American Journal of Obstetrics & Gynecology
Volume 202, Issue 3 , Pages 239.e1-239.e10 , March 2010

An international trial of antioxidants in the prevention of preeclampsia (INTAPP)

Presented orally at the 30th Annual Meeting of the Society for Maternal-Fetal Medicine, Chicago, IL, Feb. 1-6, 2010.

  • Hairong Xu, MD, MSc

      Affiliations

    • Department of Obstetrics and Gynecology, Hôpital Ste-Justine, Université de Montréal, Montreal, QC, Canada
    • ,
  • Ricardo Perez-Cuevas, MD, PhD

      Affiliations

    • Instituto Mexicano del Seguro Sosial, Mexico City, Mexico
    • ,
  • Xu Xiong, MD, PhD

      Affiliations

    • Tulane University, New Orleans, LA
    • ,
  • Hortensia Reyes, MD, PhD

      Affiliations

    • National Institute of Public Health, Cuernavaca, Mexico
    • ,
  • Chantal Roy, MSc

      Affiliations

    • Department of Obstetrics and Gynecology, Hôpital Ste-Justine, Université de Montréal, Montreal, QC, Canada
    • ,
  • Pierre Julien, PhD

      Affiliations

    • Centre de Recherche du CHUQ, Quebec, QC, Canada
    • ,
  • Graeme Smith, MD, PhD

      Affiliations

    • Kingston General Hospital, Kingston, ON, Canada
    • ,
  • Peter von Dadelszen, MBChB, DPhil

      Affiliations

    • Children's and Women's Health Centre of BC, Vancouver, BC, Canada
    • ,
  • Line Leduc, MD

      Affiliations

    • Department of Obstetrics and Gynecology, Hôpital Ste-Justine, Université de Montréal, Montreal, QC, Canada
    • ,
  • François Audibert, MD, PhD

      Affiliations

    • Department of Obstetrics and Gynecology, Hôpital Ste-Justine, Université de Montréal, Montreal, QC, Canada
    • ,
  • Jean-Marie Moutquin, MD, MSc

      Affiliations

    • CHUS/Hôpital Fleurimont, Sherbrooke, QC, Canada
    • ,
  • Bruno Piedboeuf, MD

      Affiliations

    • Centre de Recherche du CHUQ, Quebec, QC, Canada
    • ,
  • Bryna Shatenstein, PhD

      Affiliations

    • Institut Universitaire de Gériatrie, Montreal, QC, Canada
    • ,
  • Socorro Parra-Cabrera, PhD

      Affiliations

    • National Institute of Public Health, Cuernavaca, Mexico
    • ,
  • Pierre Choquette, MD

      Affiliations

    • Cité de la santé, Laval, QC, Canada
    • ,
  • Stephanie Winsor, MD

      Affiliations

    • McMaster Medical Centre, Hamilton, ON, Canada
    • ,
  • Stephen Wood, MD

      Affiliations

    • Foothills Hospital, Calgary, AB, Canada
    • ,
  • Alice Benjamin, MD

      Affiliations

    • Royal-Victoria Hospital, Montreal, QC, Canada
    • ,
  • Mark Walker, MD, MSc

      Affiliations

    • Ottawa Hospital, Ottawa, ON, Canada
    • ,
  • Michael Helewa, MD

      Affiliations

    • St-Boniface General Hospital, Winnipeg, MB, Canada
    • ,
  • Johanne Dubé, MD

      Affiliations

    • CHUM, Hôpital St-Luc, Montreal, QC, Canada
    • ,
  • Georges Tawagi, MD

      Affiliations

    • Ottawa Hospital, Ottawa, ON, Canada
    • ,
  • Gareth Seaward, MD

      Affiliations

    • Mount Sinaï Hospital, Toronto, ON, Canada
    • ,
  • Arne Ohlsson, MD, MSc

      Affiliations

    • Mount Sinaï Hospital, Toronto, ON, Canada
    • ,
  • Laura A. Magee, MD, MSc

      Affiliations

    • Children's and Women's Health Centre of BC, Vancouver, BC, Canada
    • ,
  • Femi Olatunbosun, MD

      Affiliations

    • Royal University Hospital, Saskatoon, SK, Canada
    • ,
  • Robert Gratton, MD, MSc

      Affiliations

    • St Joseph's Health Centre, London, ON, Canada
    • ,
  • Roberta Shear, MD

      Affiliations

    • Jewish General Hospital, Montreal, QC, Canada
    • ,
  • Nestor Demianczuk, MD

      Affiliations

    • Royal-Alexandra Hospital, Edmonton, AB, Canada
    • ,
  • Jean-Paul Collet, MD, PhD

      Affiliations

    • Children's and Women's Health Centre of BC, Vancouver, BC, Canada
    • ,
  • Shuqin Wei, MD, PhD

      Affiliations

    • Department of Obstetrics and Gynecology, Hôpital Ste-Justine, Université de Montréal, Montreal, QC, Canada
    • ,
  • William D. Fraser, MD, MSc; and

      Affiliations

    • Department of Obstetrics and Gynecology, Hôpital Ste-Justine, Université de Montréal, Montreal, QC, Canada
    • Corresponding Author InformationReprints: William D. Fraser, MD, MSc, Department of Obstetrics and Gynecology, Université de Montréal, 3175 Chemin de la Côte Sainte-Catherine, Montreal (Quebec) Canada H3T 1C5
    • ,
  • INTAPP study group

Received 21 November 2009 ,Revised 13 January 2010 ,Accepted 19 January 2010.

References 

  1. Helewa ME, Burrows RF, Smith J, Williams K, Brain P, Rabkin SW. Report of the Canadian Hypertension Society consensus conference, 1: definitions, evaluation and classification of hypertensive disorders in pregnancy. CMAJ. 1997;157:715–725
  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(Suppl):1–22
  3. American College of Obstetricians and Gynecologists (ACOG). Hypertension in pregnancy: ACOG technical bulletin no. 219. Washington, DC: ACOG; 1996;
  4. Duley L. The global impact of pre-eclampsia and eclampsia. Semin Perinatol. 2009;33:130–137
  5. Khan KS, Wojdyla D, Say L, Gulmezoglu AM, Van Look PF. WHO analysis of causes of maternal death: a systematic review. Lancet. 2006;367:1066–1074
  6. Xiong X, Mayes D, Demianczuk N, et al. Impact of pregnancy-induced hypertension on fetal growth. Am J Obstet Gynecol. 1999;180:207–213
  7. Xiong X, Demianczuk NN, Buekens P, Saunders LD. Association of preeclampsia with high birth weight for age. Am J Obstet Gynecol. 2000;183:148–155
  8. Xiong X, Demianczuk NN, Saunders LD, Wang FL, Fraser WD. Impact of preeclampsia and gestational hypertension on birth weight by gestational age. Am J Epidemiol. 2002;155:203–209
  9. Xiong X, Saunders LD, Wang FL, Davidge ST, Buekens P. Preeclampsia and cerebral palsy in low-birth-weight and preterm infants: implications for the current ”ischemic model” of preeclampsia. Hypertens Pregnancy. 2001;20:1–13
  10. Hnat MD, Sibai BM, Caritis S, et al. Perinatal outcome in women with recurrent preeclampsia compared with women who develop preeclampsia as nulliparas. Am J Obstet Gynecol. 2002;186:422–426
  11. Casanueva E, Viteri FE. Iron and oxidative stress in pregnancy. J Nutr. 2003;133:1700S–1708S
  12. Hubel CA. Dyslipidemia, iron, and oxidative stress in preeclampsia: assessment of maternal and feto-placental interactions. Semin Reprod Endocrinol. 1998;16:75–92
  13. Raijmakers MT, Dechend R, Poston L. Oxidative stress and preeclampsia: rationale for antioxidant clinical trials. Hypertension. 2004;44:374–380
  14. Zhou JF, Wang XY, Shangguan XJ, et al. Increased oxidative stress in women with pregnancy-induced hypertension. Biomed Environ Sci. 2005;18:419–426
  15. Orhan H, Onderoglu L, Yucel A, Sahin G. Circulating biomarkers of oxidative stress in complicated pregnancies. Arch Gynecol Obstet. 2003;267:189–195
  16. Hubel CA, McLaughlin MK, Evans RW, Hauth BA, Sims CJ, Roberts JM. Fasting serum triglycerides, free fatty acids, and malondialdehyde are increased in preeclampsia, are positively correlated, and decrease within 48 hours post partum. Am J Obstet Gynecol. 1996;174:975–982
  17. Barden A, Beilin LJ, Ritchie J, Croft KD, Walters BN, Michael CA. Plasma and urinary 8-iso-prostane as an indicator of lipid peroxidation in pre-eclampsia and normal pregnancy. Clin Sci (Colch). 1996;91:711–718
  18. Roggensack AM, Zhang Y, Davidge ST. Evidence for peroxynitrite formation in the vasculature of women with preeclampsia. Hypertension. 1999;33:83–89
  19. Staff AC, Halvorsen B, Ranheim T, Henriksen T. Elevated level of free 8-iso-prostaglandin F2alpha in the decidua basalis of women with preeclampsia. Am J Obstet Gynecol. 1999;181:1211–1215
  20. Chappell LC, Seed PT, Briley AL, et al. Effect of antioxidants on the occurrence of pre-eclampsia in women at increased risk: a randomized trial. Lancet. 1999;354:810–816
  21. Beazley D, Ahokas R, Livingston J, Griggs M, Sibai BM. Vitamin C and E supplementation in women at high risk for preeclampsia: a double-blind, placebo-controlled trial. Am J Obstet Gynecol. 2005;192:520–521
  22. Poston L, Briley AL, Seed PT, Kelly FJ, Shennan AH. Vitamin C and vitamin E in pregnant women at risk for pre-eclampsia (VIP trial): randomized placebo-controlled trial. Lancet. 2006;367:1145–1154
  23. Rumbold AR, Crowther CA, Haslam RR, Dekker GA, Robinson JS. Vitamins C and E and the risks of preeclampsia and perinatal complications. N Engl J Med. 2006;354:1796–1806
  24. Spinnato JA, Freire S, Pinto ESJL, et al. Antioxidant therapy to prevent preeclampsia: a randomized controlled trial. Obstet Gynecol. 2007;110:1311–1318
  25. Villar J, Purwar M, Merialdi M, et al. World Health Organization multicenter randomized trial of supplementation with vitamins C and E among pregnant women at high risk for pre-eclampsia in populations of low nutritional status from developing countries. BJOG. 2009;116:780–788
  26. Magee LA, Helewa M, Moutquin JM, et al. SOGC guidelines; diagnosis, evaluation and management of the hypertensive disorders of pregnancy. J Obstet Gynaecol Can. 2008;30:1S–48S
  27. 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
  28. McDonald SD, Best C, Lam K. The recurrence risk of severe de novo pre-eclampsia in singleton pregnancies: a population-based cohort. BJOG. 2009;116:1578–1584
  29. Hauth JC, Ewell MG, Levine RJ, et al. Pregnancy outcomes in healthy nulliparas who developed hypertension: calcium for preeclampsia prevention study group. Obstet Gynecol. 2000;95:24–28
  30. Rivas-Echeverria CA, Echeverria Y, Molina L, Novoa D. Synergic use of aspirin, fish oil, and vitamins C and E for the prevention of preeclampsia. Hypertens Pregnancy. 2000;19:30
  31. Steyn PS, Odendaal HJ, Schoeman J, Stander C, Fanie N, Grove D. A randomized, double-blind placebo-controlled trial of ascorbic acid supplementation for the prevention of preterm labor. J Obstet Gynaecol. 2003;23:150–155
  32. Casanueva E, Ripoll C, Tolentino M, et al. Vitamin C supplementation to prevent premature rupture of the chorioamniotic membranes: a randomized trial. Am J Clin Nutr. 2005;81:859–863
  33. Roberts LJ, Oates JA, Linton MF, et al. The relationship between dose of vitamin E and suppression of oxidative stress in humans. Free Radic Biol Med. 2007;43:1388–1393
  34. Banerjee S, Chambers AE, Campbell S. Is vitamin E a safe prophylaxis for preeclampsia?. Am J Obstet Gynecol. 2006;194:1228–1233
  35. Baker H, Handelman GJ, Short S, et al. Comparison of plasma alpha and gamma tocopherol levels following chronic oral administration of either all-rac-alpha-tocopheryl acetate or RRR-alpha-tocopheryl acetate in normal adult male subjects. Am J Clin Nutr. 1986;43:382–387
  36. Eichhorn JC, Lee R, Dunster C, Basu S, Kelly FJ. Alpha- and gamma-tocopherol plasma and urinary biokinetics following alpha-tocopherol supplementation. Ann N Y Acad Sci. 2004;1031:339–340
  37. Morinobu T, Yoshikawa S, Hamamura K, Tamai H. Measurement of vitamin E metabolites by high-performance liquid chromatography during high-dose administration of alpha-tocopherol. Eur J Clin Nutr. 2003;57:410–414
  38. Jiang Q, Christen S, Shigenaga MK, Ames BN. Gamma-tocopherol, the major form of vitamin E in the US diet, deserves more attention. Am J Clin Nutr. 2001;74:714–722
  39. Gagné A, Xu H, Fraser WD. Plasma levels of vitamin E and coenzyme Q10 in women at high or low risk to develop preeclampsia: the INTAPP study. Can J Cardiol. 2008;24:52E
  40. Witztum JL. To E or not to E–how do we tell?. Circulation. 1998;98:2785–2787
  41. Meagher EA, Barry OP, Lawson JA, Rokach J, FitzGerald GA. Effects of vitamin E on lipid peroxidation in healthy persons. JAMA. 2001;285:1178–1182

 Sponsored by the Canadian Institutes of Health Research.

 The racing flag logo above indicates that this article was rushed to press for the benefit of the scientific community.

 Cite this article as: Xu H, Perez-Cuevas R, Xiong X, et al. An international trial of antioxidants in the prevention of preeclampsia (INTAPP). Am J Obstet Gynecol 2010;202:239.e1-10.

PII: S0002-9378(10)00080-3

doi: 10.1016/j.ajog.2010.01.050

American Journal of Obstetrics & Gynecology
Volume 202, Issue 3 , Pages 239.e1-239.e10 , March 2010

Article Tools

* Image Usage & Resolution