American Journal of Obstetrics & Gynecology
Volume 200, Issue 2 , Pages 151.e1-151.e9 , February 2009

Inherited thrombophilia and preeclampsia within a multicenter cohort: the Montreal Preeclampsia Study

Presented in part at the 27th Annual Meeting of the Society for Maternal–Fetal Medicine, San Francisco, CA, Feb. 6-9, 2007, and in part at the 21st Congress of the International Society on Thrombosis and Hemostasis, Geneva, Switzerland, July 8-12, 2007.

  • Susan R. Kahn, MD, MSc

      Affiliations

    • Department of Medicine, McGill University Faculty of Medicine, Montreal, QC, Canada
    • Corresponding Author InformationReprints: Susan R. Kahn, MD, MSc, Center for Clinical Epidemiology and Community Studies, Sir Mortimer B. Davis Jewish General Hospital, 3755 Cote Ste. Catherine, Rm. A-127, Montreal, Quebec, Canada H3T 1E2
    • ,
  • Robert Platt, PhD

      Affiliations

    • Department of Epidemiology and Biostatistics, McGill University Faculty of Medicine, Montreal, QC, Canada
    • Department of Pediatrics, McGill University Faculty of Medicine, Montreal, QC, Canada
    • ,
  • Helen McNamara, MD, MSc

      Affiliations

    • Department of Obstetrics and Gynecology, McGill University Faculty of Medicine, Montreal, QC, Canada
    • ,
  • Rima Rozen, MD, PhD

      Affiliations

    • Department of Pediatrics, McGill University Faculty of Medicine, Montreal, QC, Canada
    • Department of Human Genetics, McGill University Faculty of Medicine, Montreal, QC, Canada
    • ,
  • Moy Fong Chen, MD

      Affiliations

    • Department of Pathology, McGill University Faculty of Medicine, Montreal, QC, Canada
    • ,
  • Jacques Genest Jr, MD

      Affiliations

    • Department of Medicine, McGill University Faculty of Medicine, Montreal, QC, Canada
    • ,
  • Lise Goulet, MD, PhD

      Affiliations

    • Département de médecine sociale et préventive, Faculté de médecine, Université de Montréal, Montreal, QC, Canada
    • Groupe de recherche interdisciplinaire en santé, Université de Montréal, Montreal, QC, Canada
    • ,
  • John Lydon, PhD

      Affiliations

    • Department of Psychology, McGill University, Montreal, QC, Canada
    • ,
  • Louise Seguin, MD, MPH

      Affiliations

    • Département de médecine sociale et préventive, Faculté de médecine, Université de Montréal, Montreal, QC, Canada
    • ,
  • Clement Dassa, PhD

      Affiliations

    • Département de médecine sociale et préventive, Faculté de médecine, Université de Montréal, Montreal, QC, Canada
    • ,
  • André Masse, MD

      Affiliations

    • Département d'Obstetrique et gynécologie, Université de Montréal, Montreal, QC, Canada
    • ,
  • Guylaine Asselin, MD

      Affiliations

    • Département d'Obstetrique et gynécologie, Université de Montréal, Montreal, QC, Canada
    • ,
  • Alice Benjamin, MD

      Affiliations

    • Department of Obstetrics and Gynecology, McGill University Faculty of Medicine, Montreal, QC, Canada
    • ,
  • Louise Miner, MD

      Affiliations

    • Department of Obstetrics and Gynecology, McGill University Faculty of Medicine, Montreal, QC, Canada
    • ,
  • Antoinette Ghanem, RN, MSc

      Affiliations

    • Groupe de recherche interdisciplinaire en santé, Université de Montréal, Montreal, QC, Canada
    • ,
  • Michael S. Kramer, MD

      Affiliations

    • Department of Epidemiology and Biostatistics, McGill University Faculty of Medicine, Montreal, QC, Canada
    • Department of Pediatrics, McGill University Faculty of Medicine, Montreal, QC, Canada

Received 18 April 2008 ,Revised 25 July 2008 ,Accepted 22 September 2008.

References 

  1. Sibai B, Dekker G, Kupferminc M. Pre-eclampsia. Lancet. 2005;365:785–799
  2. National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy. Report of the national high blood pressure education program working group on high blood pressure in pregnancy. Am J Obstet Gynecol. 2000;183:S1–S22
  3. Kaunitz AM, Hughes JM, Grimes DA, et al. Causes of maternal mortality in the United States, 1979-1986. Am J Obstet Gynecol. 1990;163:460–465
  4. Duley L. Maternal mortality associated with hypertensive disorders of pregnancy in Africa, Asia, Latin America and the Caribbean. Br J Obstet Gynaecol. 1992;99:547–553
  5. Duckitt K, Harrington D. Risk factors for pre-eclampsia at antenatal booking: systematic review of controlled studies. BMJ. 2005;330:565
  6. Roberts JM, Cooper DW. Pathogenesis and genetics of pre-eclampsia. Lancet. 2001;357:53–56
  7. Rosendaal FR, Koster T, Vanderbroucke JP, Reitsma PH. High risk of thrombosis in patients homozygous for factor V Leiden. Blood. 1995;85:1504–1508
  8. Poort SR, Rosendaal FR, Reitsma PH, Bertina RM. A common genetic variation in the 3'-untranslated region of the prothrombin gene is associated with elevated prothrombin levels and an increase in venous thrombosis. Blood. 1996;88:3698–3703
  9. Frost P, Bloom HJ, Milos R, et al. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet. 1995;10:111–113
  10. Jacques PF, Bostom AG, Williams RR, et al. Relation between folate status, a common mutation in methylenetetrahydrofolate reductase, and plasma homocysteine concentrations. Circulation. 1996;93:7–9
  11. den Heijer M, Blom HJ, Gerrits WBJ, et al. Is hyperhomocysteinemia a risk factor for recurrent venous thrombosis?. Lancet. 1995;345:882–885
  12. Ridker PM, Hennekens CH, Selhub J, Miletich JP, Malinow MR, Stampfer MJ. Interrelation of hyperhomocyst(e)inemia, factor V Leiden, and risk of future venous thromboembolism. Circulation. 1997;95:1777–1782
  13. Eikelbloom JW, Lonn E, Genest J, Hankey G, Yusuf S. Homocyst(e)ine and cardiovascular disease: a critical review of epidemiologic evidence. Ann Intern Med. 1999;131:363–375
  14. Welch GN, Loscalzo J. Homocysteine and atherothrombosis. N Engl J Med. 1998;338:1042–1050
  15. Kupferminc MJ, Eldor A, Steinman N, et al. Increased frequency of genetic thrombophilia in women with complications of pregnancy. N Engl J Med. 1999;340:9–13
  16. Dizon-Townson DS, Helson LN, Easton K, Ward K. The factor V Leiden mutation may predispose women to severe preeclampsia. Am J Obstet Gynecol. 1996;175:902–905
  17. Grandone E, Margaglione M, Colaizzo D, et al. Factor V Leiden, C>T MTHFR polymorphism and genetic susceptibility to preeclampsia. Thromb Haemost. 1997;77:1052–1054
  18. Hubel CA. Oxidative stress in the pathogenesis of preeclampsia. Proc Soc Exp Biol Med. 1999;222:222–235
  19. Middeldorp S. Thrombophilia and pregnancy complications: cause or association?. J Thromb Haemost. 2007;5:276–282
  20. Kramer MS, Goulet L, Lydon J, et al. Socio-economic disparities in preterm birth: causal pathways and mechanisms. Paediatr Perinat Epidemiol. 2001;15(Suppl2):104–123
  21. Helewa ME, Burrows RF, Smith J, Williams K, Brain P, Rabkin SW. 1: definitions, evaluation and classification of hypertensive disorders in pregnancy. Can Med Assoc J. 1997;157:715–725
  22. Dekker GA, de Vries JIP, Doelitzsch PM, et al. Underlying disorders associated with severe early-onset preeclampsia. Am J Obstet Gynecol. 1995;173:1042–1048
  23. Kramer MS, Chen MF, Roy I, et al. Intra- and interobserver agreement and statistical clustering of placental histopathologic features relevant to preterm birth. Am J Obstet Gynecol. 2006;195:1674–1679
  24. Statistics Canada. Low income cut-offs. Catalogue 13-551-XIB, Dec. 1999. Ottawa, Canada.
  25. Breslow NE, Day NE. The design and analysis of cohort studies (Statistical methods in cancer research. Vol II). Lyon: IARC Scientific Publications; 1987;
  26. Dizon-Townson D, Miller C, Sibai B, et al. The relationship of the factor V Leiden mutation and pregnancy outcomes for mother and fetus. Obstet Gynecol. 2005;106:517–524
  27. Kocher O, Cirovic C, Malynn E, et al. Obstetric complications in patients with hereditary thrombophilia identified using the LCx microparticle enzyme immunoassay: a controlled study of 5,000 patients. Am J Clin Pathol. 2007;127:68–75
  28. March RE. Gene mapping by linkage and association analysis. Mol Biotechnol. 1999;13:113–122
  29. Robertson L, Wu O, Langhorne P, et al. Thrombophilia in pregnancy: a systematic review. Br J Haematol. 2006;132:171–196
  30. Morrison ER, Miedzybrodzka ZH, Campbell DM, et al. Prothrombotic genotypes are not associated with pre-eclampsia and gestational hypertension: results from a large population-based study and systematic review. Thromb Haemost. 2002;87:779–785
  31. Murphy RP, Donoghue C, Nallen RJ, et al. Prospective evaluation of the risk conferred by factor V Leiden and thermolabile methylenetetrahydrofolate reductase polymorphisms in pregnancy. Arterioscler Thromb Vasc Biol. 2000;20:266–270
  32. Lin J, August P. Genetic thrombophilias and preeclampsia: a meta-analysis. Obstet Gynecol. 2005;105:182–192
  33. Salafia CM, Pezzullo JC, López-Zeno JA, Simmens S, Minior VK, Vintzileos AM. Placental pathological features of preterm preeclampsia. Am J Obstet Gynecol. 1995;173:1097–1105
  34. Mousa HA, Alfirevic1 Z. Do placental lesions reflect thrombophilia state in women with adverse pregnancy outcome?. Hum Reprod. 2000;15:1830–1833
  35. Steegers-Theunissen RPM, Smith SC, Steegers EAP, Guilbert LJ, Baker PN. Folate affects apoptosis in human trophoblastic cells. BJOG. 2000;107:1513–1515
  36. Di Simone N, Riccardi P, Maggiano N, et al. Effect of folic acid on homocysteine-induced trophoblast apoptosis. Mol Hum Reprod. 2004;10:665–669
  37. Sanchez SE, Zhang C, Malinow MR, Ware-Jauregui S, Larrabure G, Williams MA. Plasma folate, vitamin B12, and homocyst(e)ine concentrations in preeclamptic and normotensive Peruvian women. Am J Epidemiol. 2001;153:474–480
  38. Rajkovic A, Mahomed K, Rozen R, Malinow MR, King IB, Williams MA. Methylenetetrahydrofolate reductase 677 C → T polymorphism, plasma folate, vitamin b12 concentrations, and risk of preeclampsia among black African women from Zimbabwe. Mol Genet Metab. 2000;69:33–39
  39. Chalmers B, Dzakpasu S, Heaman M, Kaczorowski J. The Canadian maternity experiences survey: an overview of findings. J Obstet Gynaecol Can. 2008;30:217–228
  40. Gerhardt A, Goecke TW, Beckmann MW, et al. the G20210A prothrombin-gene mutation and the plasminogen activator inhibitor (PAI-1) 5G/5G genotype are associated with early onset of severe preeclampsia. J Thromb Haemost. 2005;3:686–691
  41. Skjaerven R, Vatten LJ, Wilcox AJ, Ronning T, Irgens LM, Lie RT. Recurrence of pre-eclampsia across generations: exploring fetal and maternal genetic components in a population based cohort. BMJ. 2005;331:877
  42. Rodger MA, Paidas M, McLintock C, et al. Inherited thrombophilia and pregnancy complications revisited. Obstet Gynecol. 2008;112(2Pt1):320–324
  43. Kramer MS, Platt RW, Wen SW, et al. A new and improved population-based Canadian reference for birth weight for gestational age. Pediatrics. 2001;108:E35

 Cite this article as: Kahn SR, Platt R, McNamara H, et al. Inherited thrombophilia and preeclampsia within a multicenter cohort: the Montreal Preeclampsia Study. Am J Obstet Gynecol 2009;200:151.e1-151.e9.

 Supported by grants from the Canadian Institutes of Health Research (MOP36424) and the March of Dimes Birth Defects Foundation (PERI grant #20-FY04-38). Dr Kahn is a career clinical investigator (chercheur-boursier clinicien) of the Fonds de la recherche en santé du Québec. Dr Platt is a career investigator (chercheur-boursier) of the Fonds de la recherche en santé du Québec. Dr Kramer is a Senior Investigator of the Canadian Institutes of Health Research.

PII: S0002-9378(08)01082-X

doi: 10.1016/j.ajog.2008.09.023

American Journal of Obstetrics & Gynecology
Volume 200, Issue 2 , Pages 151.e1-151.e9 , February 2009

Article Tools

* Image Usage & Resolution