Obstetricians face the potential practice dilemma of having withdrawn from the market the only drug approved by the US Food and Drug Administration (FDA) for the prevention of preterm birth in women with a singleton pregnancy who have a history of singleton spontaneous preterm birth. In the recently published PROLONG (Progestin's Role in Optimizing Neonatal Gestation) study by Blackwell and colleagues, the trial results revealed that there were no significant differences in preterm birth between women treated with 17 α-hydroxyprogesterone caproate (17P; Makena) and those who received placebo.1 For study details and comments, see "Progesterone supplementation does not PROLONG pregnancy in women at risk for preterm birth: What do we do now?" by Michael House, MD, and Errol Norwitz, MD, PhD, MBA. Subsequently, the FDA's Bone, Reproductive and Urologic Drugs Advisory Committee voted 9-7 to recommend pursuit of approval withdrawal for 17P.
To assess how experienced obstetricians would manage women with previous preterm birth if 17P became unavailable, OBG Management conducted an informal survey. Here, 4 experts respond to the question, "What are you going to do in your practice for women with a history of a previous preterm birth if 17P is no longer an option?"
Not ready to leave behind 17P for recurrent preterm delivery
Patrick Duff, MD
Preterm delivery is arguably the most important problem in perinatal medicine. It occurs in 10% to 12% of all obstetric patients in the United States, and complications of prematurity account for the majority of neonatal deaths. A major risk factor for recurrent preterm delivery is a prior history of spontaneous preterm delivery, with or without preterm premature rupture of membranes. Clearly, prevention of recurrence is of paramount importance.
In the Maternal-Fetal Medicine Units (MFMU) Network trial, Meis and colleagues demonstrated a 34% reduction (relative risk [RR], 0.66; 95% confidence interval [CI], 0.54-0.81) in the risk of recurrent preterm delivery in women who received weekly 250-mg injections of 17P (also called 17-OHPC). After publication of that trial, use of 17P became accepted practice in the United States.2
The PROLONG study by Blackwell and colleagues questions the value of 17P.1 In that international trial, which included 1,708 women from 41 centers in the United States and 52 outside the United States, the authors were unable to show any significant difference in the frequency of preterm delivery < 35 weeks (11.0% in the women receiving 17P and 11.5% in women receiving placebo; RR, 0.95; 95% CI, 0.71-1.26). Even when they examined the subset of women treated at US medical centers, they could not demonstrate any significant difference in treatment outcome.
At least 2 major explanations account for the discrepancy between the MFMU and the Blackwell studies. First, the participants in the PROLONG trial were clearly not at the same increased risk for recurrent preterm delivery as those in the MFMU trial. Second, in the PROLONG trial only the minority of participants were from the United States. In fact, given the relatively low rate of recurrent preterm delivery in the PROLONG trial, the study was underpowered to detect meaningful differences in maternal outcome. Therefore, I am not ready to abandon the use of progesterone supplementation in women at risk for recurrent preterm delivery.
Continue to: If the FDA removes 17P from the market...