Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone caproate.
BACKGROUND
Women who have had a spontaneous preterm delivery are at greatly increased risk for preterm delivery in subsequent pregnancies. The results of several small trials have suggested that 17 alpha-hydroxyprogesterone caproate (17P) may reduce the risk of preterm delivery.


METHODS
We conducted a double-blind, placebo-controlled trial involving pregnant women with a documented history of spontaneous preterm delivery. Women were enrolled at 19 clinical centers at 16 to 20 weeks of gestation and randomly assigned by a central data center, in a 2:1 ratio, to receive either weekly injections of 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 of gestation. Analysis was performed according to the intention-to-treat principle.


RESULTS
Base-line characteristics of the 310 women in the progesterone group and the 153 women in the placebo group were similar. Treatment with 17P significantly reduced the risk of delivery at less than 37 weeks of gestation (incidence, 36.3 percent in the progesterone group vs. 54.9 percent in the placebo group; relative risk, 0.66 [95 percent confidence interval, 0.54 to 0.81]), delivery at less than 35 weeks of gestation (incidence, 20.6 percent vs. 30.7 percent; relative risk, 0.67 [95 percent confidence interval, 0.48 to 0.93]), and delivery at less than 32 weeks of gestation (11.4 percent vs. 19.6 percent; relative risk, 0.58 [95 percent confidence interval, 0.37 to 0.91]). Infants of women treated with 17P had significantly lower rates of necrotizing enterocolitis, intraventricular hemorrhage, and need for supplemental oxygen.


CONCLUSIONS
Weekly injections of 17P resulted in a substantial reduction in the rate of recurrent preterm delivery among women who were at particularly high risk for preterm delivery and reduced the likelihood of several complications in their infants.
Meis
Paul J
PJ
Department of Obstetrics and Gynecology, Wake Forest University, Winston-Salem, NC 27157, USA. pmeis@wfubmc.edu
Klebanoff
Mark
M
Thom
Elizabeth
E
Dombrowski
Mitchell P
MP
Sibai
Baha
B
Moawad
Atef H
AH
Spong
Catherine Y
CY
Hauth
John C
JC
Miodovnik
Menachem
M
Varner
Michael W
MW
Leveno
Kenneth J
KJ
Caritis
Steve N
SN
Iams
Jay D
JD
Wapner
Ronald J
RJ
Conway
Deborah
D
O'Sullivan
Mary J
MJ
Carpenter
Marshall
M
Mercer
Brian
B
Ramin
Susan M
SM
Thorp
John M
JM
Peaceman
Alan M
AM
Gabbe
Steven
S
D000077713:17 alpha-Hydroxyprogesterone Caproate; D000328:Adult; D001724:Birth Weight; D002543:Cerebral Hemorrhage / Q000453:epidemiology; D004311:Double-Blind Method; D020345:Enterocolitis, Necrotizing / Q000453:epidemiology; D005260:Female; D006801:Humans; D006908:Hydroxyprogesterones / Q000009:adverse effects / Q000627:therapeutic use*; D007231:Infant, Newborn; D007234:Infant, Premature; D007752:Obstetric Labor, Premature / Q000517:prevention & control*; D010102:Oxygen Inhalation Therapy; D011247:Pregnancy; D011256:Pregnancy Outcome; D045167:Progesterone Congeners / Q000009:adverse effects / Q000627:therapeutic use*; D012306:Risk; D016019:Survival Analysis
D006908:Hydroxyprogesterones; D045167:Progesterone Congeners; D000077713:17 alpha-Hydroxyprogesterone Caproate