Suchergebnisse

Data Availability: Data in this study is third party data, that originates from the Norwegian Mother Child cohort (MoBa). Data is regulated by the MoBa Scientific Management Group. All MoBa used for research is subject to legal restricting which prohibits the authors from making minimal data set publicly available. Data requests that meet the guidelines described in the link below, can be addressed to the MoBa Scientific Management Group. For further information about data access please contact; datatilgang@fhi.no, or Professor Per Magnus mail address: per.magnus@fhi.no. See specific guidelines for research with MoBa data; https://www.fhi.no/globalassets/dokumenterfiler/retningslinjer-moba-eng.pdf. ; Background Dietary habits are linked to high maternal glucose levels, associated with preterm delivery. The aim of this study was to examine the associations between meal frequency and glycemic properties of maternal diet in relation to preterm delivery. Methods This prospective cohort study included 66,000 women from the Norwegian Mother and Child Cohort Study (MoBa). Meal frequency and food intake data were obtained from a validated food frequency questionnaire during mid-pregnancy. Principal component factor analysis was used with a data-driven approach, and three meal frequency patterns were identified: "snack meal", "main meal", and "evening meal". Pattern scores were ranked in quartiles. Glycemic index and glycemic load were estimated from table values. Intakes of carbohydrates, added sugar, and fiber were reported in grams per day and divided into quartiles. Gestational age was obtained from the Medical Birth Registry of Norway. Preterm delivery was defined as birth at <37 gestational weeks. A Cox regression model was used to assess associations with preterm delivery. Results After adjustments, the "main meal" pattern was associated with a reduced risk of preterm delivery, with hazard ratios (HRs) of 0.89 (95% confidence interval (CI): 0.80, 0.98) and 0.90 (95% CI: 0.81, 0.99) for the third and fourth quartiles, respectively, and p for trend of 0.028. This was mainly attributed to the group of women with BMI ≥25 kg/m2, with HRs of 0.87 (95% CI: 0.79, 0.96) and 0.89 (95% CI: 0.80, 0.98) for the third and fourth quartiles, respectively, and p for trend of 0.010. There was no association between glycemic index, glycemic load, carbohydrates, added sugar, fiber, or the remaining meal frequency patterns and preterm delivery. Conclusion Regular consumption of main meals (breakfast, lunch, dinner) was associated with a lower risk of preterm delivery. Diet should be further studied as potential contributing factors for preterm delivery. ; This work was supported by Freemanson's Directorate Board for Children, ES236011, MD Linda Englund Ögge; Adlerbertska Foundation, MD Linda Englund Ögge; the Norwegian Research Council, FUGE 183220/S10, MD Linda Englund Ögge; Norwegian Research Council, FRIMEDKLI-05 ES236011, MD Linda Englund Ögge; Jane and Dan Olsson Foundation, MD Linda Englund Ögge; Swedish Medical Society, SLS 2008-21198, MD Linda Englund Ögge; Swedish government grants to researchers in public health service, ALFGBG-2863, MD Linda Englund Ögge; Swedish government grants to researchers in public health service, ALFGBG-11522, MD Linda Englund Ögge; the Norwegian Ministry of Health and the Ministry of Education and Research, N01-ES-75558; NIH/NINDS, UO1 NS 047537-01; NIH/NINDS, UO1 NS 047537-06A1; Norwegian Research Council/FUGE, 151918/S10. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. ; Peer Reviewed

Publisher's version (útgefin grein) ; Objective:Theobjectiveofthisstudywastounderstandtheeffectofacetylsalicylicacid(aspirin)onresistancearteriesfrommesenteryanduterus.Duringpregnancy,the uterine vasculature undergoes consistent growth to provide sufficient uteroplacental blood flow, a process whose failure is associated with pregnancy compli-cations characterized by high uterine vascular resistance.Methods:Uterine arcuate (UA) and mesenteric arteries (MA; diameter10−7M. Further, uterine vasodilation was significantly reduced when the endothelium wasremoved (p < 0.001), and by inhibitors of nitric oxide synthase (p < 0.001), cyclooxygenase synthase (p < 0.05), cyclic nucleotides cGMP/cAMP and BKchannels.Conclusion:This is the first study to show a direct vasodilatory effect of aspirin on rat uterine artery that is mediated by a combination of cellular – primarilyendothelial - mechanisms. Our results in UA suggest that the use of aspirin may be effective in enhancing uteroplacental blood flow,while its vasodilation effect onMA may lower peripheral resistance. ; This study was supported by grants from the European Union 7th Framework Programme – FP7-HEALTH-2013-INNOVATION-2 (ASPRE Project # 601852), Hananja ehf, and by the Icelandic Research Fund. ; Peer Reviewed

Publisher's version (útgefin grein) ; Purpose: To describe recent international trends in antiepileptic drug (AED) use during pregnancy and individual patterns of use including discontinuation and switching. Methods: We studied pregnancies from 2006 to 2016 within linked population-based registers for births and dispensed prescription drugs from Denmark, Finland, Iceland, Norway, Sweden, and New South Wales, Australia and claims data for public and private insurance enrollees in the United States. We examined the prevalence of AED use: the proportion of pregnancies with ≥1 prescription filled from 3 months before pregnancy until birth, and individual patterns of use by trimester. Results: Prevalence of AED use in almost five million pregnancies was 15.3 per 1000 (n = 75 249) and varied from 6.4 in Sweden to 34.5 per 1000 in the publicly-insured US population. AED use increased in all countries in 2006-2012 ranging from an increase of 22% in Australia to 104% in Sweden, and continued to rise or stabilized in the countries in which more recent data were available. Lamotrigine, clonazepam, and valproate were the most commonly used AEDs in the Nordic countries, United States, and Australia, respectively. Among AED users, 31% only filled a prescription in the 3 months before pregnancy. Most filled a prescription in the first trimester (59%) but few filled prescriptions in every trimester (22%). Conclusions: Use of AEDs in pregnancy rose from 2006 to 2016. Trends and patterns of use of valproate and lamotrigine reflected the safety data available during this period. Many women discontinued AEDs during pregnancy while some switched to another AED. ; This study was funded by NordForsk as part of the Nordic Pregnancy Drug Safety Studies (NorPreSS) (Project No: 83539) and the Research Council of Norway as part of the International Pregnancy Drug Safety Studies (InPreSS) (Project No: 273366). Linkage of Danish data was supported by the Danish Council for Independent Research (Project No: DFF‐6110‐00019) and Karen Elise Jensens Fond (2016), and grant NNF18OC0052029 from Novo Nordisk Fonden (Li). Linkage of the Australian data was supported by an Australian National Health and Medical Research Council Project grant (No. 1028543). We thank Anders Engeland (Norwegian Institute of Public Health, University of Bergen, Norway), Anna Heino (National Institute for Health and Welfare, Finland), Mette Nørgaard (Aarhus University, Denmark), Pär Karlsson (Karolinska Institutet, Sweden), Jennifer Yland (Harvard T.H. Chan School of Public Health, USA), Gregory Brill and Helen Mogun (Brigham and Women's Hospital & Harvard Medical School, USA) for providing assistance with analyses. The authors would like to thank the NSW Ministry of Health, the Australian Government Department of Health and Ageing and the Department of Human Services for providing data. The authors also thank the Centre for Health Record Linkage (CHeReL) and the Australian Institute for Health and Welfare for conducting the linkage of records. ; Peer Reviewed

Publisher's version (útgefin grein) ; Background Mothers' smoking during pregnancy increases asthma risk in their offspring. There is some evidence that grandmothers' smoking may have a similar effect, and biological plausibility that fathers' smoking during adolescence may influence offspring's health through transmittable epigenetic changes in sperm precursor cells. We evaluated the three-generation associations of tobacco smoking with asthma. Methods Between 2010 and 2013, at the European Community Respiratory Health Survey III clinical interview, 2233 mothers and 1964 fathers from 26 centres reported whether their offspring (aged ≤51 years) had ever had asthma and whether it had coexisted with nasal allergies or not. Mothers and fathers also provided information on their parents' (grandparents) and their own asthma, education and smoking history. Multilevel mediation models within a multicentre three-generation framework were fitted separately within the maternal (4666 offspring) and paternal (4192 offspring) lines. Results Fathers' smoking before they were 15 [relative risk ratio (RRR) = 1.43, 95% confidence interval (CI): 1.01–2.01] and mothers' smoking during pregnancy (RRR = 1.27, 95% CI: 1.01–1.59) were associated with asthma without nasal allergies in their offspring. Grandmothers' smoking during pregnancy was associated with asthma in their daughters [odds ratio (OR) = 1.55, 95% CI: 1.17–2.06] and with asthma with nasal allergies in their grandchildren within the maternal line (RRR = 1.25, 95% CI: 1.02–1.55). Conclusions Fathers' smoking during early adolescence and grandmothers' and mothers' smoking during pregnancy may independently increase asthma risk in offspring. Thus, risk factors for asthma should be sought in both parents and before conception. ; The present analyses are part of the Ageing Lungs in European Cohorts (ALEC) Study [www.alecstudy.org], which has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No. 633212. The coordination of the European Community Respiratory Health Survey (ECRHS) was supported by the European Commission (phases 1 and 2) and the Medical Research Council (phase 3). Local funding agencies for the ECRHS are reported in the Supplementary Appendix, available as Supplementary data at IJE online. Conflict of interest: J.W.H. reports grants from the European Union's Horizon 2020 programme (633212), the Medical Research Council UK (MC_PC_15078) and the National Institutes of Health USA (R01 AI091905, R01 AI121226) during the conduct of the study. R.J. reports grants from the Estonian Research Council (personal grant No. 562) during the conduct of the study, grants/grants pending from the Estonian Research Council (personal research grant No. 562), personal fees for consulting and lecturing from GlaxoSmithKline, Boehringer and Novartis and travel/accommodation/meeting expenses paid by GlaxoSmithKline and Boehringer, outside the submitted work. C.R. reports personal fees for consulting and lecturing from ALK, Astra Zeneca, GSK, Boheringer and Novartis, outside the submitted work. A.G.C. reports grants from Chiesi Farmaceutici and GlaxoSmithKline Italy, during the conduct of the study. P.D. reports personal fees for consulting and lecturing from ALK and Stallergenes Greer and personal fees for consulting from Circassia, Chiesi Farmaceutici, ThermofisherScientific and Menarini, outside the submitted work. D.J. reports grants from the Medical Research Council and the European Union's Horizon 2020 programme, during the conduct of the study. All other authors declare no competing interests. ; Peer Reviewed

Inngangur: Þegar kona verður þunguð, eiga sér stað miklar breytingar á æðakerfi hennar, til að mæta aukinni blóðþörf til fylgju og fósturs og tryggja eðlilegan vöxt fóstursins. Til að þetta sé hægt, þarf stækkun á æðum sem flytja blóð til fóstursins að eiga sér stað. Ef þessar breytingar á æðakerfi ná ekki að myndast, getur það leitt til ýmissa meðgöngutengdra sjúkdóma, eins og meðgöngueitrun. Tíðni meðgöngueitrunar er um 2-5% þungana í Evrópu og lýsir sér sem nýtilkominn háþrýstingur og því fylgir mælanlegt prótein í þvagi. Fylgjuprótein 13 (PP13, placental protein 13) er prótein sem er eingöngu seytt af fylgju og mælist í blóði mæðra frá fimmtu viku meðgöngu. Konur sem eru í áhættuhópi reynast vera með mun lægra magn af PP13 í sermi, en konur með heilbrigða meðgöngu. Því hefur verið lagt til að próteinið megi nýtast til greiningar á konum sem eru líklegri að þróa með sér meðgöngueitrun. Markmið: 1) Að skoða skammtíma- og langtímaáhrif proteins á æðakerfið í kringum legið (Grein III). 2) Að skilgreina verkunarmáta próteinsins á einangraðar legæðar úr rottum (Grein I). 3) Að meta áhrif próteinsins á æðakerfið í kringum legið og fósturvöxt í rottum. 4) Að meta lyfjahvörf próteinsins í kanínum (Grein II). Aðferðir og niðurstöður: Osmótískar dælur voru ígræddar í óþungaðar rottur sem losuðu um 10 µl/klst og tæmdu sig á sjö dögum. Sum dýranna (n=11) voru aflifuð eftir sjö daga meðferð til að meta skammtímaáhrifin, en önnur (n=16) voru aflifuð eftir 13 daga til að meta langtímaáhrif próteinsins á æðakerfið. Þvermál slag- og bláæða úr legi voru borin saman á milli hópa. Marktækur munur sást á öllum æðum í bæði langtíma- og skammtímahópnum. Til að skilgreina verkunarhátt fylgjupróteins 13, voru legslagæðar einangraðar og settar í sérhæfðan æðamæli (e. arteriograph). Próteinið reyndist hafa æðavíkkandi áhrif (38-50%) sem hægt var að hemja með því að hinda aðgengi nituroxíðs og arakídónsýru. Áhrifin hurfu ef æðaþelið var fjarlægt. EC50 mældist undir 1pM. Áhrif próteinsins í þunguðum rottum með ígræddar osmótískar dælur sem fengu nituroxíðhindra í drykkjarvatni leiddi í ljós marktækt minni unga samanborið við viðmiðunarhópinn. Þessi áhrif snertu einnig meginlegslagæð (MUA) og legbláæðar (RUV). Lyfjahvörf fylgjupróteins 13, sem fóru fram í kanínum, voru skoðuð með því að gefa þrjá mismunandi styrki af próteininu (5 ng/mL, 10 ng/mL og 50 ng/mL) í æð (I.V.), og síðan einn styrkur (50 ng/mL) var gefinn undir húð (S.C.). Blóðþéttni var mæld með ELISA prófi og lyfjahvarfafræðileg heðgun próteinsins reiknuð út, sem fylgdi svokölluðu tveggja-hólfa kerfi. Helmingunartíminn var marktækt hærri hjá S.C. hópnum (p<0.01), en það kom í ljós að bæði dreifirúmmál og flatarmálið undir ferlinum (AUC) reyndust vera skammtaháð milli I.V. hópanna. Ályktanir: Niðurstöðurnar sýndu að fylgjuprótein 13 hefur veruleg æðavíkkandi áhrif, sem jafnframt hefur jákvæð áhrif á vöxt fylgju og fósturs. Þetta prótein gæti verið lykilþáttur í undirbúningi æðakerfisins fyrir aukið blóðflæði síðar á meðgöngunni. Lyfjahvarfafræðilegar athuganir sýna að magn próteinsins sem er losað úr fylgju gæti verið mun hærri en áður var talið. Frekari rannsókna er þörf til að fá dýpri innsýn í áhrif þessa próteins á æðakerfi manna. Niðurstöður okkar er mikil hvatning fyrir áframhaldandi rannsóknum til að meta fylgjuprótein 13 sem mögulegan lyfjasprota til að fyrirbyggja meðgöngueitrun og aðra meðgöngutenda sjúkdóma sem tengjast ófullnægjandi blóðflæði til legs og fylgju. ; Background: During pregnancy extensive hemodynamic changes are required for optimal fetal growth and utero-placental circulation adaptation to increased blood volume. If those changes are altered or fail to occur they may lead to pathological pregnancies and preeclampsia. Preeclampsia is an obstetrical syndrome associated with high blood pressure and altered organ function that affects 2-5% of pregnant women. Placental protein 13 (PP13) is secreted solely by placenta and has been proposed as a potential biomarker whilst its serum levels in early pregnancy in women at risk are much lower than those in healthy pregnancies. Aims: First, to study the long and short term effects (Paper III), and evaluate overall effect of PP13 exposure on uterine vasculature, and the fetal outcome in rats. Second aim is to define the mechanism of action in isolated rat arteries in vitro (Paper I). The final aim is to evaluate the pharmacokinetic profile of PP13 in rabbits (Paper II). Methods and Main Results: Slow-release osmotic pums loaded with protein or saline were implanted in periscapular region in non-pregnt rats, releasing its content for seven days. Some animals (n=11) were sacrified after seven days with the pump (short-term), and some animals (n=16) were sacrified after thirteen days (long-term). The diameter of arteries and veins were compared between groups, resulting in significant vascular expansion of all vessels in rPP13 group both in short and long-term. Histidine tagged PP13 variant (his-PP13), caused significant vessel expansion in radial arteries, and only in short-term. Study conducted in pregnant rats, by inserting the osmotic pump at the time of placentation, in which some rats were treated with L-NAME via drinking water in order to inhibit the main vasodilation pathway (eNOS). The results showed that rPP13 treated animals had heavier pups and bigger placentas, in comparison to the control. All L-NAME treated groups resulted in significantly smaller pups and placentas in comparison to the control. Main uterine artery (MUA) and radial uterine veins (RUV) expansion in L-NAME treated animals were significatntly lower compared to the control. To study the mechanism of action uterine vessels were isolated and cannulated in arteriograph maintained at constant pressure of 50 mmHg. Vessels were then preconstricted and exposed to increasing concentrations of rPP13 (10-13 to 10-8 M). rPP13 elicited 38-50% arterial vasodilation mediated via endothelial signaling pathways of nitric oxide and arachidonic acid, with half maximal response (EC50) of approx. 1pM. In order to establish pharmacokinetic profile of PP13, three different concentrations of the protein (5 ng/mL, 10 ng/mL and 50 ng/mL) were administrated intravenously (I.V.) and one concentration (50 ng/mL) was administrated subcutaneously (S.C.) in New Zealand White rabbits. The serum levels of the protein were determined by enzyme-linked immunosorbent assay (ELISA). The pharmacokinetic profile is described as two-compartment model. The elimination half-life was found to be different between the groups (p<0.01), and volume of distribution and area under the curve were found to be dose dependent. Conclusion: The results indicate that PP13 is a potent vasodilator, has a positive effect on fetal growth and may be a key factor in preconditioning the uterine vasculature in order to accommodate the blood flow increase during pregnancy. In addition pharmacokinetic studies indicate that the concentration of total PP13 released into maternal circulation may be much higher than previously estimated. Further studies are required in order to get an insight into the effect on human vasculature, however, these results encourage evaluation of PP13 as a potential therapeutic agent for obstetric syndromes characterized by insufficient uteroplacental blood flow. ; The project was funded by: Icelandic Centre for Research (RANNIS), European Union (FP7) through the ASPRE project (601852) and Hananja ehf.

To access publisher's full text version of this article click on the hyperlink below ; Reduced concentrations of placental protein 13 (PP13) during the first trimester of human pregnancy are associated with elevated risk for the subsequent development of preeclampsia, which is one of the deadliest obstetrical complications of pregnancy. Previous studies by our group have shown that PP13 lowers blood pressure in pregnant rats, increases the size and weight of pups and placentas, and induces vasodilation of resistance arteries through endothelial signaling pathways involving endothelial nitric oxid synthase and prostaglandin. In the present study, the effect of PP13 was investigated in nonpregnant female Sprague Dawley rats (n=27). Osmotic pumps were surgically implanted subcutaneously that released a constant dose of PP13 or saline over 7 days. Most animals were sacrificed 6 days after the end of PP13 release (on day 13), while some were sacrificed immediately at the end of day 7 (the last PP13 release day), to compare the short- and long-term impact of PP13 on vessels' growth and size. The uterine vessels were significantly expanded in the group exposed to recombinant PP13 (rPP13) compared to the control (saline) group. Both veins and arteries were significantly expanded by rPP13 with a more pronounced effect after 13 days compared to the corresponding vessels after 7 days. Furthermore, the long-term effect of treatment by rPP13 was more pronounced in the veins compared to the corresponding arteries. The effect of a PP13 variant with a histidine-tag (His-PP13) remained the same between 7 and 13 days. In conclusion, PP13 might play a key role in the expansive remodeling of the uterine vessels, reflecting what would happen if the rat was pregnant, preparing the uterine vascu-lature for the increase in uteroplacental blood flow, which is necessary for normal pregnancy. We suggest that PP13 could act by NO signaling pathways, a hypothesis that requires future study. ; European Union through ASPRE project Icelandic ...

Publisher Copyright: © 2021 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd. ; Objective: Robson's Ten Group Classification System (TGCS) creates clinically relevant sub-groups for monitoring caesarean birth rates. This study assesses whether this classification can be derived from routine data in Europe and uses it to analyse national caesarean rates. Design: Observational study using routine data. Setting: Twenty-seven EU member states plus Iceland, Norway, Switzerland and the UK. Population: All births at ≥22 weeks of gestational age in 2015. Methods: National statistical offices and medical birth registers derived numbers of caesarean births in TGCS groups. Main outcome measures: Overall caesarean rate, prevalence and caesarean rates in each of the TGCS groups. Results: Of 31 countries, 18 were able to provide data on the TGCS groups, with UK data available only from Northern Ireland. Caesarean birth rates ranged from 16.1 to 56.9%. Countries providing TGCS data had lower caesarean rates than countries without data (25.8% versus 32.9%, P = 0.04). Countries with higher caesarean rates tended to have higher rates in all TGCS groups. Substantial heterogeneity was observed, however, especially for groups 5 (previous caesarean section), 6, 7 (nulliparous/multiparous breech) and 10 (singleton cephalic preterm). The differences in percentages of abnormal lies, group 9, illustrate potential misclassification arising from unstandardised definitions. Conclusions: Although further validation of data quality is needed, using TGCS in Europe provides valuable comparator and baseline data for benchmarking and surveillance. Higher caesarean rates in countries unable to construct the TGCS suggest that effective routine information systems may be an indicator of a country's investment in implementing evidence-based caesarean policies. Tweetable abstract: Many European countries can provide Robson's Ten-Group Classification to improve caesarean rate comparisons. ; Peer reviewed

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. ; The main aim of this study was to assess whether a history of abuse, reported during pregnancy, was associated with an operative delivery. Secondly, we assessed if the association varied according to the type of abuse and if the reported abuse had been experienced as a child or an adult. ; The Bidens study, a cohort study in six European countries (Belgium, Iceland, Denmark, Estonia, Norway, and Sweden) recruited 6724 pregnant women attending routine antenatal care. History of abuse was assessed through questionnaire and linked to obstetric information from hospital records. The main outcome measure was operative delivery as a dichotomous variable, and categorized as an elective caesarean section (CS), or an operative vaginal birth, or an emergency CS. Non-obstetrically indicated were CSs performed on request or for psychological reasons without another medical reason. Binary and multinomial regression analysis were used to assess the associations. ; Among 3308 primiparous women, sexual abuse as an adult (≥ 18 years) increased the risk of an elective CS, Adjusted Odds Ratio 2.12 (1.28-3.49), and the likelihood for a non-obstetrically indicated CS, OR 3.74 (1.24-11.24). Women expressing current suffering from the reported adult sexual abuse had the highest risk for an elective CS, AOR 4.07 (1.46-11.3). Neither physical abuse (in adulthood or childhood <18 years), nor sexual abuse in childhood increased the risk of any operative delivery among primiparous women. Among 3416 multiparous women, neither sexual, nor emotional abuse was significantly associated with any kind of operative delivery, while physical abuse had an increased AOR for emergency CS of 1.51 (1.05-2.19). ; Sexual abuse as an adult increases the risk of an elective CS among women with no prior birth experience, in particular for non-obstetrical reasons. Among multiparous ...