Browsing by Subject "FETAL"

Sort by: Order: Results:

Now showing items 1-16 of 16
  • 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.
  • Wehkalampi, Karoliina; Muurinen, Mari; Wirta, Sara Bruce; Hannula-Jouppi, Katariina; Hovi, Petteri; Järvenpää, Anna-Liisa; Eriksson, Johan G.; Andersson, Sture; Kere, Juha; Kajantie, Eero (2013)
  • Seikku, Laura; Stefanovic, Vedran; Rahkonen, Petri; Teramo, Kari; Paavonen, Jorma; Tikkanen, Minna; Rahkonen, Leena (2019)
    Objective: Erythropoietin - a hormone regulating erythropoiesis - is a biomarker of chronic fetal hypoxia. High erythropoietin levels in fetal plasma and amniotic fluid are associated with increased risk of adverse neonatal outcome. Since the risk of perinatal morbidity and mortality is increased in pregnancies beyond 41 gestational weeks, we evaluated erythropoietin levels in amniotic fluid and umbilical cord serum in apparently low-risk term (>= 37 gestational weeks) and prolonged pregnancies (>= 41 gestational weeks) with labor induction. Study design: This prospective cohort study comprised 93 singleton pregnancies at 37(+0)-42(+1) gestational weeks, of which prolonged pregnancies numbered 63 (67.7%). Amniotic fluid samples were collected at time of labor induction by amniotomy. Umbilical cord blood samples for evaluation of pH, base excess, and umbilical cord serum erythropoietin were collected at birth. Erythropoietin levels were measured by immunochemiluminometric assay. Normal value of amniotic fluid erythropoietin level was defined as = 27 IU/L. Normal umbilical cord serum erythropoietin was defined as <40 IU/L. Data on maternal pregnancy and delivery characteristics and short-term neonatal outcomes such as Apgar score were obtained from the hospital charts. Associations were calculated using Spearman's rank correlation coefficient. The Chi-square test, Fisher's exact test and the Mann-Whitney U test were utilized to determine differences in the study groups. Results: Amniotic fluid erythropoietin levels correlated with gestational age (r = 0.261, p = 0.012) and were higher among prolonged pregnancies as compared to term pregnancies (p = 0.005). There were 78 (83.9%) vaginal deliveries, and among these erythropoietin levels in amniotic fluid correlated with the levels in umbilical cord serum (r = 0.513, p <0.000). Umbilical cord serum erythropoietin levels correlated with gestational age among vaginal deliveries (r = 0.250, p = 0.027). Erythropoietin levels in amniotic fluid and umbilical cord serum did not correlate with umbilical artery pH or base excess, or other adverse pregnancy outcome. Conclusions: In vaginal deliveries erythropoietin levels in amniotic fluid correlated with the levels in umbilical cord serum. Erythropoietin levels correlated with gestational age, probably due to weakening placental function and relative hypoxemia occurring in advanced gestation. However, in this relatively low-risk study population erythropoietin was not related to adverse delivery outcome. (C) 2018 Elsevier B.V. All rights reserved.
  • Jelenkovic, Aline; Mikkonen, Janne; Martikainen, Pekka; Latvala, Antti; Yokoyama, Yoshie; Sund, Reijo; Vuoksimaa, Eero; Rebato, Esther; Sung, Joohon; Kim, Jina; Lee, Jooyeon; Lee, Sooji; Stazi, Maria A.; Fagnani, Corrado; Brescianini, Sonia; Derom, Catherine A.; Vlietinck, Robert F.; Loos, Ruth J. F.; Krueger, Robert F.; Mcgue, Matt; Pahlen, Shandell; Nelson, Tracy L.; Whitfield, Keith E.; Brandt, Ingunn; Nilsen, Thomas S.; Harris, Jennifer R.; Cutler, Tessa L.; Hopper, John L.; Tarnoki, Adam D.; Tarnoki, David L.; Sorensen, Thorkild I. A.; Kaprio, Jaakko; Silventoinen, Karri (2018)
    Background There is evidence that birth weight is positively associated with education, but it remains unclear whether this association is explained by familial environmental factors, genetic factors or the intrauterine environment. We analysed the association between birth weight and educational years within twin pairs, which controls for genetic factors and the environment shared between co-twins. Methods The data were derived from nine twin cohorts in eight countries including 6116 complete twin pairs. The association between birth weight and educational attainment was analysed both between individuals and within pairs using linear regression analyses. Results In between-individual analyses, birth weight was not associated with educational years. Within-pairs analyses revealed positive but modest associations for some sex, zygosity and birth year groups. The greatest association was found in dizygotic (DZ) men (0.65 educational years/kg birth weight, p=0.006); smaller effects of 0.3 educational years/kg birth weight were found within monozygotic (MZ) twins of both sexes and opposite-sex DZ twins. The magnitude of the associations differed by birth year in MZ women and opposite-sex DZ twins, showing a positive association in the 1915-1959 birth cohort but no association in the 1960-1984 birth cohort. Conclusion Although associations are weak and somewhat inconsistent, our results suggest that intrauterine environment may play a role when explaining the association between birth weight and educational attainment.
  • Czamara, Darina; Dieckmann, Linda; Roeh, Simone; Kraemer, Sarah; Rancourt, Rebecca C.; Sammallahti, Sara; Kajantie, Eero; Laivuori, Hannele; Eriksson, Johan G.; Räikkönen, Katri; Henrich, Wolfgang; Plagemann, Andreas; Binder, Elisabeth B.; Braun, Thorsten; Entringer, Sonja (2021)
    Background Glucocorticoids (GCs) play a pivotal role in fetal programming. Antenatal treatment with synthetic GCs (sGCs) in individuals in danger of preterm labor is common practice. Adverse short- and long-term effects of antenatal sGCs have been reported, but their effects on placental epigenetic characteristics have never been systematically studied in humans. Results We tested the association between exposure to the sGC betamethasone (BET) and placental DNA methylation (DNAm) in 52 exposed cases and 84 gestational-age-matched controls. We fine-mapped associated loci using targeted bisulfite sequencing. The association of placental DNAm with gene expression and co-expression analysis on implicated genes was performed in an independent cohort including 494 placentas. Exposure to BET was significantly associated with lower placenta DNAm at an enhancer of FKBP5. FKBP5 (FK506-binding protein 51) is a co-chaperone that modulates glucocorticoid receptor activity. Lower DNAm at this enhancer site was associated with higher expression of FKBP5 and a co-expressed gene module. This module is enriched for genes associated with preeclampsia and involved in inflammation and immune response. Conclusions Our findings suggest that BET exposure during pregnancy associates with few but lasting changes in placental DNAm and may promote a gene expression profile associated with placental dysfunction and increased inflammation. This may represent a pathway mediating GC-associated negative long-term consequences and health outcomes in offspring.
  • Summanen, Milla; Seikku, Laura; Rahkonen, Petri; Stefanovic, Vedran; Teramo, Kari; Andersson, Sture; Kaila, Kai; Rahkonen, Leena (2017)
    Background: Birth asphyxia, estimated to account for a million neonatal deaths annually, can cause a wide variety of neurodevelopmental impairments. There is a need to develop new, swift methods to identify those neonates who would benefit from neuroprotective treatments such as hypothermia. Objectives: To examine the utility of cord serum copeptin, a stable byproduct of arginine vasopressin release, as a biomarker of birth asphyxia based on a comparison with 2 biomarkers of hypoxia and brain trauma: erythropoietin and S100B. Methods: The study population consisted of 140 singleton, term neonates: 113 controls and 27 with birth asphyxia (2/3 criteria met: umbilical artery pH
  • Miettinen, Helena E.; Rono, Kristiina; Koivusalo, Saila B.; Eriksson, Johan G.; Gylling, Helena (2018)
    Background and aims: Impaired glucose metabolism during pregnancy may associate with changes in fetal cholesterol metabolism. We investigated if gestational diabetes mellitus (GDM) affects newborn cholesterol metabolism as determined by cord blood squalene and non-cholesterol sterols. Furthermore, we examined potential correlations between cord blood and maternal serum non-cholesterol sterols. Methods: Pregnant women at risk for GDM (BMI>30 kg/m(2)) were enrolled from maternity clinics in Finland. GDM was determined from the results of an oral glucose tolerance test. Serum samples were taken in the third trimester of pregnancy, and cord blood samples collected from their newborns at birth. Squalene and non-cholesterol sterols were analyzed from serum and cord blood by gas liquid chromatography. All women with GDM were in good glycaemic control. Results: The ratios of squalene and non-cholesterol sterols to cholesterol (100 x mu mol/mmol of cholesterol) in cord blood did not differ between the infants born to mothers with GDM (n = 15) or mothers with normal glucose tolerance (n = 13). The ratios of sitosterol and campesterol to cholesterol in the cord blood correlated with the corresponding maternal serum ratios (r = 0.70, p <0.0001) in both groups. Conclusions: In obese women under good glycaemic control, GDM did not affect newborn cholesterol metabolism. Cord blood sitosterol and campesterol ratios to cholesterol correlated with the corresponding maternal serum ratios thus potentially reflecting maternal-fetal cholesterol transport. (C) 2018 Elsevier B.V. All rights reserved.
  • Kaartokallio, Tea; Wang, Jingwen; Heinonen, Seppo Tapani; Kajantie, Eero; Kivinen, Katja; Pouta, Anneli; Gerdhem, Paul; Jiao, Hong; Kere, Juha; Laivuori, Hannele (2016)
    Pre-eclampsia is a common pregnancy disorder that is a major cause for maternal and perinatal mortality and morbidity. Variants predisposing to pre-eclampsia might be under negative evolutionary selection that is likely to keep their population frequencies low. We exome sequenced samples from a hundred Finnish pre-eclamptic women in pools of ten to screen for low-frequency, large-effect risk variants for pre-eclampsia. After filtering and additional genotyping steps, we selected 28 low-frequency missense, nonsense and splice site variants that were enriched in the pre-eclampsia pools compared to reference data, and genotyped the variants in 1353 pre-eclamptic and 699 non-pre-eclamptic women to test the association of them with pre-eclampsia and quantitative traits relevant for the disease. Genotypes from the SISu project (n = 6118 exome sequenced Finnish samples) were included in the binary trait association analysis as a population reference to increase statistical power. In these analyses, none of the variants tested reached genome-wide significance. In conclusion, the genetic risk for pre-eclampsia is likely complex even in a population isolate like Finland, and larger sample sizes will be necessary to detect risk variants.
  • Qingdao Diabet Prevention Program; Ning, Feng; Ren, Jie; Qiao, Qing (2019)
    This study examined the association between famine exposure in early life and the risk of metabolic syndrome (MetS) in adulthood during the 1959-1961 Chinese Famine. Two cross-sectional surveys involving randomly selected Chinese adults aged 35-74 years in the Qingdao area were conducted. A total of 9,588 individuals were grouped into four birth cohorts of unexposed (born between January 1, 1962, and December 31, 1975), fetal-exposed (born between January 1, 1959, and December 31, 1961), childhood-exposed (born between January 1, 1949, and December 31, 1958), and adolescence/adult-exposed cohorts (born between January 1, 1931, and December 31, 1948). We assessed the prevalence rate of MetS in relation to famine exposure according to three definitions of MetS by the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III), International Diabetes Federation (IDF), and China Diabetes Society (CDS). According to the CDS criterion, the prevalence rates of MetS were 17.8%, 25.7%, 31.1%, and 45.3% in the unexposed, fetal-, childhood-, and adolescence/adult-exposed cohorts, respectively (P
  • Steinthorsdottir, Valgerdur; McGinnis, Ralph; Williams, Nicholas O.; Stefansdottir, Lilja; Thorleifsson, Gudmar; Shooter, Scott; Fadista, Joao; Sigurdsson, Jon K.; Auro, Kirsi M.; Berezina, Galina; Borges, Maria-Carolina; Bumpstead, Suzannah; Bybjerg-Grauholm, Jonas; Colgiu, Irina; Dolby, Vivien A.; Dudbridge, Frank; Engel, Stephanie M.; Franklin, Christopher S.; Frigge, Michael L.; Frisbaek, Yr; Geirsson, Reynir T.; Geller, Frank; Gretasdottir, Solveig; Gudbjartsson, Daniel F.; Harmon, Quaker; Hougaard, David Michael; Hegay, Tatyana; Helgadottir, Anna; Hjartardottir, Sigrun; Jääskeläinen, Tiina; Johannsdottir, Hrefna; Jonsdottir, Ingileif; Juliusdottir, Thorhildur; Kalsheker, Noor; Kasimov, Abdumadjit; Kemp, John P.; Kivinen, Katja; Klungsøyr, Kari; Lee, Wai K.; Melbye, Mads; Miedzybrodska, Zosia; Moffett, Ashley; Najmutdinova, Dilbar; Nishanova, Firuza; Olafsdottir, Thorunn; Perola, Markus; FINNPEC Consortium; Laivuori, Hannele; Heinonen, Seppo; Kajantie, Eero; Kere, Juha; Kivinen, Katja; Pouta, Anneli (2020)
    Preeclampsia is a serious complication of pregnancy, affecting both maternal and fetal health. In genome-wide association meta-analysis of European and Central Asian mothers, we identify sequence variants that associate with preeclampsia in the maternal genome at ZNF831/20q13 and FTO/16q12. These are previously established variants for blood pressure (BP) and the FTO variant has also been associated with body mass index (BMI). Further analysis of BP variants establishes that variants at MECOM/3q26, FGF5/4q21 and SH2B3/12q24 also associate with preeclampsia through the maternal genome. We further show that a polygenic risk score for hypertension associates with preeclampsia. However, comparison with gestational hypertension indicates that additional factors modify the risk of preeclampsia. Studies to identify maternal variants associated with preeclampsia have been limited by sample size. Here, the authors meta-analyze eight GWAS of 9,515 preeclamptic women, identifying five variants associated with preeclampsia and showing that genetic predisposition to hypertension is a major risk factor for preeclampsia.
  • Doerner, Julia; Rodriguez, Verena Martinez; Ziegler, Ricarda; Roehrig, Theresa; Cochran, Rebecca S.; Goetz, Ronni M.; Levin, Mark D.; Pihlajoki, Marjut; Heikinheimo, Markku; Wilson, David B. (2017)
    As certain strains of mice age, hyperplastic lesions resembling gonadal tissue accumulate beneath the adrenal capsule. Gonadectomy (GDX) accelerates this heterotopic differentiation, resulting in the formation of wedge-shaped adrenocortical neoplasms that produce sex steroids. Stem/progenitor cells that reside in the adrenal capsule and retain properties of the adrenogonadal primordium are thought to be the source of this heterotopic tissue. Here, we demonstrate that GLI1(+) progenitors in the adrenal capsule give rise to gonadal-like cells that accumulate in the subcapsular region. A tamoxifen-inducible Cre driver (Glil-creER(T2)) and two reporters (R26R-lacZ, R26R-confetti) were used to track the fate of GLI1(+) cells in the adrenal glands of B6D2F2 mice, a strain that develops both GDX-induced adrenocortical neoplasms and age-dependent subcapsular cell hyperplasia. In gonadectomized B6D2F2 mice GLI1(+) progenitors contributed to long-lived adrenal capsule cells and to adrenocortical neoplasms that expressed Gata4 and Foxl2, two prototypical gonadal markers. Pdgfra, a gene expressed in adrenocortical stromal cells, was upregulated in the GDX-induced neoplasms. In aged non-gonadectomized B6D2F2 mice GLI1(+) progenitors gave rise to patches of subcapsular cell hyperplasia. Treatment with GANT61, a small-molecule GLI antagonist, attenuated the upregulation of gonadal-like markers (Gata4, Foxl2) in response to GDX. These findings support the premise that GLI1(+) progenitor cells in the adrenal capsule of the adult mouse give rise to heterotopic tissue. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
  • Kanninen, Liisa K.; Porola, Pauliina; Niklander, Johanna; Malinen, Melina M.; Corlu, Anne; Guguen-Guillouzo, Christiane; Urtti, Arto; Yliperttula, Marjo L.; Lou, Yan-Ru (2016)
    Human hepatocytes are extensively needed in drug discovery and development. Stem cell-derived hepatocytes are expected to be an improved and continuous model of human liver to study drug candidates. Generation of endoderm-derived hepatocytes from human pluripotent stem cells (hPSCs), including human embryonic stem cells and induced pluripotent stem cells, is a complex, challenging process requiring specific signals from soluble factors and insoluble matrices at each developmental stage. In this study, we used human liver progenitor HepaRG-derived acellular matrix (ACM) as a hepatic progenitor-specific matrix to induce hepatic commitment of hPSC-derived definitive endoderm (DE) cells. The DE cells showed much better attachment to the HepaRG ACM than other matrices tested and then differentiated towards hepatic cells, which expressed hepatocyte-specific makers. We demonstrate that Matrigel overlay induced hepatocyte phenotype and inhibited biliary epithelial differentiation in two hPSC lines studied. In conclusion, our study demonstrates that the HepaRG ACM, a hepatic progenitor-specific matrix, plays an important role in the hepatic differentiation of hPSCs. (C) 2016 Elsevier Inc. All rights reserved.
  • Hauta-alus, Helena H.; Kajantie, Eero; Holmlund-Suila, Elisa M.; Rosendahl, Jenni; Valkama, Saara M.; Enlund-Cerullo, Maria; Helve, Otto M.; Hytinantti, Timo K.; Viljakainen, Heli; Andersson, Sture; Mäkitie, Outi (2019)
    Context: The relationship of maternal and infant 25-hydroxyvitamin D concentration [25(OH)D] with infant growth is unclear. Objective: Our objective was to explore whether 25(OH)D in pregnancy, umbilical cord blood (UCB), or in infancy was associated with infant growth. Design: This study involved 798 healthy infants and their mothers in Finland. We assessed 25(OH)D during pregnancy, from UCB at birth, and from the infant at the age of 12 months. Main Outcome Measures: Infant length, weight, length-adjusted weight, and head circumference at 6 and 12 months and midupper-arm circumference at 12 months. Results: Of the mothers and infants, 96% and 99% were vitamin D sufficient [25(OH)D >= 50 nmol/L], respectively. Mothers with pregnancy 25(OH)D >125 nmol/L had the shortest, lightest (in weight), and thinnest (in length-adjusted weight) infants at 6 months (P for all <0.05). For each 10 nmol/L higher UCB 25(OH)D, the infants were 0.03 SD score (SDS) shorter at 6 months (95% CI -0.05 to -0.01), adjusted for birth size, infant 25(OH)D, and parental height. Higher UCB 25(OH)D associated with smaller head circumference at 6 and 12 months (P for all 125 nmol/L had the thinnest infants at 12 months (P = 0.021). For each 10 nmol/L higher infant 25(OH)D, the infants were 0.03 SDS lighter (-0.05 to -0.01) and 0.03 SDS thinner (-0.05 to 0.00) at 12 months. Conclusions: Our results suggest that high pregnancy, cord blood, and infant vitamin D concentration may have disadvantageous effects on infant growth.
  • Stefanovic, Vedran; Andersson, Sture; Vento, Maximo (2019)
    Spontaneous preterm birth (PTB) is one of the major complications of pregnancy and the main cause of neonatal mortality and morbidity. Despite the efforts devoted to the understanding of this obstetrical syndrome and improved medical care, there has been a tendency for the PTB rate to increase in the last decades globally. The costs of the screening for spontaneous PTB, its management, and treatment of the sequelae represent a major burden to the health service economy of high-income countries. In this scenario, it has been widely acknowledged that oxidative stress (OS) plays an important role in the pathogenicity of human disease in wide range of areas of medicine. There is an emerging evidence that an imbalance between pro-and-antioxidants may be associated with spontaneous PTB. However, there are still many controversies on the mechanisms by which OS are involved in the pathogenesis of prematurity. Moreover, the crucial question whether the OS is the cause or consequence of the disease is yet to be answered. The purpose of this article is to briefly summarize the current knowledge and controversies on oxidative stress-related spontaneous PTB and to give a critical approach on future perspectives on this topic as a classical example of translational medicine. Placenta-mediated pregnancy adverse outcome associated with OS leading to iatrogenic PTB (e.g. pre-eclampsia, intrauterine growth restriction, gestational diabetes) will not be discussed.
  • Högberg, Ulf; Winbo, Jenny; Fellman, Vineta (2019)
    Abstract Aim This population-based study assessed the incidence of rickets in infants up to age of one born in Sweden from 1997-2014. We also examined maternal and perinatal factors and co-morbidity. Methods We used Swedish National Board of Health and Welfare registers and data from Statistics Sweden. The outcome measure was an International Classification of Diseases, Tenth Revision, code for rickets. Results There were 273 cases of rickets, with an incidence of 14.7 per 100,000 and a 10-fold incidence increase between 1997-2014. The majority (78.4%) were born preterm, half were small-for-gestational age (SGA) (birthweight
  • Partanen, Eino; Kujala, Teija; Tervaniemi, Mari; Huotilainen, Minna (2013)
    We investigated the neural correlates induced by prenatal exposure to melodies using brains' event-related potentials (ERPs). During the last trimester of pregnancy, the mothers in the learning group played the ‘Twinkle twinkle little star’ -melody 5 times per week. After birth and again at the age of 4 months, we played the infants a modified melody in which some of the notes were changed while ERPs to unchanged and changed notes were recorded. The ERPs were also recorded from a control group, who received no prenatal stimulation. Both at birth and at the age of 4 months, infants in the learning group had stronger ERPs to the unchanged notes than the control group. Furthermore, the ERP amplitudes to the changed and unchanged notes at birth were correlated with the amount of prenatal exposure. Our results show that extensive prenatal exposure to a melody induces neural representations that last for several months.