Geburtshilfe Frauenheilkd 2011; 71(9): 773-778
DOI: 10.1055/s-0031-1280229
Original Article

© Georg Thieme Verlag KG Stuttgart · New York

Predictive Value of Plasma Total Carnitine, Arginine, Asymmetric Dimethylarginine and Ischemia-modified Albumin Levels and Their Combined Use in the Early Detection of Preeclampsia

Bedeutung von Plasma-Carnitin, Arginin, asymmetrischem Dimethylarginin und Ischämie-modifiziertem Albumin für die Prognose und deren Einsatz in der Früherkennung von PräeklampsieM. A. Osmanağaoğlu1 , S. Caner Karahan2 , T. Aran1 , S. Güven1 , C. Kart1 , İ. Pekgöz1 , A. Menteşe2 , H. Bozkaya1
  • 1Department of Obstetrics and Gynecology, Karadeniz Technical University, School of Medicine, Trabzon, Turkey
  • 2Department of Biochemistry, Karadeniz Technical University, School of Medicine, Trabzon, Turkey
Further Information

Publication History

received 30.6.2011 revised 22.7.2011

accepted 10.8.2011

Publication Date:
30 September 2011 (online)

Abstract

Purpose: Aim of the study was to investigate serum levels of total carnitine, arginine, asymmetric dimethylarginine (ADMA) and ischemia-modified albumin (IMA) and their combined use for the early detection of preeclampsia. Materials and Methods: The study group, which included normal pregnancies, consisted of a total of 44 singleton pregnant women (gestational age: between 6 and 12 weeks), divided into a preeclampsia group (n = 22) and a control group (n = 22). Results: When the serum levels of both groups in the 6th and 12th week of gestation were compared with levels between the 21st and 35th week of gestation, total carnitine, ADMA, IMA levels were increased; L-arginine levels were decreased in the preeclampsia group. Using a total carnitine level of ≤ 3.62 nmol/ml as a cut-off value, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 68, 64, 65 and 64 %; using an ADMA level of ≤ 518.70 ng/ml as a cut-off value, the sensitivity, specificity, PPV and NPV were 82, 32, 55 and 64 %; using an L-arginine level of ≤ 161.23 nmol/ml as a cut-off value, the sensitivity, specificity, PPV and NPV were 45, 73, 62, 57 %; using an IMA level of > 0.82 as a cut-off value, the sensitivity, specificity, PPV and NPV were 45, 77, 64 and 57 %, respectively. When all parameters were taken together to predict preeclampsia, the sensitivity, specificity, PPV and NPV were 9, 100, 100 and 52 %, respectively. Conclusion: Although the sensitivity of ADMA levels was found to be higher in individual measurements, there is still no independent placental ischemia factor which can predict preeclampsia.

Zusammenfassung

Fragestellung: Ziel der Studie war es, die Serumkonzentrationen von Plasma-Carnitin, Arginin, asymmetrischem Dimethylarginin (ADMA) und Ischämie-modifiziertem Albumin (IMA) zu untersuchen sowie die Kombination dieser Werte als potenzielle Indikatoren zur Früherkennung von Präeklampsie. Material und Methoden: Es wurden 44 schwangere Frauen (Einlingsschwangerschaften, Gestationsalter zwischen 6 und 12 Wochen) untersucht: Präeklampsiegruppe (n = 22), Kontrollgruppe (n = 22). Ergebnisse: Serumkonzentrationen in der 6. und 12. Gestationswoche wurden mit Serumkonzentrationen in der 21. und 35. Gestationswoche in beiden Gruppen verglichen. Carnitin-, ADMA-, und IMA-Konzentrationen waren erhöht; L-Arginin-Konzentrationen in der Präeklampsiegruppe waren verringert. Bei einem Carnitin-Wert von ≤ 3,62 nmol/ml als Cut-off-Wert war die Sensitivität, Spezifität, PPV und NPV 68, 64, 65 und 64 %, bei einem ADMA-Wert von ≤ 518,70 ng/ml als Cut-off-Wert betrugen die Sensitivität, Spezifität, PPV und NPV 82, 32, 55 und 64 %, bei einem L-Arginin-Wert von ≤ 161,23 als Cut-off-Wert betrugen die Sensitivität, Spezifität, PPV und NPV 45, 73, 62 und 57 %, bei einem IMA-Wert von > 0,82 als Cut-off-Wert lagen die Sensitivität, Spezifität, PPV und NPV bei 45, 77, 64 und 57 %. Wurden alle Parameter zusammen betrachtet, betrugen die Sensitivität, Spezifität, PPV und NPV 9, 100, 100 und 52 %. Schlussfolgerung: Obwohl die Sensitivität der ADMA-Konzentration höher war, gibt es dennoch keinen unabhängigen Ischämiefaktor, der als Indikator zur Vorhersage von Präeklampsie dienen könnte.

References

  • 1 Sattar N, Gaw A, Packard C J et al. Potential pathogenic roles of aberrant lipoprotein and fatty acid metabolism in pre-eclampsia.  Br J Obstet Gynaecol. 1996;  103 614-620
  • 2 Thiele I G, Niezen-Koning K E, van Gennip A H et al. Increased plasma carnitine concentrations in preeclampsia.  Obstet Gynecol. 2004;  103 876-880
  • 3 Fickling S A, Williams D, Vallance P et al. Plasma concentrations of endogenous inhibitor of nitric oxide synthesis in normal pregnancy and pre-eclampsia.  Lancet. 1993;  342 242-243
  • 4 Holden D P, Fickling S A, Whitley G S et al. Plasma concentrations of asymmetric dimethylarginine, a natural inhibitor of nitric oxide synthase, in normal pregnancy and preeclampsia.  Am J Obstet Gynecol. 1998;  178 551-556
  • 5 Üstün Y, Engin-Üstün Y, Öztürk O et al. Ischemia-modified albumin as an oxidative stress marker in preeclampsia.  J Matern Fetal Neonatal Med. 2011;  24 418-421
  • 6 Hubel C A. Oxidative stress in the pathogenesis of preeclampsia.  Proc Soc Exp Biol Med. 1999;  222 222-235
  • 7 Van Rijn B B, Franx A, Sikkema J M et al. Ischemia modified albumin in normal pregnancy and preeclampsia.  Hypertens Pregnancy. 2008;  27 159-167
  • 8 Iacovidou N, Briana D D, Boutsikou M et al. Cord blood ischemia-modified albumin levels in normal and intrauterine growth restricted pregnancies.  Mediators Inflamm. 2008;  2008 523081
  • 9 Guven S, Alver A, Menteşe A et al. The novel ischemia marker ‘ischemia-modified albumin is increased in normal pregnancies.  Acta Obstet Gynecol Scand. 2009;  88 479-482
  • 10 Bar-Or D, Lau E, Winkler J V. A novel assay for cobalt-albumin binding and its potential as a marker for myocardial ischemia – a preliminary report.  J Emerg Med. 2000;  19 311-315
  • 11 Tanphaichitr V, Leelahagul P. Carnitine metabolism and human carnitine deficiency.  Nutrition. 1993;  3 246-254
  • 12 Bargen-Lockner C, Hahn P, Wittman B. Plasma carnitine in pregnancy.  Am J Obstetr Gyn. 1981;  140 412-414
  • 13 Scholte H R, Stinis J T, Jennekens F G I. Low carnitine levels in serum of pregnant women.  N Engl J Med. 1979;  299 1079-1080
  • 14 Savvidou M, Hingorani A, Tsikas D et al. Endothelial dysfunction and raised plasma concentrations of asymmetric dimethylarginine in pregnant women who subsequently develop preeclampsia.  Lancet. 2003;  361 1511-1517
  • 15 Tran Cam T L, Fox M F, Vallance P et al. Chromosomal localization, gene structure and expression pattern of DDAH1: comparison with DDAH2 and implications for evolutionary origins.  Genomics. 2000;  68 101-105
  • 16 Leiper J, MacAllister R, Whitley G et al. Identification of two human dimethylarginine dimethylaminohydrolases with distinct tissue distributions and homology to microbial arginine deiminases.  Biochem J. 1999;  343 209-214
  • 17 Kim Y J, Park H S, Lee H Y et al. Reduced L-arginine level and decreased placental eNOS activity in preeclampsia.  Placenta. 2006;  27 438-444
  • 18 Noris M, Todeschini M, Cassis P et al. L-arginine depletion in preeclampsia orients nitric oxide synthase toward oxidant species.  Hypertension. 2004;  43 614-622

Dr. Mehmet Osmanağaoğlu

Department of Obstetrics and Gynecology
Karadeniz Technical University
School of Medicine

61080 Trabzon

Turkey

Email: drmaosmanaga@gmail.com