Folic acid supplementation in early second trimester and the risk of preeclampsia.

OBJECTIVE The objective of the study was to evaluate the association between folic acid supplementation in early second trimester and the risk of developing preeclampsia. STUDY DESIGN We carried out a prospective cohort study between October 2002-December 2005. We recruited women who had their prenatal care visit (12-20 weeks' gestation) at the Ottawa Hospital and Kingston General Hospital. All charts for participants with a diagnosis of preeclampsia were audited and blindly adjudicated by 4 study investigators to validate the diagnosis. RESULTS A total of 2951 pregnant women were included in the final analysis. Supplementation of multivitamins containing folic acid was associated with increased serum folate (on average 10.51 micromol/L), decreased plasma homocysteine (on average 0.39 micromol/L), and reduced risk of preeclampsia (adjusted odds ratio, 0.37; 95% confidence interval, 0.18-0.75). CONCLUSION Supplementation of multivitamins containing folic acid in the second trimester is associated with reduced risk of preeclampsia.

[1]  S. Neubauer,et al.  5-Methyltetrahydrofolate Rapidly Improves Endothelial Function and Decreases Superoxide Production in Human Vessels: Effects on Vascular Tetrahydrobiopterin Availability and Endothelial Nitric Oxide Synthase Coupling , 2006, Circulation.

[2]  L. Poston,et al.  Vitamin C and vitamin E in pregnant women at risk for pre-eclampsia (VIP trial): randomised placebo-controlled trial , 2006, The Lancet.

[3]  Plasma Homocysteine as a Risk Factor for Vascular Disease , 1998 .

[4]  R. Goldenberg,et al.  Second-trimester plasma homocysteine levels and pregnancy-induced hypertension, preeclampsia, and intrauterine growth restriction. , 2000, American journal of obstetrics and gynecology.

[5]  J. Manson,et al.  Folate and vitamin B6 from diet and supplements in relation to risk of coronary heart disease among women. , 1998, JAMA.

[6]  Caroline A Crowther,et al.  Vitamins C and E and the risks of preeclampsia and perinatal complications. , 2006, New England Journal of Medicine.

[7]  M. Dunbar,et al.  The 677 C‐T Methylenetetrahydrofolate Reductase Mutation Does Not Predict Increased Maternal Homocysteine During Pregnancy , 2003, Obstetrics and gynecology.

[8]  J. G. Donnelly,et al.  Genetic determinants of heritable venous thrombosis: genotyping methods for factor V(Leiden)A1691G, methylenetetrahydrofolate reductase C677T, prothrombin G20210A mutation, and algorithms for venous thrombosis investigations. , 1999, Clinical biochemistry.

[9]  Gynecologists ACOG PRACTICE BULLETIN , 2009 .

[10]  Graeme N. Smith,et al.  Changes in homocysteine levels during normal pregnancy. , 1999, American journal of obstetrics and gynecology.

[11]  James M. Roberts,et al.  Antioxidant therapy to prevent preeclampsia. , 2004, Seminars in nephrology.

[12]  R. Ness,et al.  Periconceptional multivitamin use reduces the risk of preeclampsia. , 2006, American journal of epidemiology.

[13]  J. Witteman,et al.  Plasma homocysteine as a risk factor for vascular disease. The European Concerted Action Project. , 1997, JAMA.

[14]  G. Prescott,et al.  Hypertensive diseases of pregnancy and risk of hypertension and stroke in later life: results from cohort study , 2003, BMJ : British Medical Journal.

[15]  M. Mamdani,et al.  Association between folic acid food fortification and hypertension or preeclampsia in pregnancy. , 2002, Archives of internal medicine.

[16]  H. Bauchner,et al.  Effects of maternal marijuana and cocaine use on fetal growth. , 1989, The New England journal of medicine.

[17]  C. Laskin,et al.  Folic acid and homocyst(e)ine metabolic defects and the risk of placental abruption, pre-eclampsia and spontaneous pregnancy loss: A systematic review. , 1999, Placenta.

[18]  A. Conde-Agudelo,et al.  Maternal-perinatal morbidity and mortality associated with adolescent pregnancy in Latin America: Cross-sectional study. , 2005, American journal of obstetrics and gynecology.

[19]  I. Johnson,et al.  Plasma from pre‐eclamptic women and functional change in myometrial resistance arteries , 1998, British journal of obstetrics and gynaecology.

[20]  M. Bots,et al.  Effect of Folic Acid and Betaine Supplementation on Flow-Mediated Dilation: A Randomized, Controlled Study in Healthy Volunteers , 2006, PLoS clinical trials.

[21]  J. Roberts,et al.  Clinical and biochemical evidence of endothelial cell dysfunction in the pregnancy syndrome preeclampsia. , 1991, American journal of hypertension.

[22]  L. Poston,et al.  Vitamin C and vitamin e in pregnant women at risk for pre-eclampsia (VIP trial) : Randomized placebo-controlled trial , 2006 .

[23]  R. Ness,et al.  Plasma homocysteine concentration is increased in preeclampsia and is associated with evidence of endothelial activation. , 1998, American journal of obstetrics and gynecology.

[24]  E. Ur,et al.  Folic acid improves endothelial dysfunction in type 2 diabetes - an effect independent of homocysteine-lowering , 2006, Vascular medicine.