Browsing by Subject "PREECLAMPSIA"

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  • Yeung, Edwina H.; Guan, Weihua; Zeng, Xuehuo; Salas, Lucas A.; Mumford, Sunni L.; de Prado Bert, Paula; van Meel, Evelien R.; Malmberg, Anni; Sunyer, Jordi; Duijts, Liesbeth; Felix, Janine F.; Czamara, Darina; Hämäläinen, Esa; Binder, Elisabeth B.; Räikkönen, Katri; Lahti, Jari; London, Stephanie J.; Silver, Robert M.; Schisterman, Enrique F. (2020)
    Background Prenatal inflammation has been proposed as an important mediating factor in several adverse pregnancy outcomes. C-reactive protein (CRP) is an inflammatory cytokine easily measured in blood. It has clinical value due to its reliability as a biomarker for systemic inflammation and can indicate cellular injury and disease severity. Elevated levels of CRP in adulthood are associated with alterations in DNA methylation. However, no studies have prospectively investigated the relationship between maternal CRP levels and newborn DNA methylation measured by microarray in cord blood with reasonable epigenome-wide coverage. Importantly, the timing of inflammation exposure during pregnancy may also result in different effects. Thus, our objective was to evaluate this prospective association of CRP levels measured during multiple periods of pregnancy and in cord blood at delivery which was available in one cohort (i.e., Effects of Aspirin in Gestation and Reproduction trial), and also to conduct a meta-analysis with available data at one point in pregnancy from three other cohorts from the Pregnancy And Childhood Epigenetics consortium (PACE). Secondarily, the impact of maternal randomization to low dose aspirin prior to pregnancy on methylation was assessed. Results Maternal CRP levels were not associated with newborn DNA methylation regardless of gestational age of measurement (i.e., CRP at approximately 8, 20, and 36 weeks among 358 newborns in EAGeR). There also was no association in the meta-analyses (all p > 0.5) with a larger sample size (n = 1603) from all participating PACE cohorts with available CRP data from first trimester (<18 weeks gestation). Randomization to aspirin was not associated with DNA methylation. On the other hand, newborn CRP levels were significantly associated with DNA methylation in the EAGeR trial, with 33 CpGs identified (FDR corrected p <0.05) when both CRP and methylation were measured at the same time point in cord blood. The top 7 CpGs most strongly associated with CRP resided in inflammation and vascular-related genes. Conclusions Maternal CRP levels measured during each trimester were not associated with cord blood DNA methylation. Rather, DNA methylation was associated with CRP levels measured in cord blood, particularly in gene regions predominately associated with angiogenic and inflammatory pathways.
  • Lokki, A. Inkeri; Haapio, Mikko; Heikkinen-Eloranta, Jenni (2020)
    Preeclampsia is a pregnancy-specific disorder affecting ca 3% of all pregnant women. Preeclampsia is the source of severe pregnancy complications. Later life consequences for mother and infant include increased risk of cardiovascular disease. Preeclampsia is caused by the dysfunction of the endothelium with subsequent activation of complement and coagulation systems. HELLP syndrome is considered to be an extreme complication of preeclampsia but it can also present independently. Diagnostic symptoms in HELLP syndrome are Hemolysis, Elevated Liver enzymes, and Low Platelets. Similar phenotype is present in thrombotic microangiopathies (TMAs) and HELLP syndrome is considered part of the TMA spectrum. Here, we present a case of severe preeclampsia and HELLP syndrome, which exacerbated rapidly and eventually led to need of intensive care, plasma exchange, and hemodialysis. The patient showed signs of hemolysis, disturbance in the coagulation, and organ damage in liver and kidneys. After comprehensive laboratory testing and supportive care, the symptoms did not subside and treatment with complement C5 inhibitor eculizumab was started. Thereafter, the patient started to recover. The patient had pregnancy-induced aHUS. Earlier initiation of eculizumab treatment may potentially shorten and mitigate the disease and hypothetically decrease future health risks of preeclamptic women.
  • Burke, Orlaith; Benton, Samantha; Szafranski, Pawel; von Dadelszen, Peter; Buhimschi, S. Catalin; Cetin, Irene; Chappell, Lucy; Figueras, Francesc; Galindo, Alberto; Herraiz, Ignacio; Holzman, Claudia; Hubel, Carl; Knudsen, Ulla; Kronborg, Camilla; Laivuori, Hannele; Lapaire, Olav; McElrath, Thomas; Moertl, Manfred; Myers, Jenny; Ness, Roberta B.; Oliveira, Leandro; Olson, Gayle; Poston, Lucilla; Ris-Stalpers, Carrie; Roberts, James M.; Schalekamp-Timmermans, Sarah; Schlembach, Dietmar; Steegers, Eric; Stepan, Holger; Tsatsaris, Vassilis; van der Post, Joris A.; Verlohren, Stefan; Villa, Pia M.; Williams, David; Zeisler, Harald; Redman, Christopher W. G.; Staff, Anne Cathrine; Global Pregnancy Collaboration (2016)
    Background: A common challenge in medicine, exemplified in the analysis of biomarker data, is that large studies are needed for sufficient statistical power. Often, this may only be achievable by aggregating multiple cohorts. However, different studies may use disparate platforms for laboratory analysis, which can hinder merging. Methods: Using circulating placental growth factor (PIGF), a potential biomarker for hypertensive disorders of pregnancy (HDP) such as preeclampsia, as an example, we investigated how such issues can be overcome by inter-platform standardization and merging algorithms. We studied 16,462 pregnancies from 22 study cohorts. PIGF measurements (gestational age >= 20 weeks) analyzed on one of four platforms: R & Systems, Alere (R) Triage, Roche (R) Elecsys or Abbott (R) Architect, were available for 13,429 women. Two merging algorithms, using Z-Score and Multiple of Median transformations, were applied. Results: Best reference curves (BRC), based on merged, transformed PIGF measurements in uncomplicated pregnancy across six gestational age groups, were estimated. Identification of HDP by these PIGF-BRCS was compared to that of platform-specific curves. Conclusions: We demonstrate the feasibility of merging PIGF concentrations from different analytical platforms. Overall BRC identification of HDP performed at least as well as platform-specific curves. Our method can be extended to any set of biomarkers obtained from different laboratory platforms in any field. Merged biomarker data from multiple studies will improve statistical power and enlarge our understanding of the pathophysiology and management of medical syndromes. (C) 2015 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.
  • Wang, Jingwen; Skoog, Tiina; Einarsdottir, Elisabet; Kaartokallio, Tea; Laivuori, Hannele; Grauers, Anna; Gerdhem, Paul; Hytonen, Marjo; Lohi, Hannes; Kere, Juha; Jiao, Hong (2016)
    High-throughput sequencing using pooled DNA samples can facilitate genome-wide studies on rare and low-frequency variants in a large population. Some major questions concerning the pooling sequencing strategy are whether rare and low-frequency variants can be detected reliably, and whether estimated minor allele frequencies (MAFs) can represent the actual values obtained from individually genotyped samples. In this study, we evaluated MAF estimates using three variant detection tools with two sets of pooled whole exome sequencing (WES) and one set of pooled whole genome sequencing (WGS) data. Both GATK and Freebayes displayed high sensitivity, specificity and accuracy when detecting rare or low-frequency variants. For the WGS study, 56% of the low-frequency variants in Illumina array have identical MAFs and 26% have one allele difference between sequencing and individual genotyping data. The MAF estimates from WGS correlated well (r = 0.94) with those from Illumina arrays. The MAFs from the pooled WES data also showed high concordance (r = 0.88) with those from the individual genotyping data. In conclusion, the MAFs estimated from pooled DNA sequencing data reflect the MAFs in individually genotyped samples well. The pooling strategy can thus be a rapid and cost-effective approach for the initial screening in large-scale association studies.
  • Gu, Yuying; Lu, Jun; Li, Weiqin; Liu, Huikun; Wang, Leishen; Leng, Junhong; Li, Wei; Zhang, Shuang; Wang, Shuting; Tuomilehto, Jaakko; Yu, Zhijie; Yang, Xilin; Baccarelli, Andrea A.; Hou, Lifang; Hu, Gang (2019)
    Objectives: Either maternal gestational diabetes mellitus (GDM) or hypertensive disorder of pregnancy (HDP) is associated with an increased risk of obesity in the offspring. However, their joint associations with obesity in offspring remain unclear. We investigated the joint associations of maternal GDM and HDP with childhood overweight in offspring.Methods: We performed a large study in 1967 mother-child pairs. Maternal GDM was diagnosed according to the 1999 World Health Organization (WHO) criteria. HDP was defined as self-reported doctor-diagnosed hypertension or treatment of hypertension (including gestational hypertension, preeclampsia, sever preeclampsia or eclampsia) after 20 weeks of gestation on the questionnaire. Body mass index (BMI) for age Z-score and childhood overweight were evaluated according to WHO growth reference. We used the general linear models to compare children's Z score for BMI and logistic regression models to estimate odds ratios of childhood overweight according to maternal different status of GDM and HDP.Results: Offspring of mothers with both GDM and HDP had a higher BMI for age Z-score (0.63 vs. 0.03, P <0.001) than children born to normotensive and normoglycemic pregnancy. After adjustment for maternal and children's major confounding factors, joint GDM and HDP were associated with increased odds ratios of offspring's overweight compared with normotensive and normoglycemic pregnancy (2.97, 95% confidence intervals [CIs] 1.65–5.34) and GDM alone (2.06, 95% CIs 1.20–3.54), respectively. After additional adjustment for maternal pre-pregnancy BMI and gestational weight gain, joint maternal GDM, and HDP was still associated with an increased risk of offspring's overweight compared with the maternal normotensive, and normoglycemic group but became to have a borderline increased risk compared with the maternal GDM alone group.Conclusions: Maternal GDM alone or joint GDM and HDP were associated with increased ratios of offspring's overweight.
  • Kalapotharakos, Grigorios; Murtoniemi, Katja; Åkerström, Bo; Hämäläinen, Esa; Kajantie, Eero; Räikkönen, Katri; Villa, Pia; Laivuori, Hannele; Hansson, Stefan R. (2019)
    Women with established preeclampsia (PE) have increased plasma concentration of free fetal hemoglobin. We measured two hemoglobin scavenger system proteins, hemopexin (Hpx) and alpha-1 -microglobulin (A1M) in maternal plasma using enzyme-linked immunosorbent assay during the late second trimester of pregnancy in women with high and low risk of developing PE. In total 142 women were included in nested case-control study: 42 women diagnosed with PE and 100 controls (49 randomly selected high-risk and 51 low-risk controls). The concentration of plasma A1M in high-risk controls was higher compared to low-risk controls. Women with severe PE had higher plasma A1M levels compared to women with non-severe PE. In conclusion, the concentration of plasma A1M is increased in the late second trimester in high-risk controls, suggesting activation of endogenous protective system against oxidative stress.
  • Karjalainen, Liisa; Tikkanen, Minna; Rantanen, Kirsi; Laivuori, Hannele; Gissler, Mika; Ijäs, Petra (2019)
    BackgroundPregnancy-associated stroke is a rare but life-threatening event, with an estimated incidence of 30/100000 deliveries. Data on the risk of stroke recurrence and the risk of other adverse pregnancy outcomes are essential for adequate counselling and surveillance in subsequent pregnancies. The aim of this systematic review is to describe the implications of a pregnancy-associated stroke for the future health of these women.MethodsWe searched Ovid Medline, PubMed, Cochrane Library and CINAHL for articles published in 1980-2018. Articles including women with pregnancy-associated stroke and information on at least one of the following outcomes were included: 1) recurrence of stroke during subsequent pregnancy, 2) number and course of subsequent pregnancies and their outcomes and 3) subsequent cardiovascular health.ResultsTwelve articles were included in the review, with six providing information on subsequent pregnancies, four on subsequent maternal health and two on both. The included articles varied greatly in terms of study design, length of follow up and reported outcomes. We found 252 women with pregnancy-associated stroke for whom the outcomes of interest were reported: 135 women with information on subsequent pregnancies and 123 women with information on future health. In total, 55 pregnancies after stroke were found. In the majority of studies, the incidence of pregnancy complications was comparable to that of the general population. The risk of stroke recurrence during pregnancy was 2%. Data on subsequent health of these women were limited, and the quality of the data varied between the studies.ConclusionsData on subsequent pregnancies and health of women with a history of pregnancy-associated stroke are limited. Further research on this topic is essential for adequate counselling and secondary prevention.
  • Eriksson, Johan G.; Venojarvi, Mika; Osmond, Clive (2016)
    Several noncommunicable diseases have their origins in early developmental phases. One factor possibly explaining the association between early growth and later health could be adipocyte function. The objective of this study was to assess the association between the adipocytokine chemerin and early growth and later health. 1074 participants from Helsinki Birth Cohort Study born 19341944 with information on prenatal and childhood growth participated. Metabolic outcomes include glucose tolerance, adiposity, and chemerin concentration. Mean chemerin concentrations were 5.0 ng/mL higher in women than in men (95% CI 2.7 to 7.2, P <0.001). The strongest correlate of chemerin concentration was adult waist circumference and body fat percentage (r = 0.22, P <0.001 and r= 0.21, P <0.001, resp.). After adjustment for body fat percentage, chemerin concentration was 5.4 ng/mL lower in subjects with type 2 diabetes than in those with normal glucose tolerance (-0.2 to 10.9, P = 0.06). It was 3.0 ng/mL higher in those with metabolic syndrome than in those without (0.6 to 5.3, P = 0.01). No measure of early growth was associated with chemerin concentration. Our findings do not support a role for chemerin in linking early growth with later metabolic health.
  • Toijonen, Anna; Heinonen, Seppo; Gissler, Mika; Macharey, Georg (2021)
    Purpose To assess the risk factors for adverse outcomes in attempted vaginal preterm breech deliveries. Methods A retrospective case-control study, including 2312 preterm breech deliveries (24 + 0 to 36 + 6 gestational weeks) from 2004 to 2018 in Finland. The preterm breech fetuses with adverse outcomes born vaginally or by emergency cesarean section were compared with the fetuses without adverse outcomes with the same gestational age. A multivariable logistic regression analysis was used to calculate the risk factors for adverse outcomes (umbilical arterial pH below 7, 5-min Apgar score below 4, intrapartum stillbirth and neonatal death <28 days of age). Results Adverse outcome in vaginal preterm breech delivery was associated with maternal obesity (aOR 32.19, CI 2.97-348.65), smoking (aOR 2.29, CI 1.12-4.72), congenital anomalies (aOR 4.50, 1.56-12.96), preterm premature rupture of membranes (aOR 1.87, CI 1.00-3.49), oligohydramnios (28-32 weeks of gestation: aOR 6.50, CI 2.00-21.11, 33-36 weeks of gestation: aOR 19.06, CI 7.15-50.85), epidural anesthesia in vaginal birth (aOR 2.44, CI 1.19-5.01), and fetal growth below the second standard deviation (28-32 weeks of gestation: aOR 5.89, CI 1.00-34.74, 33-36 weeks of gestation: aOR 12.27, CI 2.81-53.66). Conclusion The study shows that for each subcategory of preterm birth, there are different risk factors for adverse neonatal outcomes in planned vaginal breech delivery. Due to the extraordinary increased risk of adverse outcomes, we would recommend a planned cesarean section in very preterm breech presentation (28 + 0 to 32 + 6 weeks) with severe maternal obesity, oligohydramnios, or fetal growth restriction and in moderate to late preterm breech presentation (33 + 0 to 36 + 6 weeks) with oligohydramnios or fetal growth restriction.
  • Aracic, Nada; Roje, Damir; Jakus, Ivana Alujevic; Bakotin, Marinela; Stefanovic, Vedran (2016)
    Purpose: To assess the distribution of births and spontaneous abortions, first-trimester abortion (FTA) and mid-trimester abortion (MTA), in untreated (n=128) and low molecular weight heparin (LMWH) treated pregnancies (n=50) of the same women with inherited thrombophilias and adverse pregnancy outcome (APO) in previous pregnancies. We particularly investigated the impact of LMWH on reducing the pregnancy complications in two thrombophilia types, "Conventional" and "Novel". Materials and Methods: 50 women with inherited thrombophilia (26 Conventional and 24 Novel) and APO in previous pregnancies were included in the study. Conventional group included factor V Leiden (FVL), prothrombin G20210A (PT) mutations and antithrombin (AT), protein S (PS), and protein C (PC) deficiency, while the Novel group included methylentetrahydrofolate-reductase (MTHFR), plasminogen activator inhibitor-1 (PAI-1), and angiotensin converting enzyme (ACE) polymorphism. APO was defined as one of the following: preterm birth (PTB), fetal growth restriction (FGR), preeclampsia (PE), intrauterine fetal death (IUFD), placental abruption (PA) and deep venous thrombosis (DVT). Results: There was no difference in distribution of births and spontaneous abortions between Conventional and Novel thrombophilia in untreated pregnancies (chi(2)=2.7; p=0.100) and LMWH treated pregnancies (chi(2)=0.442; p=0.506). In untreaed pregnancies thrombophilia type did not have any impact on the frequency of FTA and MTA (chi(2)=0.14; p=0.711). In birth-ended pregnancies LMWH treatement reduced the incidence of IUFD (p=0.011) in Conventional and FGR, IUFD, and PTB in Novel thrombophilia group. Conclusion: The equal impact of two thrombophilia types on the pregnancy outcomes and a more favorable effect of LMWH therapy on pregnancy complications in Novel thrombophilia group point the need for Novel thrombophilias screening and the future studies on this issue should be recommended.
  • Reichhardt, Martin Parnov; Jarva, Hanna; Lokki, Anna Inkeri; Laivuori, Hannele; Vuorela, Piia; Loimaranta, Vuokko; Glasner, Andreas; Siwetz, Monika; Huppertz, Berthold; Meri, Seppo; FINNPEC Study Grp (2016)
    Pre-eclampsia is a leading cause of maternal and perinatal morbidity and mortality worldwide. The etiology is not clear, but an immune attack towards components of placenta or fetus has been indicated. This involves activation of the complement system in the placenta. We have previously described the presence of the complement-regulating protein salivary scavenger and agglutinin (SALSA) in amniotic fluid. In this study we investigated the potential role of SALSA in pregnancy by analyzing its presence in amniotic fluid and placental tissue during healthy and complicated pregnancies. SALSA levels in amniotic fluid increased during pregnancy. Before 20 weeks of gestation the levels were slightly higher in patients who later developed pre-eclampsia than in gestation age-matched controls. In the placenta of pre-eclamptic patients syncytial damage is often followed by the formation of fibrinoid structures. SALSA was found clustered into these fibrinoid structures in partial co-localization with complement C1q and fibronectin. In vitro analysis showed direct protein binding of SALSA to fibronectin. SALSA binds also to fibrin/fibrinogen but did not interfere with the blood clotting process in vitro. Thus, in addition to antimicrobial defense and epithelial differentiation, the data presented here suggest that SALSA, together with fibronectin and C1q, may be involved in the containment of injured placental structures into fibrinoids.
  • 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.