Abstract
Placental abruption is due to the rupture of the uterine spiral artery. The placenta
separates totally or partially from the uterine wall during pregnancy. This serious
syndrome has a great risk for the mother (shock and disseminated intravascular coagulation)
and her child (mortality or morbidity).
To the known risk factors like hypertension, the use of cocaine and smoking, homocysteine
is recognized as an independent risk factor for vascular disease and endothelial dysfunction.
In contrast to normal pregnancy where the spiral artery endothelium is replaced by
trophoblast, the endothelium persists in case of placental abruption.
In 165 women with placental vasculopathy and 139 matched controls hyperhomocysteinemia
resulted in an odds ratio of 4.7 (95% CI: 1.6–14.0). The C677T mutation gave a risk
of 2.5 (95% CI: 1.0–6.0). Even up to 2 or 3 years post-partum evidence could be found
of endothelial dysfunction.
The combination of hyperhomocysteinemia and thrombotic factors like APC resistance,
Protein-C, Protein-S, antithrombin and factor V Leiden increases the risk of placental
abruption 3–7 times.
The common denominator of the effect of homocysteine on bloodvessels could be sited
in the process of proliferation of cells that need proper methyl groups for proper
function (DNA synthesis and expression). These methyl groups are delivered by d-adenosylmethionine formed from methionine after remethylation of homocysteine.
The coagulation factors and plasma homocysteine values can be modulated by vitamins,
folic acid and folates in particular. To prove the clinical value of folate supplementation
placebo-randomized trials are urgently needed: for placebo to be started after the
period of neural tube closure.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to European Journal of Obstetrics and Gynecology and Reproductive BiologyAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Incidence of placental abruption in relation to cigarette smoking and hypertensive disorders during pregnancy: a meta-analysis of observational studies.Obstet. Gynecol. 1999; 93: 622-628
- Common methylenetetrahydrofolate reductase gene mutation leads to hyperhomocysteinemia but not to vascular disease: the result of a meta-analysis.Circulation. 1998; 98: 2520-2526
- The physiological response of the vessels of the placental bed to normal pregnancy.J. Pathol. Bact. 1967; 93: 569-572
Clarke R, Daly L, Robinson K, Naughten E, Cahalane S, Fowler B, Graham I, Hyperhomocysteinemia: an independent risk factor for vascular disease, N Engl J Med 1991;324:1149-55.
- Lowering blood homocysteine with folic acid based supplements: meta-analysis of randomised trials.Br. Med. J. 1998; 316: 894-898
- Hyperhomocysteinemia and Protein-S in complicated pregnancies.Brit. J. Obstet. Gynaecol. 1997; 104: 1248-1254
- Placental bed biopsies in placental abruption.Brit. J. Obstet. Gynaecol. 1992; 99: 651-654
- Pathophysiology of antiphospholipid antibodies: absence of prostaglandin-mediated effects on cultured endothelium.Am. J. Obstet. Gynecol. 1990; 162: 53-59
- Abruptio placentae: a “classic” dedicated to Elizabeth Ramsey.Eur. J. Obstet. Gynecol. Reprod. Biol. 1997; 75: 63-71
- Open or closed? A world of difference: a history of homocysteine research.Nutr. Rev. 1998; 56: 236-244
- Methionine metabolism in mammals.J. Nutr. Biochem. 1990; 1: 228-237
Frosst P, Blom HJ, Milos R, Goyette P, Sheppard CA, Matthews RG, Boers GHJ, Den Heijer M, Kluijtmans LAJ, Van den Heuvel LP, Rozen R. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nature Genet 1995;111–3.
- Isolation and purification of microvascular endothelium from human decidual tissue in the late phase of pregnancy.Am. J. Obstet. Gynecol. 1991; 165: 191-196
- In vitro human decidual endothelial cell thromboxane secretion in preeclampsia is not abnormal.Hypertens. Pregn. 1999; 18: 219-227
- Hperhomocysteinemia: a risk factor for placental abruption or infarction.Eur. J. Obstet. Gynecol. Reprod. Biol. 1996; 66: 23-29
- Human methylenetetrahydrofolate reductase: isolation of cDNA, mapping and mutation identification.Nature Genet. 1994; 7: 195-204
- Homocysteine and vascular disease.Lancet. 1999; 354: 407-413
- The common “thermolabile” variant of methylenetetrahydrofolate reductase is a major determinant of mild hyperhomocysteinaemia.Q. J. Med. 1996; 9: 577
Hibbard BM, Hibbard ED. Aetiologic factors in abruptio placentae. Br Med J 1963;2:1431–6.
- The role of folic acid in pregnancy, with particular reference to anaemia, abruption and abortion.J. Obstet. Gynaecol. Br. Commonwlth. 1964; 71: 529-542
Homocysteine lowering trialist’s collaboration. Lowering blood homocysteine with folic acid based supplements: meta-analysis of randomised trials, Br Med J 1998;316:894–898.
- Perinatal mortalty and late sequelae in children born after abruptio placentae.Eur. J. Obstet. Gynecol. Reprod. Biol. 1979; 9: 45-49
- Relation between folate status, a common mutation in the methylenetetrahydrofolate reductase, and plasma homocysteine concentrations.Circulation. 1996; 93: 7-9
- Congenital heart defects and derangement of homocysteine metabolism.J. Pediatrics. 1999; 135: 773-774
- Etiologic determinants of abruptio placentae.Obstet. Gynecol. 1997; 89: 221-226
- Increased frequency of genetic thrombophilia in women with complications of pregnancy.N. Engl. J. Med. 1999; 340: 9-13
- Methylenetetrahydrofolate reductase polymorphism dietary interactions and risk of colorectal cancer.Cancer Res. 1997; 57: 1102
- The effects of folic acid supplementation on plasma total homocysteine are modulated by multivitamin use and methylenetetrahydrofolate reductase genotypes.Arterioscler. Thromb. Vasc. Biol. 1997; 17: 1157-1162
- Vascular pathology of homocysteinemia: implications for the pathogenesis of arteriosclerosis.Am. J. Pathol. 1969; 56: 111-128
MRC Vitamin Study Research Group. Prevention of neural tube defects: results of the Medical Research Council vitamin study. Lancet 1991;338:131–7.
- Hyperhomocysteinemia — a risk factor for abruptio placentae.J. Inher. Metab. Dis. 1997; 20: 359-362
- Increased fetal loss in women with heritable thrombophilia.Lancet. 1996; 348: 913-916
- Coagulation eclampsia: their frequency and pathogenesis.Am. J. Obstet. Gynecol. 1976; 124: 855-864
- Review article: trophoblast invasion and the establishment of haemochorial placentation in man and laboratory animals.Placenta. 1981; 2: 71-92
- Second-trimester pregnancy loss is associated with activated protein C resistance.Br. J. Haematol. 1996; 92: 489-490
- Folic acid and homocyt(e)ine metabolic defects and the risk of placental abruption, pre-eclampsia and spontaneous pregnancy loss: a systematic review.Placenta. 1999; 20: 519-529
- Placental abruption: maternal risk factors and associated fetal conditions.Acta Obstet. Gynecol. Scand. 1993; 72: 633-639
- Placental thrombi and other vascular lesions, classification, morphology, and clinical correlations.Pathol. Res. Pract. 1993; 189: 2-17
- Folate and vitamin B6 from diet and supplements in relation to risk of coronary heart disease among women.JAMA. 1998; 279: 359-364
- Preeclampsia: an endothelial disorder.Am. J. Obstet. Gynecol. 1989; 161: 1200-1204
- The risk of abortion and stillbirth in antithrombin-protein C, and protein S, deficient women.Thromb. Haemost. 1996; 75: 387-388
- Detection of heterozygotes for homocystinuria.Arch. Dis. Child. 1974; 49: 553-559
- Neural-tube defects and derangement of homocysteine metabolism.N. Engl. J. Med. 1991; 324: 199-200
- Hyperhomocysteinaemia and recurrent spontaneous abortion or abruptio placentae (letter).Lancet. 1992; 1: 1122-1123
- Maternal hyperhomocysteinemia: a risk factor for neural-tube defects.Metabolism. 1994; 43: 1475-1480
- Abnormalities of vascular function in hyperhomocystenaemia: relationship to atherothrombotic disease.Eur. J. Pediatr. 1998; 157: S107-S111
- Hyperhomocysteinemia is associated with impaired endothelium-dependent vasodilatation in humans.Circulation. 1997; 95: 1119-1121
- Promotion of vascular smooth muscle cell growth by homocysteine: a link to atherosclerosis.Proc. Natl. Acad. Sci. U.S.A. 1994; 91: 6369-6373
- Induction of cyclin A gene expression by homocysteine in vascular smooth muscle cells.J. Clin. Invest. 1996; 97: 146-153
Van Aken B, Inflammatory markers, vascular disease and homocysteine. Ph.D. Thesis, University of Amsterdam (NL) 1999.
- The effect of folic acid on the homocysteine metabolism on human umbilical vein endothelial cells (HUVEC’s).Eur. J. Clin. Invest. 1996; 26: 304-309
Van der Molen EF. Disturbed homocysteine metabolism, endothelial dysfunction and placental vasculopathy. Ph.D. Thesis, University of Nijmegen (NL) 2000.
Verhoef P, Meleady R, Daly LE, Graham IM, Robinson K, Boers GHJ, and the European COMAC group. Homocysteine, vitamin status and risk of vascular disease. Effects of gender and menopausal status. Eur Heart J 1999;20:1234–44.
- Effect of homcysteine-lowering treatment with folic acid plus vitamin B6 on progression of subclinical atherosclerosis: a randomised, placebo-controlled trial.Lancet. 2000; 355: 517-522
- Activation of endothelial cells by plasma from women with preeclampsia: differential effects on four endothelial cell types.J. Soc. Gynecol. Invest. 1998; 5: 31-37
- Nonsyndromic orofacial clefts association with maternal hyperhomocysteinemia.Teratology. 1999; 60: 253-257
Boers GHJ. Homocystinuria: Homozygosity versus heterozygosity. Ph.D. Thesis, University Nijmegen (NL) 1985.
Article info
Footnotes
☆Invited lecture for Third Symposium organized by the Wim Schellekens Foundation, “Thrombophilia and Reproduction”, Friday, 16 June 2000, Westeinde Hospital, The Hague (NL) (070200, 080200, 090200, 100200, 110200, 060600).
Identification
Copyright
© 2001 Elsevier Science Ireland Ltd. Published by Elsevier Inc. All rights reserved.
