Download PDF
Am J Perinatol 2014; 31(02): 091-098
DOI: 10.1055/s-0033-1338171
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Vitamin C Supplementation in Pregnancy—Does It Decrease Rates of Preterm Birth? A Systematic Review

Paul Swaney
1   Department of Obstetrics and Gynecology, University of North Carolina, Chapel Hill, North Carolina
,
John Thorp
1   Department of Obstetrics and Gynecology, University of North Carolina, Chapel Hill, North Carolina
,
Ian Allen
2   Department of Radiation Oncology, University of North Carolina, Chapel Hill, North Carolina
› Author Affiliations
Further Information

Publication History

09 September 2012

10 January 2013

Publication Date:
18 March 2013 (online)

    Permissions and Reprints

Abstract

Objective To assess the evidence available on the use of vitamin C supplementation greater than recommended dietary intake to reduce preterm birth rates.

Study Design Systematic review of randomized controlled trials using vitamin C alone or with one other supplement other than iron. Trials must report preterm birth rates but can have other primary outcomes. Preterm birth is defined as birth at less than 37 weeks' gestational age for this review. Review focused on studies with populations representative of Organization for Economic Co-operation and Development countries.

Results Inadequate level of evidence on the use of vitamin C alone to prevent preterm birth rates in low-risk populations based on one study. Three studies provided convincing evidence of no benefit in low-risk groups of use of vitamins C and E combined. Three studies provided adequate evidence of no benefit in high-risk groups of use of vitamins C and E combined.

Conclusion The available evidence supports no benefit gained from using vitamin C to prevent preterm birth. Evidence does not support limiting use of vitamin C supplementation for other indications.

Keywords

vitamin C - ascorbic acid - preterm birth - prevention
 

  • References

  • 1 Mathews TJ, MacDorman MF. Infant mortality statistics from the 2005 period linked birth/infant death data set. Natl Vital Stat Rep 2008; 57: 1-32
    PubMedGoogle Scholar
  • 2 Swamy GK, Ostbye T, Skjaerven R. Association of preterm birth with long-term survival, reproduction, and next-generation preterm birth. JAMA 2008; 299: 1429-1436
    CrossrefPubMedGoogle Scholar
  • 3 Kochanek KD, Kirmeyer SE, Martin JA, Strobino DM, Guyer B. Annual summary of vital statistics: 2009. Pediatrics 2012; 129: 338-348
    CrossrefPubMedGoogle Scholar
  • 4 Beck S, Wojdyla D, Say L , et al. The worldwide incidence of preterm birth: a systematic review of maternal mortality and morbidity. Bull World Health Organ 2010; 88: 31-38
    Google Scholar
  • 5 Lykke JA, Paidas MJ, Langhoff-Roos J. Recurring complications in second pregnancy. Obstet Gynecol 2009; 113: 1217-1224
    CrossrefPubMedGoogle Scholar
  • 6 Edlow AG, Srinivas SK, Elovitz MA. Second-trimester loss and subsequent pregnancy outcomes: what is the real risk?. Am J Obstet Gynecol 2007; 197: 1-581
    CrossrefPubMedGoogle Scholar
  • 7 Goldenberg RL, Mayberry SK, Copper RL, Dubard MB, Hauth JC. Pregnancy outcome following a second-trimester loss. Obstet Gynecol 1993; 81: 444-446
    PubMedGoogle Scholar
  • 8 Wikstrom AK, Stephansson O, Cnattingius S. Previous preeclampsia and risks of adverse outcomes in subsequent nonpreeclamptic pregnancies. Am J Obstet Gynecol 2011; 204: 1-148
    CrossrefPubMedGoogle Scholar
  • 9 Chang JJ, Muglia LJ, Macones GA. Association of early-onset pre-eclampsia in first pregnancy with normotensive second pregnancy outcomes: a population-based study. BJOG 2010; 117: 946-953
    CrossrefPubMedGoogle Scholar
  • 10 Kyrklund-Blomberg NB, Cnattingius S. Preterm birth and maternal smoking: risks related to gestational age and onset of delivery. Am J Obstet Gynecol 1998; 179: 1051-1055
    CrossrefPubMedGoogle Scholar
  • 11 Sibai BM, Caritis SN, Hauth JC , et al. Preterm delivery in women with pregestational diabetes mellitus or chronic hypertension relative to women with uncomplicated pregnancies. The National institute of Child health and Human Development Maternal- Fetal Medicine Units Network. Am J Obstet Gynecol 2000; 183: 1520-1524
    CrossrefPubMedGoogle Scholar
  • 12 Slattery MM, Morrison JJ. Preterm delivery. Lancet 2002; 360: 1489-1497
    CrossrefPubMedGoogle Scholar
  • 13 Woods Jr JR, Plessinger MA, Miller RK. Vitamins C and E: missing links in preventing preterm premature rupture of membranes?. Am J Obstet Gynecol 2001; 185: 5-10
    CrossrefPubMedGoogle Scholar
  • 14 Myatt L, Cui X. Oxidative stress in the placenta. Histochem Cell Biol 2004; 122: 369-382
    CrossrefPubMedGoogle Scholar
  • 15 Davidge ST. Oxidative stress and altered endothelial cell function in preeclampsia. Semin Reprod Endocrinol 1998; 16: 65-73
    Article in Thieme ConnectPubMedGoogle Scholar
  • 16 Roberts JM, Hubel CA. Is oxidative stress the link in the two-stage model of pre-eclampsia?. Lancet 1999; 354: 788-789
    CrossrefPubMedGoogle Scholar
  • 17 Otten JJ, Hellwig JP, Meyers LD , eds. Dietary reference intakes: the essential guide to nutrient requirements. In: The National Academies Press; 2006:202–210. Available at: http://www.nap.edu/openbook.php?record_id=11537 . Accessibility verified February 3, 2012.
    PubMedGoogle Scholar
  • 18 Armitage P, Berry G. Statistical Methods in Medical Research. 3rd ed. Blackwell, Oxford, UK; , 1994
    Google Scholar
  • 19 U.S. Preventive Services Task Force Procedure Manual. AHRQ publication no. 08–05118-EF. Updated 2011. Available at: http://www.uspreventiveservicestaskforce.org/uspstf08/methods/procmanual.htm . Accessibility verified April 15, 2012.
    PubMedGoogle Scholar
  • 20 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
    PubMedGoogle Scholar
  • 21 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: 1-239
    CrossrefPubMedGoogle Scholar
  • 22 Roberts JM, Myatt L, Spong CY , et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Vitamins C and E to prevent complications of pregnancy-associated hypertension. N Engl J Med 2010; 362: 1282-1291
    CrossrefPubMedGoogle Scholar
  • 23 Rumbold AR, Crowther CA, Haslam RR, Dekker GA, Robinson JS. ACTS Study Group. Vitamins C and E and the risks of preeclampsia and perinatal complications. N Engl J Med 2006; 354: 1796-1806
    CrossrefPubMedGoogle Scholar
  • 24 McCance DR, Holmes VA, Maresh MJ , et al; Diabetes and Pre-eclampsia Intervention Trial (DAPIT) Study Group. Vitamins C and E for prevention of pre-eclampsia in women with type 1 diabetes (DAPIT): a randomised placebo-controlled trial. Lancet 2010; 376: 259-266
    CrossrefPubMedGoogle Scholar
  • 25 Poston L, Briley AL, Seed PT, Kelly FJ, Shennan AH. Vitamins in Pre-eclampsia (VIP) Trial Consortium. Vitamin C and vitamin E in pregnant women at risk for pre-eclampsia (VIP trial): randomised placebo-controlled trial. Lancet 2006; 367: 1145-1154
    Google Scholar
  • 26 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
    Google Scholar
  • 27 Chappell LC, Seed PT, Briley AL , et al. Effect of antioxidants on the occurrence of pre-eclampsia in women at increased risk: a randomised trial. Lancet 1999; 354: 810-816
    Google Scholar
  • 28 Steyn PS, Odendaal HJ, Schoeman J, Stander C, Fanie N, Grové D. A randomised, double-blind placebo-controlled trial of ascorbic acid supplementation for the prevention of preterm labour. J Obstet Gynaecol 2003; 23: 150-155
    CrossrefPubMedGoogle Scholar
  • 29 Spinnato II JA, Freire S, Pinto e Silva JL , et al. Antioxidant supplementation and premature rupture of the membranes: a planned secondary analysis. Am J Obstet Gynecol 2008; 199: 1-433
    CrossrefPubMedGoogle Scholar
  • 30 Villar J, Purwar M, Merialdi M , et al; WHO Vitamin C and Vitamin E trial group. World Health Organisation multicentre randomised 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
    CrossrefPubMedGoogle Scholar
  • 31 Luke B. The evidence linking maternal nutrition and prematurity. J Perinat Med 2005; 33: 500-505
    PubMedGoogle Scholar