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Results of this systematic literature review suggest that the overall incidence of CMs in children born of WWE is approximately threefold that of healthy women. The risk is elevated for all AED monotherapy and further elevated for AED polytherapy compared to women without epilepsy. The risk was significantly higher for children exposed to valproate monotherapy and to polytherapy of 2 or more drugs when the polytherapy combination included phenobarital, phenytoin, or valproate. Further research is needed to delineate the specific risk for each individual AED and to determine underlying mechanisms including genetic risk factors.

Disclosure: S.D.R., C.A.P., S.M.C., B.S., and G.R. are employees of United BioSource Corporation (UBC) performing contract work for Amgen. I.E.A. received financial compensation from UBC for statistical consulting and reviewing the manuscript. No potential conflicts of interest were reported by the planners, reviewers, or staff managers of this article. LEARNING OBJECTIVESAfter completing this course, the reader will be able to:1. Provide the current best estimates of hemoglobin response with erythropoiesis-stimulating proteins in anemia of MDS.2. Specify prognostic factors for response that are potentially useful.3. Describe the gaps in the existing evidence base regarding these agents in MDS.Access and take the CME test online and receive 1 AMA PRA Category 1 Credit ™ at CME.TheOncologist.com CME CME ABSTRACT Objective. The objective was to assess the efficacy and safety of erythropoiesis-stimulating proteins (ESPs) in anemia of myelodysplastic syndrome (MDS).Method. A systematic review and meta-analysis was conducted covering English-language studies published from 1980 to December 2005.Results. Fifty-nine studies qualified: five controlled trials (n ‫؍‬ 354), all epoetin versus control (EvC); 51 epoetin single-arm studies (n ‫؍‬ 1,650); and three darbepoetin single-arm studies (n ‫؍‬ 102). In the EvC studies, epoetin patients demonstrated a significant advantage over controls in terms of hemoglobin (Hb) response (odds ratio, 5.2; 95% confidence interval, 2.5-10.8). Hb response was 48.1% in single-arm darbepoetin studies, 32.1% in epoetin single-arm studies, and 27.3% in EvC studies. Major Hb response averaged 38.8% in darbepoetin studies, 24.5% in epoetin single-arm studies, and 11.4% in EvC studies. Stratified analyses suggest that lower baseline erythropoietin levels, longer treatment durations, and concurrent iron may be associated with greater Hb response to ESPs. None of the analyzable predictors of Hb response (gender, baseline Hb, ESP type, and ESP duration) were significant in meta-regression analyses. In the few studies with quality-of-life measures, ESP groups attained a pre-post change (Functional Assessment of Cancer Therapy -Fatigue) that exceeded minimum clinically important differences. Selected adverse event rates did not differ between the epoetin and darbepoetin groups.Conclusion. Published studies suggest that ESPs are efficacious in anemia of MDS. Hb response appears higher in darbepoetin patients than in epoetin patients, and safety appears comparable, but darbepoetin data are sparse, and there are as yet no direct comparison studies.