419 Preterm delivery is a leading cause of neonatal mor- bidity and mortality. It is directly responsible for 75% to 95% of all neonatal deaths not resulting from lethal con- genital malformations. 1,2 Of the survivors, 10% to 15% have significant handicaps. 2,3 According to the World Health Organization, a preterm birth is defined as birth before 37 completed weeks of gestation. 4 In developed countries, the incidence of preterm birth is about 7% to 12% of all deliveries, 5,6 and among these one third occur before 34th week. 1 The incidence of pre- term birth in developing countries is higher than in de- veloped countries. 1,7,8 In Brazil, preterm birth is a public health problem because of the striking social differences in the population. Because of the high prevalence of high-risk pregnancies, the incidence of preterm birth at Hospital das Clinicas, University of Sao Paulo Medical School, is 22.5%, and half of these resulted from sponta- neous preterm labor. Thus, the prevention of preterm de- livery has become one of the major objectives of perinatal medicine. Primary prevention is desirable but not always possi- ble. 5,9 The difficulties are due to unawareness of the cause and pathophysiologic mechanisms of preterm birth, and furthermore, it is not only a medical problem, but also a social and educational problem. The early detection of pregnant women at high risk for preterm delivery 10-14 could be the best way to prevent preterm birth. Thereby, bed rest, cervical cerclage, 15 bac- terial vaginosis treatment, and prophylactic use of pro- gesterone could be one of the managements in this high-risk population. Recent studies have shown that an increase in the num- ber of uterine contractions precedes the onset of preterm labor, 13,16,17 and the frequency of uterine contractions in pregnancies with preterm delivery is higher than in women with term and postterm delivery. 18 Progesterone is useful in allowing pregnancy to reach its physiologic term because at sufficient levels in the myo- From the Obstetrics Clinic, University of São Paulo Medical School. Supported by FAPESP. Received for publication January 9, 2002; revised June 12, 2002; ac- cepted September 11, 2002. Reprint requests: Eduardo B. da Fonseca, MD, University of Sao Paulo Medical School, Obstetric Clinic, Av 11 de junho, 1006 apto 133, Vila Clementino, Sao Paulo–SP, 04041-003, Brazil. E-mail: riedu@uol.com.br © 2003, Mosby, Inc. All rights reserved. 000-9278/2003 $30.00 + 0 doi:10.1067/mob.2003.41 Prophylactic administration of progesterone by vaginal suppository to reduce the incidence of spontaneous preterm birth in women at increased risk: A randomized placebo-controlled double-blind study Eduardo B. da Fonseca, MD, Roberto E. Bittar, PhD, MD, Mario H. B. Carvalho, MD, and Marcelo Zugaib, PhD, MD Sao Paulo, Brazil OBJECTIVE: The purpose of this study was to evaluate the effect of prophylactic vaginal progesterone in de- creasing preterm birth rate in a high-risk population. STUDY DESIGN: A randomized, double-blind, placebo-controlled study included 142 high-risk singleton pregnancies. Progesterone (100 mg) or placebo was administered daily by vaginal suppository and all pa- tients underwent uterine contraction monitoring with an external tocodynamometer once a week for 60 min- utes, between 24 and 34 weeks of gestation. Progesterone (n = 72) and placebo (n = 70) groups were compared for epidemiologic characteristics, uterine contraction frequency, and incidence of preterm birth. Data were compared by χ 2 analysis and Fisher exact test. RESULTS: The preterm birth rate was 21.1% (30/142). Differences in uterine activity were found between the progesterone and placebo groups (23.6% vs 54.3%, respectively; P < .05) and in preterm birth between progesterone and placebo (13.8% vs 28.5%, respectively; P < .05). More women were delivered before 34 weeks in the placebo group (18.5%) than in the progesterone group (2.7%) (P < .05). CONCLUSION: Prophylactic vaginal progesterone reduced the frequency of uterine contractions and the rate of preterm delivery in women at high risk for prematurity. (Am J Obstet Gynecol 2003;188:419-24.) Key words: Preterm delivery, preterm birth, prevention, progesterone