Prevention of Recurrent Preterm Delivery by 17 Alpha-Hydroxyprogesterone Caproate
Paul J. Meis, M.D., Mark Klebanoff, M.D., Elizabeth Thom, Ph.D., Mitchell P. Dombrowski, M.D., Baha Sibai, M.D., Atef H. Moawad, M.D., Catherine Y. Spong, M.D., John C. Hauth, M.D., Menachem Miodovnik, M.D., Michael W. Varner, M.D., Kenneth J. Leveno, M.D., Steve N. Caritis, M.D., Jay D. Iams, M.D., Ronald J. Wapner, M.D., Deborah Conway, M.D., Mary J. O'Sullivan, M.D., Marshall Carpenter, M.D., Brian Mercer, M.D., Susan M. Ramin, M.D., John M. Thorp, M.D., Alan M. Peaceman, M.D., for the National Institute of Child Health and Human Development Maternal–Fetal Medicine Units Network
Background Women who have had a spontaneous preterm deliveryare at greatly increased risk for preterm delivery in subsequentpregnancies. The results of several small trials have suggestedthat 17 alpha-hydroxyprogesterone caproate (17P) may reducethe risk of preterm delivery.
Methods We conducted a double-blind, placebo-controlled trialinvolving pregnant women with a documented history of spontaneouspreterm delivery. Women were enrolled at 19 clinical centersat 16 to 20 weeks of gestation and randomly assigned by a centraldata center, in a 2:1 ratio, to receive either weekly injectionsof 250 mg of 17P or weekly injections of an inert oil placebo;injections were continued until delivery or to 36 weeks of gestation.The primary outcome was preterm delivery before 37 weeks ofgestation. Analysis was performed according to the intention-to-treatprinciple.
Results Base-line characteristics of the 310 women in the progesteronegroup and the 153 women in the placebo group were similar. Treatmentwith 17P significantly reduced the risk of delivery at lessthan 37 weeks of gestation (incidence, 36.3 percent in the progesteronegroup vs. 54.9 percent in the placebo group; relative risk,0.66 [95 percent confidence interval, 0.54 to 0.81]), deliveryat less than 35 weeks of gestation (incidence, 20.6 percentvs. 30.7 percent; relative risk, 0.67 [95 percent confidenceinterval, 0.48 to 0.93]), and delivery at less than 32 weeksof gestation (11.4 percent vs. 19.6 percent; relative risk,0.58 [95 percent confidence interval, 0.37 to 0.91]). Infantsof women treated with 17P had significantly lower rates of necrotizingenterocolitis, intraventricular hemorrhage, and need for supplementaloxygen.
Conclusions Weekly injections of 17P resulted in a substantialreduction in the rate of recurrent preterm delivery among womenwho were at particularly high risk for preterm delivery andreduced the likelihood of several complications in their infants.
Source Information
From Wake Forest University, Winston-Salem, N.C. (P.J.M.); the National Institute of Child Health and Human Development, Bethesda, Md. (M.K., C.Y.S.); the Biostatistics Center, George Washington University, Rockville, Md. (E.T.); Wayne State University, Detroit (M.P.D.); the University of Tennessee, Memphis (B.S.); the University of Chicago, Chicago (A.H.M.); the University of Alabama, Birmingham (J.C.H.); the University of Cincinnati, Cincinnati, and Columbia University, New York (M.M.); the University of Utah, Salt Lake City (M.W.V.); the University of Texas Southwestern Medical Center, Dallas (K.J.L.); the University of Pittsburgh, Pittsburgh (S.N.C.); Ohio State University, Columbus (J.D.I.); Thomas Jefferson University, Philadelphia (R.J.W.); the University of Texas, San Antonio (D.C.); the University of Miami, Miami (M.J.O.); Brown University, Providence, R.I. (M.C.); Case Western Reserve University, Cleveland (B.M.); the University of Texas, Houston (S.M.R.); the University of North Carolina, Chapel Hill (J.M.T.); and Northwestern University, Chicago (A.M.P.).
Address reprint requests to Dr. Meis at the Department of Obstetrics and Gynecology, Wake Forest University, Medical Center Blvd., Winston-Salem, NC 27157, or at pmeis{at}wfubmc.edu.
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