HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mignini, L. E. Articles by Khan, K. S. Search for Related Content PubMed PubMed Citation Articles by Mignini, L. E. Articles by Khan, K. S. Related Collections Basic Science Hypertension and PIH Meta-analysis Medical complications of pregnancy Obstetric complications of pregnancy

Mapping the Theories of Preeclampsia: The Role of Homocysteine

Luciano E. Mignini, MD^*, Pallavi M. Latthe, MRCOG^*, Jose Villar, MD, Mark D. Kilby, MD, MRCOG^*, Guillermo Carroli, MD and Khalid S. Khan, MSc, MRCOG^*

From the *Division of Reproductive and Child Health, Birmingham Women's Hospital, University of Birmingham, Birmingham, United Kingdom; UNDP/UNFPA/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction, Department of Reproductive Health and Research, World Health Organization, Geneva, Switzerland; and Centro Rosarino de Estudios Perinatales (CREP), WHO Collaborative Center in Maternal and Child Health, Rosario 2000, Argentina.

Address reprint requests to: Luciano E. Mignini, Department of Obstetrics and Gynaecology, Birmingham Women's Health Care NHS Trust, B15 2TG, Birmingham, UK; e-mail: L.Mignini{at}bham.ac.uk.

OBJECTIVE: We conducted a systematic review to examine the hypothesized mechanism through which homocysteine could lead to preeclampsia.

DATA SOURCES: We searched MEDLINE, EMBASE, BIOSIS, SciSearch, and bibliographies of primary and review articles, and we contacted experts.

METHODS OF STUDY SELECTION: Of the 25 relevant primary articles, 8 studies measured total serum homocysteine concentrations before the clinical onset of preeclampsia (1,876 women), whereas 17 measured it afterward (1,773 women). Meta-analytic techniques were used to examine consistency, strength, temporality, dose-response, and plausibility of the disease mechanisms implicating folate, vitamin B₆, vitamin B₁₂, genetic polymorphisms, oxidative stress, and endothelial dysfunction in the pathway linking hyperhomocysteinemia to preeclampsia.

TABULATION, INTEGRATION, AND RESULTS: Overall, there were higher serum homocysteine concentrations among pregnant women with preeclampsia than among those with uncomplicated pregnancies, but the results were heterogeneous (P = .12; I² = 38.8%). Among studies with temporality, the size of association was smaller than that among those without (weighted mean difference 0.68 µmol/L versus 3.36 µmol/L; P < .006). There was no dose-response relationship between homocysteine concentration and severity of preeclampsia. The mechanisms underlying hyperhomocysteinemia (folate and vitamin B₁₂ deficiency and genetic polymorphisms) were not found to be plausible, but markers of oxidative stress and endothelial dysfunction were higher in hyperhomocysteinemia.

CONCLUSION: Homocysteine concentrations are slightly increased in normotensive pregnancies that later develop preeclampsia and are considerably increased once preeclampsia is established. However, because of a lack of consistency in data, dose-response relationship, and biologic plausibility, the observed association cannot be considered causal from the current literature.

This article has been cited by other articles:

				L. Dodds, D. B. Fell, K. C. Dooley, B. A. Armson, A. C. Allen, B. A. Nassar, S. Perkins, and K.S. Joseph Effect of Homocysteine Concentration in Early Pregnancy on Gestational Hypertensive Disorders and Other Pregnancy Outcomes Clin. Chem., February 1, 2008; 54(2): 326 - 334. [Abstract] [Full Text] [PDF]

				M. Widmer, J. Villar, A. Benigni, A. Conde-Agudelo, S. A. Karumanchi, and M. Lindheimer Mapping the Theories of Preeclampsia and the Role of Angiogenic Factors: A Systematic Review Obstet. Gynecol., January 1, 2007; 109(1): 168 - 180. [Abstract] [Full Text] [PDF]

				L. M. Bodnar, G. Tang, R. B. Ness, G. Harger, and J. M. Roberts Periconceptional Multivitamin Use Reduces the Risk of Preeclampsia Am. J. Epidemiol., September 1, 2006; 164(5): 470 - 477. [Abstract] [Full Text] [PDF]

				H. Refsum, E. Nurk, A. D. Smith, P. M. Ueland, C. G. Gjesdal, I. Bjelland, A. Tverdal, G. S. Tell, O. Nygard, and S. E. Vollset The Hordaland Homocysteine Study: A Community-Based Study of Homocysteine, Its Determinants, and Associations with Disease J. Nutr., June 1, 2006; 136(6): 1731S - 1740S. [Abstract] [Full Text] [PDF]

				T. Tamura and M. F. Picciano Folate and human reproduction Am. J. Clinical Nutrition, May 1, 2006; 83(5): 993 - 1016. [Abstract] [Full Text] [PDF]

				B. M. Sibai Thrombophilia and Severe Preeclampsia: Time to Screen and Treat in Future Pregnancies? Hypertension, December 1, 2005; 46(6): 1252 - 1253. [Full Text] [PDF]