Document Detail

Mapping the theories of preeclampsia: the role of homocysteine.
MedLine Citation:
PMID:  15684173     Owner:  NLM     Status:  MEDLINE    
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 B(6), vitamin B(12), 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; I(2) = 38.8%). Among studies with temporality, the size of association was smaller than that among those without (weighted mean difference 0.68 mumol/L versus 3.36 mumol/L; P < .006). There was no dose-response relationship between homocysteine concentration and severity of preeclampsia. The mechanisms underlying hyperhomocysteinemia (folate and vitamin B(12) 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.
Luciano E Mignini; Pallavi M Latthe; Jose Villar; Mark D Kilby; Guillermo Carroli; Khalid S Khan
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Publication Detail:
Type:  Comparative Study; Journal Article; Meta-Analysis; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Obstetrics and gynecology     Volume:  105     ISSN:  0029-7844     ISO Abbreviation:  Obstet Gynecol     Publication Date:  2005 Feb 
Date Detail:
Created Date:  2005-02-01     Completed Date:  2005-03-10     Revised Date:  2009-10-26    
Medline Journal Info:
Nlm Unique ID:  0401101     Medline TA:  Obstet Gynecol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  411-25     Citation Subset:  AIM; IM    
Division of Reproductive and Child Health, Department of Obstetrics and Gynaecology, Birmingham Women's Hospital, University of Birmingham, Birmingham B15 2TG, United Kingdom.
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MeSH Terms
Age Factors
Biological Markers / blood
Folic Acid / blood
Gestational Age
Homocysteine / blood*,  metabolism
Hyperhomocysteinemia / blood,  complications,  physiopathology*
Maternal Age
Pre-Eclampsia / blood*,  prevention & control*
Predictive Value of Tests
Primary Prevention
Randomized Controlled Trials as Topic
Risk Assessment
Sensitivity and Specificity
Survival Rate
Vitamin B 12 / blood
Reg. No./Substance:
0/Biological Markers; 454-28-4/Homocysteine; 59-30-3/Folic Acid; 68-19-9/Vitamin B 12

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