Prevention of Premature Delivery
Prevention of Premature Births with Supplemental Progesterone
What is the problem and what is known about it so far?
Preterm delivery is when a woman gives birth before 37 weeks of pregnancy. It is the leading cause of infant illness and death. Despite knowing a woman is at increased risk for preterm delivery (such as preterm birth in a prior pregnancy), no preventative treatments have been proven effective in the prevention of preterm birth in the next pregnancy.
Why did the researchers do this particular study?
Progesterone is an essential hormone for successful pregnancy, acting as a relaxing agent for the muscle in the uterus (womb). The placenta manufactures the progesterone during the entire pregnancy. Although the exact sequence of events that leads to the onset of labor remains unknown, reduction of the relaxing effects of effect of progesterone is accepted to be an important part of the onset of labor. The theory behind this study is that more progesterone will help with more relaxation of the uterus and less preterm labor. The authors developed this study to determine whether giving progesterone to women with a history of preterm delivery would reduce the chance of having a preterm delivery in the next pregnancy.
Who was studied?
Pregnant women who experienced a preterm delivery in the past were invited to join the study 463 women volunteered.
How was the study done?
Women were randomly assigned to receive a weekly shot which contained either progesterone or placebo (castor oil in a pill that looked similar to that containing the progesterone). Neither the patient nor the researchers knew which medication was administered. Patients received weekly injections from the time of enrollment (between 16 and 20 weeks) until the patient delivered or reached 36 weeks gestation.
What did the researchers find?
The risk of preterm delivery (before 37 weeks) was less in the women who received progesterone (36%) compared to those who received the placebo (55%). This decrease in preterm birth rate was found not only for births before 37 weeks, but also for births before 35 or 32 weeks. Progesterone had no effect on the percentage of women who had symptoms (15%) or treatment (16%) for preterm labor. Fewer women receiving progesterone had an infant with birthweight less than 5 ½ pounds.
What were the limitations of the study?
There are two major limitations in this study which need to be clarified before widespread treatment with progesterone is recommended. First, the two groups should have had a similar history of preterm birth in prior pregnancies. By chance, the women that received placebo had more prior preterm births than the women that received progesterone. The more preterm births a woman has had in the past, the more likely she is to have another preterm birth. Therefore, there is concern that the women given the placebo were at a higher risk for preterm birth in the current pregnancy than the women receiving progesterone. The second concern was that the rate of preterm birth in the placebo group was much higher than expected. The expected preterm birth rate for women receiving placebo was about 37%; the observed preterm birth rate in the group that received progesterone was 36% and in the placebo group 55%. There were concerns that the castor oil used as a placebo might have increased the preterm birth rate, leading to the false conclusion that the progesterone was beneficial.
What are the implications of the study?
A trial using a different placebo needs to be completed before progesterone can be routinely recommended to prevent preterm delivery. Progesterone supplementation may be considered in women at very high risk for preterm birth, although questions remain regarding the usefulness of this approach.
Summarized by Anna Benvenuto, College of Medicine, University of Vermont.
Summarized from "Prevention of Recurrent Preterm Delivery by 17 Alpha- Hydroxyprogesterone Caproate". Meis PJ et al. The New England Journal of Medicine. June 12, 2003, Volume 348, Number 24, pages 2379-2385.
