Mapping the theories of preeclampsia: The role of homocysteine

OBJECTIVE: We conducted a systematic review to examine the hypothesized mechanism through which homocysteine could lead to preedampsia. 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 hyperhomocysteinernia to preedampsia. TABULATION, INTEGRATION, AND RESULTS: Overall, there were higher serum homocysteine concentrations among pregnant women with preedampsia 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 preedampsia. The mechanisms underlying hyperhomocysteinemia (folate and vitamin B,, deficiency and genetic polymorphisms) were not found to be plausible, but markers of oxidative stress and endothelial dysfunction were higher in hyperhomocystemiemia. CONCLUSION: Homocysteine concentrations are slightly inedampsia and are considerably increased once precclampsia is established. However, bemuse of a lack of consistency in data, dose-response relationship, and biologic plausibility, the observed association cannot be considered causal from the current literature. (C) 2005 by The American College of Obstetricians and Gynecologists.