Browsing by Subject "Preeclampsia"

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  • Jääskeläinen, Tiina; Kärkkäinen, Olli; Jokkala, Jenna; Klåvus, Anton; Heinonen, Seppo; Auriola, Seppo; Lehtonen, Marko; FINNPEC Core Invest Grp; Hanhineva, Kati; Laivuori, Hannele (2021)
    IntroductionMaternal metabolism changes substantially during pregnancy. However, few studies have used metabolomics technologies to characterize changes across gestation.Objectives and methodsWe applied liquid chromatography-mass spectrometry (LC-MS) based non-targeted metabolomics to determine whether the metabolic profile of serum differs throughout the pregnancy between pre-eclamptic and healthy women in the FINNPEC (Finnish Genetics of Preeclampsia Consortium) Study. Serum samples were available from early and late pregnancy.ResultsProgression of pregnancy had large-scale effects to the serum metabolite profile. Altogether 50 identified metabolites increased and 49 metabolites decreased when samples of early pregnancy were compared to samples of late pregnancy. The metabolic signatures of pregnancy were largely shared in pre-eclamptic and healthy women, only urea, monoacylglyceride 18:1 and glycerophosphocholine were identified to be increased in the pre-eclamptic women when compared to healthy controls.ConclusionsOur study highlights the need of large-scale longitudinal metabolomic studies in non-complicated pregnancies before more detailed understanding of metabolism in adverse outcomes could be provided. Our findings are one of the first steps for a broader metabolic understanding of the physiological changes caused by pregnancy per se.
  • Karppanen, Tiina; Kaartokallio, Tea; Klemetti, Miira M.; Heinonen, Seppo; Kajantie, Eero; Kere, Juha; Kivinen, Katja; Pouta, Anneli; Staff, Anne Cathrine; Laivuori, Hannele (2016)
    Background: Preeclampsia is a common and heterogeneous vascular syndrome of pregnancy. Its genetic risk profile is yet unknown and may vary between individuals and populations. The rs4606 3'UTR polymorphism of the Regulator of G-protein signaling 2 gene (RGS2) in the mother has been implicated in preeclampsia as well as in the development of chronic hypertension after preeclampsia. The RGS2 protein acts as an inhibitor of physiological vasoconstrictive pathways, and a low RGS2 level is associated with hypertension and obesity, two conditions that predispose to preeclampsia. We genotyped the rs4606 polymorphism in 1339 preeclamptic patients and in 697 controls from the Finnish Genetics of Preeclampsia Consortium (FINNPEC) cohort to study the association of the variant with preeclampsia. Results: No association between rs4606 and preeclampsia was detected in the analysis including all women. However, the polymorphism was associated with preeclampsia in a subgroup of overweight women (body mass index >= 25 kg/m(2), and <30 kg/m(2)) (dominant model; odds ratio, 1.64; 95 % confidence interval, 1.10-2.42). Conclusions: Our results suggest that RGS2 might be involved in the pathogenesis of preeclampsia particularly in overweight women and contribute to their increased risk for hypertension and other types of cardiovascular disease later in life.
  • Ervaala, Attina (Helsingin yliopisto, 2021)
    Pre-eklampsia on globaali ongelma, mikä komplisoi 2–8 % raskauksista. Pre-eklampsiassa normaalisti sikiötä äidin immuunipuolustukselta suojaavien tekijöiden säätely on häiriintynyt. Tutkimuksen tarkoituksena oli selvittää pre-eklampsian riskiä ja luonnetta luovutetuilla sukusoluilla saavutetuissa raskauksissa. Koska luovutetut sukusolut eroavat immunologisesti normaalia enemmän kantajastaan, hypoteesiksi asetettiin, että näissä raskauksissa pre-eklampsiaa esiintyy enemmän. Myös kirjallisuuden mukaan näissä raskauksissa vaikuttaisi olevan pre-eklampsiaa enemmän (38–20 %). Aineistona oli Finnish Genetics of Preeclampsia Consortium (FINNPEC) kohortti (n=2778). Tässä pre-eklampsia määriteltiin seuraavasti: 1. yli 140 mmHg:n systolinen verenpaine sekä 2. proteinuria (virtsan proteiini ≥0·3 g/24 h tai 0·3 g/L tai kaksi ≥1+ tulosta liuskatestissä) ja 3. näiden ilmeneminen H20 jälkeen. Näillä kriteereillä verrattiin luovutetuilla sukusoluilla saavutettuja raskauksia (n=21) muihin raskauksiin (n=2757). Väestötason esiintyvyys pre-eklampsian suhteen saatiin terveyden ja hyvinvoinnin laitoksen syntyneiden lasten rekisteristä. Tutkimuksen tuloksena todettiin pre-eklampsiaa esiintyvän enemmän luovutetuilla sukusoluilla saavutetuissa raskauksissa. Muita riskitekijöitä olivat muun muassa äidin korkeampi ikä ja sikiön miessukupuoli. Pre-eklampsiaraskauksia vertailtaessa luovutetuilla sukusoluilla saavutetuissa raskauksissa esiintyi enemmän ennenaikaisia synnytyksiä, ja pre-eklampsia diagnosoitiin aiemmin kuin muissa raskauksissa. Luovutettujen sukusolujen raskauksista ei löydetty tilastollisesti merkittäviä eroja raskauksien luonteissa luovutettujen siittiöiden ja munasolujen välillä, mutta näyttäisi siltä, että riskit ovat isommat luovutetuilla munasoluilla alkaneissa raskauksissa. Tulokset tukevat aikaisempia tutkimustuloksia, vaikka otanta olikin pieni. Tilastollisten merkitsevien erojen puuttumisesta huolimatta tutkimus mahdollisti lisätiedon saamisen sikiön sukupuolen ja vieraiden antigeenien merkityksestä.
  • Wedenoja, Satu; Yoshihara, Masahito; Teder, Hindrek; Sariola, Hannu; Gissler, Mika; Katayama, Shintaro; Wedenoja, Juho; Häkkinen, Inka M. K.; Ezer, Sini; Linder, Nina; Lundin, Johan; Skoog, Tiina; Sahlin, Ellika; Iwarsson, Erik; Pettersson, Karin; Kajantie, Eero; Mokkonen, Mikael; Heinonen, Seppo; Laivuori, Hannele; Krjutskov, Kaarel; Kere, Juha (2020)
    Background: Fetal immune tolerance is crucial for pregnancy success. We studied the link between preeclampsia, a severe pregnancy disorder with uncertain pathogenesis, and fetal human leukocyte antigen G (HLA-G) and other genes regulating maternal immune responses. Methods: We assessed sex ratios and regulatory HLA-G haplotypes in population cohorts and series of preeclampsia and stillbirth. We studied placental mRNA expression of 136 genes by sequencing and HLA-G and interferon alpha (IFN alpha) protein expression by immunohistochemistry. Findings: We found underrepresentation of males in preeclamptic births, especially those delivered preterm or small for gestational age. Balancing selection at HLA-G associated with the sex ratio, stillbirth, and preeclampsia. We observed downregulation of HLA-G, its receptors, and many other tolerogenic genes, and marked upregulation of IFNA1 in preeclamptic placentas. Interpretation: These findings indicate that an evolutionary trade-off between immune tolerance and protection against infections at the maternal-fetal interface promotes genetic diversity in fetal HLA-G, thereby affecting survival, preeclampsia, and sex ratio. We highlight IFNA1 as a potential mediator of preeclampsia and a target for therapeutic trials. (C) 2020 The Authors. Published by Elsevier B.V.
  • Kvehaugen, Anne Stine; Melien, Oyvind; Holmen, Oddgeir L.; Laivuori, Hannele; Dechend, Ralf; Staff, Anne Cathrine (2014)
  • Lokki, A. Inkeri; Heikkinen-Eloranta, Jenni (2021)
    Preeclampsia is a multifactorial vascular disease unique to human pregnancy. While genetic and antiangiogenic factors are important contributors to preeclampsia susceptibility, recent studies have shown that dysregulation and/or over-activation of the complement system has an integral role in dis-ease etiology. Furthermore, the role of the coagulation cascade may be underappreciated in the develop-ment of the disease. Traditionally, for research purposes, the pool of preeclampsia cases has been divided into non-severe and severe disease depending on the onset and severity of the symptoms. However, of particular interest are a small but important minority of cases that present with symptoms likening to those of hemolysis, elevated liver enzymes and low platelets syndrome, atypical hemolytic uremic syn-drome, or thrombotic thrombocytopenic purpura, all thrombotic microangiopathy (TMA) diseases, with the hallmark mechanisms of endothelial dysfunction and aberrant activation of complement and coagu-lation cascades. We therefore propose a third class, severe TMA-like preeclampsia to be included in the categorization of preeclampsia patients. Identifying these patients would target research, diagnostic dif-ferentiation, and novel treatment options to the subclass of patients with life-threatening disease that are most likely to benefit from next-generation drug development. (c) 2021 The Authors. Published by Elsevier Inc. on behalf of American Society for Histocompatibility and Immunogenetics. This is an open access article under the CC BY-NC-ND license (http://creativecommons. org/licenses/by-nc-nd/4.0/).
  • Suuronen, Sonja; Jääskeläinen, Tiina; Kortelainen, Eija; Kaartokallio, Tea; Pulkki, Kari; Romppanen, Jarkko; Heinonen, Seppo; Laivuori, Hannele (Helsingin yliopisto, 2021)
    Introduktion: Preeklampsi är ett syndrom med en mångsidig fenotyp. Vi forskade om kliniska egenskaper av prematura och fullgångna graviditeter i FINNPEC (Finnish Genetics of Pre-eclampsia Consortium) -kohorten Material och metoder: Vi undersökte kliniska fenotyper hos 2541 kvinnor i FINNPEC. Angiogena markörer var tillgängliga i en delkohort. Jämförelser utfördes mellan fyra grupper: prematur preeklampsi, fullgången preeklampsi, prematur kontroll och fullgången kontroll. Resultat: Av 1460 kvinnor med preeklampsi födde 37,9 % prematurt och i kontrollgruppen bestående av 1081 kvinnor födde 6,8 % prematurt. Kroppsmasseindexet (BMI) före graviditeten var högre i prematur preeklampsi jämfört med prematurkontrollen och i fullgången preeklampsi jämfört med fullgångna kontrollen. Prevalensen av kronisk hypertoni ökade både i prematur preeklampsi- och kontrollgrupper jämfört med deras respektive fullgångna grupper. Mellan de fullgångna grupperna, drabbades kvinnor med preeklampsi oftare av kronisk hypertoni. Kvinnor i de prematura grupperna födde oftare barn med låg födelsevikt för åldern (SGA) och barnen hade lägre relativt födelsevikt än i de respektive fullgångna grupperna. Prematura kontroller födde oftare barn med låg födelsevikt för åldern jämfört med prematur preeklampsigruppen och samma gällde kvinnor i de fullgångna grupperna. Markörprofilen under graviditeten var mera antiangiogen i preeklampsigrupperna. Slutsatser: Det uppkom signifikanta skillnader i kliniska egenskaper och angiogena markörer mellan de fyra grupperna. Prematur preeklampsi- och kontrollgrupperna var märkbart liknande, vilket återspeglar en möjlig fenotypisk kontinuitet mellan dessa. (216 ord)
  • Teirilä, Laura; Heikkinen-Eloranta, Jenni; Kotimaa, Juha; Meri, Seppo; Lokki, A. Inkeri (2019)
    Preeclampsia is a serious vascular complication of the human pregnancy, whose etiology is still poorly understood. In preeclampsia, exacerbated apoptosis and fragmentation of the placental tissue occurs due to developmental qualities of the placental trophoblast cells and/or mechanical and oxidative distress to the syncytiotrophoblast, which lines the placental villi. Dysregulation of the complement system is recognized as one of the mechanisms of the disease pathology. Complement has the ability to promote inflammation and facilitate phagocytosis of placenta-derived particles and apoptotic cells by macrophages. In preeclampsia, an overload of placental cell damage or dysregulated complement system may lead to insufficient clearance of apoptotic particles and placenta-derived debris. Excess placental damage may lead to sequestration of microparticles, such as placental vesicles, to capillaries in the glomeruli of the kidney and other vulnerable tissues. This phenomenon could contribute to the manifestations of typical diagnostic symptoms of preeclampsia: proteinuria and new-onset hypertension. In this review we propose that the complement system may serve as a regulator of the complex tolerance and clearance processes that are fundamental in healthy pregnancy. It is therefore recommended that further research be conducted to elucidate the interactions between components of the complement system and immune responses in the context of complicated and healthy pregnancy.
  • Petersen., Sindre H.; Bergh, Christina; Gissler, Mika; Åsvold, Bjørn O.; Romundstad, Liv B.; Tiitinen, Aila; Spangmose, Anne L.; Pinborg, Anja; Wennerholm, Ulla-Britt; Henningsen, Anna-Karina A.; Opdahl, Signe (2020)
    Background The use of assisted reproductive technology (ART) is increasing worldwide and conception after assisted reproduction currently comprises 3-6% of birth cohorts in the Nordic countries. The risk of placenta-mediated pregnancy complications is higher after ART compared to spontaneously conceived pregnancies. Whether the excess risk of placenta-mediated pregnancy complications in pregnancies following assisted reproduction has changed over time, is unknown. Objectives To investigate whether time trends in risk of pregnancy complications (hypertensive disorders in pregnancy, placental abruption and placenta previa) differ for pregnancies after ART compared to spontaneously conceived pregnancies during three decades of assisted reproduction treatment in the Nordic countries. Study Design In a population-based cohort study, with data from national health registries in Denmark (1994-2014), Finland (1990-2014), Norway (1988-2015) and Sweden (1988-2015), we included 6,830,578 pregnancies resulting in delivery. Among these, 146,998 (2.2%) were pregnancies after assisted reproduction (125,708 singleton pregnancies, 20,668 twin pregnancies and 622 of higher order plurality) and 6,683,132 (97.8%) pregnancies were conceived spontaneously (6,595,185 singleton pregnancies, 87,106 twin pregnancies and 1,289 of higher order plurality). We used logistic regression with post-estimation to estimate absolute risks and risk differences for each complication. We repeated analyses for singleton and twin pregnancies, separately. In sub-samples with available information, we also adjusted for maternal body mass index, smoking during pregnancy, previous cesarean section, culture duration and cryopreservation. Results The risk of each placental complication was consistently higher in pregnancies following ART compared to spontaneously conceived pregnancies across the study period, except for hypertensive disorders in twin pregnancies, where risks were similar. Risk of hypertensive disorders increased over time in twin pregnancies for both conception methods, but more strongly for pregnancies following ART (risk difference 1.73 percentage points per 5 years, 95% confidence interval 1.35 to 2.11) than for spontaneously conceived twins (risk difference 0.75 percentage points, 95% confidence interval 0.61 to 0.89). No clear time trends were found for hypertensive disorders in singleton pregnancies. Risk of placental abruption decreased over time in all groups (risk difference -0.16 percentage points, 95% confidence interval -0.19 to -0.12 and -0.06 percentage points, 95% confidence interval -0.06 to -0.05 for pregnancies after assisted reproduction and spontaneously conceived pregnancies, respectively, for singletons and multiple pregnancies combined). Over time, the risk of placenta previa increased in pregnancies after assisted reproduction among both singletons (risk difference 0.21 percentage points, 95% confidence interval 0.14 to 0.27) and twins (risk difference 0.30 percentage points, 95% confidence interval 0.16 to 0.43), but remained stable in spontaneously conceived pregnancies. When adjusting for culture duration, the temporal increase in placenta previa became weaker in all groups of ART pregnancies, whereas adjustment for cryopreservation moderately attenuated trends in ART twin pregnancies. Conclusions The risk of placenta-mediated pregnancy complications following ART remains higher compared to spontaneously conceived pregnancies, despite declining rates of multiple pregnancies. For hypertensive disorders in pregnancy and placental abruption, pregnancies after assisted reproduction follow the same time trends as the background population, whereas for placenta previa, risk has increased over time in pregnancies after ART.
  • Villa, Pia M.; Hämäläinen, Esa; Maki, Annukka; Räikkönen, Katri; Pesonen, Anu-Katriina; Taipale, Pekka; Kajantie, Eero; Laivuori, Hannele (2013)