Does Progesterone Treatment Influence Risk Factors for Recurrent Preterm Delivery? Paul J. Meis, MD, Mark Klebanoff, MD, Mitchell P. Dombrowski, MD, Baha M. Sibai, MD, Sharon Leindecker, MS, MBA, Atef H. Moawad, MD, Allison Northen, RN, Jay D. Iams, MD, Michael W. Varner, MD, Steve N. Caritis, MD, Mary J. O’Sullivan, MD, Menachem Miodovnik, MD, Kenneth J. Leveno, MD, Deborah Conway, MD, Ronald J. Wapner, MD, Marshall Carpenter, MD, Brian Mercer, MD, Susan M. Ramin, MD, John M. Thorp, MD, Alan M. Peaceman, MD, Steven Gabbe, MD, for the National Institute of Child Health and Human Development Maternal– Fetal Medicine Units Network* Objective: To examine how demographic and pregnancy characteristics can affect the risk of recurrent preterm delivery and the how the effectiveness of progesterone treatment for prevention alters these relationships. Methods: This was a secondary analysis of a randomized trial of 17-hydroxyprogesterone caproate to prevent recur- rent preterm delivery in women at risk. Associations of risk factors for preterm delivery (less than 37 completed weeks of gestation) were examined separately for the women in the 17-hydroxyprogesterone caproate (n = 310) and placebo (n = 153) groups. Results: Univariate analysis found that the number of previous preterm deliveries and whether the penultimate delivery was preterm were significant risk factors for pre- term delivery in both the placebo and progesterone groups. High body mass index was protective of preterm birth in the placebo group. Multivariate analysis found progesterone treatment to cancel the risk of more than 1 previous preterm delivery, but not the risk associated with the penultimate pregnancy delivered preterm. Obesity was associated with lower risk for preterm delivery in the placebo group but not in the women treated with progesterone. Conclusion: The use of 17-hydroxyprogesterone ca- proate in women with a previous preterm delivery reduces the overall risk of preterm delivery and changes the epide- miology of risk factors for recurrent preterm delivery. In particular, these data suggest that 17-hydroxyprogester- one caproate reduces the risk of a history of more than 1 preterm delivery. (Obstet Gynecol 2005;106:557–561) Level of Evidence: I A pproximately 10% of all pregnancies in the United States end in preterm birth, and this 10% accounts for approximately 70% of the perinatal deaths and one half of long-term neurologic morbid- ity. 1 Furthermore, the rates of preterm birth have been increasing in the United States in the past decades. 2 Preterm birth is thought to have many different causes. Attempts to elucidate these causes by examining the epidemiology of preterm birth have *For a list of other members of the National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network, see the Appendix. From the National Institute of Child Health and Human Development, Rockville, Maryland; Biostatistics Center, George Washington University, Rockville, Maryland; Division of Maternal-Fetal Medicine, University of Alabama, Birmingham, Alabama; and Departments of Obstetrics and Gynecol- ogy, Division of Maternal–Fetal Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina; Wayne State University, Detroit, Michigan; University of Tennessee, Memphis, Tennessee; University of Chicago, Chicago, Illinois; Ohio State University. Columbus, Ohio; University of Utah, Salt Lake City, Utah; University of Pittsburgh, Pittsburgh, Pennsylvania; University of Miami, Miami, Florida; University of Cincinnati, Cincinnati, Ohio; University of Texas Southwest, Dallas, Texas; University of Texas at San Antonio, San Antonio, Texas; Drexel University, Philadelphia, Pennsylvania; Brown University, Providence, Rhode Island; Case Western Reserve University, Cleveland, Ohio; University of Texas, Houston, Texas; University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Northwestern Univer- sity, Chicago, Illinois; and Vanderbilt University, Nashville, Tennessee. Supported by grants from the National Institute of Child Health and Human Development (HD27860, HD36801, HD27917, HD21414, HD27861, HD27869, HD27905, HD34208, HD34116, HD21410, HD27915, HD34136, HD34210, HD34122, HD40500, HD40560, HD40512, HD34210, HD40544, MO1-RR-000080). Corresponding author: Paul J. Meis, MD, Department of Obstetrics and Gynecology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157; e-mail: pmeis@wfubmc.edu. © 2005 by The American College of Obstetricians and Gynecologists. Published by Lippincott Williams & Wilkins. ISSN: 0029-7844/05 VOL. 106, NO. 3, SEPTEMBER 2005 OBSTETRICS & GYNECOLOGY 557