrations, and the placental 8-iso-PGF2α concentration and PAI-1/ PAI-2 ratio were similar to those in late controls. (Papers III, V) There was a rapid postpartum decrease in sFlt1 concentration in all groups. One week postpartum the sFlt1 concentration was persistently higher, however, in women with early-onset pre-eclampsia compared with early controls. (Paper IV) In conclusion: random ACR cannot replace 24-hour urine collections for quantification of albuminuria in pre-eclamptic women; gestational hypertensive disease, especially severe or recurrent, increases the risk for later IHD; early-onset, but not late-onset pre-eclampsia is associated with pronounced alterations of angiogenesis-related markers and only early-onset pre-eclampsia is associated with placental oxidative stress and an increased PAI-1/ PAI-2 ratio, all suggesting a stronger link between early-onset than late-onset pre-eclampsia and a dysfunctional placenta

Kaliningrad : ett förvandlat Ryssland i ett omdanat Europa

Validerat; 20101217 (root

Clinical Risk Assessment in Early Pregnancy for Preeclampsia in nulliparous Women: A Population Based Cohort Study

Objective To evaluate the capacity of multivariable prediction of preeclampsia during pregnancy, based on detailed routinely collected early pregnancy data in nulliparous women. Design and setting A population-based cohort study of 62 562 pregnancies of nulliparous women with deliveries 2008–13 in the Stockholm-Gotland Counties in Sweden. Methods Maternal social, reproductive and medical history and medical examinations (including mean arterial pressure, proteinuria, hemoglobin and capillary glucose levels) routinely collected at the first visit in antenatal care, constitute the predictive variables. Predictive models for preeclampsia were created by three methods; logistic regression models using 1) pre-specified variables (similar to the Fetal Medicine Foundation model including maternal factors and mean arterial pressure), 2) backward selection starting from the full suite of variables, and 3) a Random forest model using the same candidate variables. The performance of the British National Institute for Health and Care Excellence (NICE) binary risk classification guidelines for preeclampsia was also evaluated. The outcome measures were diagnosis of preeclampsia with delivery Results A total of 2 773 (4.4%) nulliparous women subsequently developed preeclampsia. The pre-specified variables model was superior the other two models, regarding prediction of preeclampsia with deliveryweeks, both with areas under the curve of 0.68, and sensitivity of 30.6% (95% CI 24.5–37.2) and 29.2% (95% CI 25.2–33.4) at a 10% false positive rate, respectively. The performance of these customizable multivariable models at the chosen false positive rate, was significantly better than the binary NICE-guidelines for preeclampsia with delivery≥37 weeks’ gestation. Conclusion Multivariable models in early pregnancy had a modest performance, although providing advantages over the NICE-guidelines, in predicting preeclampsia in nulliparous women. Use of a machine learning algorithm (Random forest) did not result in superior prediction

Multi-Fetal Pregnancy, Preeclampsia, and Long-Term Cardiovascular Disease

This Swedish register-based cohort study determined the separate and joint contribution of preeclampsia and multi-fetal pregnancy on a woman’s risk of cardiovascular disease (CVD) later in life. The study included 892 425 first deliveries between 1973 and 2010 of women born 1950 until 1971, identified in the Swedish Medical Birth Register. A composite outcome of CVD was retrieved through linkage with the National Patient and Cause of Death Registers. Cox proportional hazard regression was used to assess the risk of CVD in women who had preeclampsia in a singleton or multi-fetal pregnancy, adjusting for potential confounders, and presented as adjusted hazard ratios. Compared with women who had a singleton pregnancy without preeclampsia (the referent group), women with preeclampsia in a singleton pregnancy had an increased risk of CVD (adjusted hazard ratio 1.75 [95% CI, 1.64–1.86]). Women who had a multi-fetal pregnancy without or with preeclampsia did not have an increased risk of future CVD (adjusted hazard ratios 0.94 [95% CI, 0.79–1.10] and 1.25 [95% CI, 0.83–1.86], respectively). As opposed to preeclampsia in a first singleton pregnancy, preeclampsia in a first multi-fetal pregnancy was not associated with increased risk of future CVD. This may support the theory that preeclampsia in multi-fetal pregnancies more often occurs as a result of the larger pregnancy-related burden on the maternal cardiovascular system and excessive placenta-shed inflammatory factors, rather than the woman’s underlying cardiovascular phenotype