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Pregnancy is a high-risk event in women with essential thrombocythemia (ET). This observational study evaluated pregnancy outcome in ET patients focusing on the potential impact of aspirin (ASA) or interferon alpha (IFN) treatment during pregnancy. We retrospectively analyzed 122 pregnancies in 92 women consecutively observed in the last 10 years in 17 centers of the Italian thrombocythemia registry (RIT). The live birth rate was 75.4% (92/122 pregnancies). The risk of spontaneous abortion was 2.5-fold higher than in the control population (P< 0.01). ASA did not affect the live birth rate (71/93, 76.3% vs. 21/29, 72.4%,P= 0.67). However, IFN treatment during pregnancy was associated with a better outcome than was management without IFN (live births 19/20, 95% vs. 73/102, 71.6%,P= 0.025), and this finding was supported by multivariate analysis (OR: 0.10; 95% CI: 0.013-0.846,P= 0.034). The JAK2 V617F mutation was associated with a poorer outcome (fetal losses JAK2 V617F positive 9/25, 36% vs. wild type 2/24, 8.3%,P= 0.037), and this association was still significant after multivariate analysis (OR: 6.19; 95% CI: 1.17-32.61;P= 0.038). No outcome concordance between first and second pregnancies was found (P= 0.30). Maternal complications occurred in 8% of cases. In this retrospective study, in consecutively observed pregnant ET patients, IFN treatment was associated with a higher live birth rate, while ASA treatment was not. In addition, the JAK2 V617F mutation was confirmed to be an adverse prognostic factor. Am. J. Hematol. 84:636-640, 2009. © 2009 Wiley-Liss, Inc.