Published Online
on November 22, 2004

A more recent version of this article appeared on January 1, 2005

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Submitted on July 27, 2004
Revised on August 20, 2004

Low-Molecular-Weight Heparin Lowers the Recurrence Rate of Preeclampsia and Restores the Physiological Vascular Changes in Angiotensin-Converting Enzyme DD Women

Giorgio Mello^*; Elena Parretti; Cinzia Fatini; Chiara Riviello; Francesca Gensini; Mauro Marchionni; Gian Franco Scarselli; Gian Franco Gensini; and Rosanna Abbate

From the Departments of Gynecology, Perinatology, and Human Reproduction (G.M., E.P., C.R., M.M., G.F.S.); Medical and Surgical Critical Care (C.F., G.F.G., R.A.), Section of Clinical Medicine and Cardiology; and Physiopathology (F.G.), Section of Medical Genetics, University of Florence, Florence, Italy.

^* To whom correspondence should be addressed. E-mail: mellog{at}unifi.it.

Abstract--Data from literature report that angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism affects the recurrence of preeclampsia and that low-molecular-weight heparin (LMWH) prevents adverse outcomes in thrombophilic women. We investigated the effect of LMWH on the pregnancy outcome, on maternal blood pressure values, and on uteroplacental flow in ACE DD nonthrombophilic women with history of preeclampsia. Eighty nonthrombophilic ACE DD women were randomized in 2 groups: 41 treated with dalteparin 5000 IU/day and 39 untreated (control group). Women underwent 24-hour automated blood pressure monitoring in the preconceptional period and every 2 weeks from weeks 8 to 36 and transabdominal color flow/pulsed Doppler examination at weeks 16, 20, and 24. LMWH reduced the risk of clinical negative outcomes (74.1% reduction of preeclampsia and 77.5% reduction of fetal growth restriction) and the severity (88.3% reduction of early onset of preeclampsia and 86.4% reduction of early onset of fetal growth restriction). In treated women, the relative risk for preeclampsia was 0.26 (P=0.02), and the relative risk for fetal growth restriction was 0.14 (P<0.001). Systolic (P=0.002) and diastolic (P=0.002) blood pressures, as well as awake (P=0.04) and asleep (P=0.01) period values, and the resistance indexes of both uterine arteries (P=0.002) were lower in the treated group. LMWH reduces the recurrence of preeclampsia, of negative outcomes, and the resistance of uteroplacental flow, and also prevents maternal blood pressure increase in ACE DD homozygote women with a previous history of preeclampsia.

Key words: heparin • angiotensin-converting enzyme • preeclampsia

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