Original Article Progesterone Does Not Prevent Preterm Births in Women with Twins Christian M. Briery, MD, Edward W. Veillon, MD, Chad K. Klauser, MD, Rick W. Martin, MD, Suneet P. Chauhan, MD, Everett F. Magann, MD, and John C. Morrison, MD Objective: To compare preterm birth rate and neonatal outcome in twin gestations randomized to either 17 alpha-hydroxyprogesterone caproate (17P) or placebo. Materials and Methods: Women with twin gestations between 20 –30 weeks were randomized to receive weekly injections of either 250mg 17P injection (Group I), or placebo (Group II). Maternal and neonatal outcome data was recorded. Results: Thirty twin intrauterine pregnancies were randomized; 16 received 17P and 14 received placebo. Demographic data as well as past history and gestational age at randomization were equivalent be- tween groups (P = 0.286 – 0.847). All patients in both groups were Medicaid recipients. The incidence of preterm labor (P = 0.980), and premature rupture of the membranes (P = 0.525) were the same be- tween groups. Gestational age at delivery was also similar between 17P (33.9 weeks) versus placebo (33.1 weeks, P = 0.190) as was the inci- dence of preterm birth 35 weeks (44% vs 79%, P = 0.117). Infant weight (P = 0.641), Apgar score at 5 minutes (P = 0.338) as well as neonatal morbidity such as respiratory distress syndrome (P = 0.838), patent ductus arteriosus (P = 0.704), intraventricular hemorrhage (P = 0.851) and necrotizing enterocolitis (P = 0.946) showed no difference. Days spent in the NICU among 17P (18.4) versus placebo (17.3, P = 0.155), neonatal death (P = 0.359) and those infants discharged with neurologic handicap (P = 0.594) were not different between groups. Conclusion: Amongst this group of twin gestations weekly 17HP injections did not reduce the incidence of preterm birth or the com- plications associated with prematurity. Key Words: preterm birth, progesterone, twins P revention of preterm birth remains an unsolved compli- cation of pregnancy as the rate of deliveries at 37 weeks’ gestation continues to rise, with associated complications ac- counting for 75% of newborn morbidity. 1 Supplemental pro- gesterone therapy and its synthetic analogs used to improve reproductive outcome have been studied for many years with mixed results. 2 Keirse 2 performed a comprehensive meta- analysis reviewing 17 alpha-hydroxyprogesterone caproate (17P) administration and suggested that if progesterone was used in the appropriate patient group it might prevent preterm delivery. This led to randomized clinical trials enrolling women with prior spontaneous preterm births, which showed that 17P or vaginal progesterone did indeed reduce the num- ber of preterm deliveries. 3,4 A more recent meta-analysis as- sessing 10 clinical trials in singleton pregnancy rendered the same conclusion, and the use of 17P among obstetricians has become common for this indication. 5 Preterm delivery among twin gestations averages almost 50% 6 and accounts for one quarter of births 35 weeks, and up to 10% of 32 weeks’ gestation. 7 While the pathophysi- ologic mechanism of preterm labor in twins appears to be overdistention, some clinicians have suggested administering progesterone in an effort to prolong pregnancy and prevent preterm birth. Also, progesterone withdrawal is associated From the University of TN Chattanooga Unit, Chattanooga, TN; Department of Obstetrics and Gynecology, University of Mississippi Medical Center, Jackson, MS; Mount Sinai Medical Center, New York City, NY; and Aurora Healthcare, West Allis, WI. Address for correspondence: John C. Morrison, MD, Department of Obstetrics and Gynecology, University of Mississippi Medical Center, 2500 North State Street, Jackson, Mississippi 39216-4505. Email: jmorrison@ob-gyn. umsmed.edu PharmAmerica donated generously 17 hydroxyprogesterone. Accepted February 13, 2009. Copyright © 2009 by The Southern Medical Association 0038-4348/0-2000/10200-0900 Key Points • Twin pregnancies treated with weekly 17-alphahy- droxyprogesterone (17P) injections do not have in- creased gestational age at delivery nor a reduction in preterm births compared to other women with twin pregnancies who received placebo injections. • Weekly treatment with 17P did not reduce neonatal complications associated with prematurity including death, nor did it decrease neonatal intensive care unit stay. • Twin gestations do not benefit from 17P injections in terms of a reduction of the incidence of preterm birth or neonatal complications. 900 © 2009 Southern Medical Association