Preventing Preterm Birth

The Issue Today

Two additional studies published just this year have addressed the issue of progesterone use in women with two other high-risk conditions: multiple gestations and a short cervix.

The trial of progesterone therapy for twin pregnancy—again using 17P—found no benefit for 17P prophylaxis in a study conducted by the MFMU Network (N. Engl. J. Med. 2007;357:454–61). This suggests to me that the mechanism of early delivery of twins is likely to be somewhat different from the mechanism of early delivery in women with a singleton preterm birth.

The recent trial of progesterone therapy for a short cervix, which was conducted by the Fetal Medicine Foundation in England, reported positive results. In this trial, 250 women with a cervical length of 15 mm or less were randomly assigned to receive vaginal progesterone (not 17P) or placebo (N. Engl. J. Med. 2007;357:462–9).

Spontaneous delivery before 34 weeks' gestation was less frequent in the progesterone group (19%) than in the placebo group (34%).

The exact mode of action of 17P therapy in preventing preterm birth is unknown, but we do know that progesterone does many things. It relaxes the uterus and, we now know, it alters or blunts the body's response to inflammation.

My interpretation of the research to date is that progesterone is effective when inflammation is the key element of the pathway to preterm birth (as is often the case for a short cervix) and that it does not work when uterine stretch and contractions are the critical pathway elements (as in twins).

These and other studies need to be repeated and confirmed, however. The MFMU Network has just begun a study of 17P injections for women with a short cervix who are pregnant for the first time. If it turns out that progesterone really does help prevent premature birth in women with a short cervix, then measurement of the cervix using transvaginal ultrasonography could be a useful test to identify women who might benefit from 17P prophylaxis.

For now, I believe that any woman with a previous spontaneous preterm birth should be informed of progesterone therapy. The higher her risk for recurrence—the earlier her previous preterm birth, for instance, or the higher the number of previous preterm births—the more likely it is that she might benefit from this therapy.

A woman whose previous preterm delivery occurred at 35 weeks' gestation, for instance, may well choose to decline the therapy. My discussions with women who have this history are more of a conversation than a recommendation. On the other hand, a woman with two previous preterm births, both before 32 weeks' gestation, should be strongly urged to have the therapy.

Again, a personal estimate of recurrence risk forms the basis for these recommendations. There are currently no data available to support the use of cervical ultrasound in women with a prior preterm birth to identify women who are more or less likely to benefit from progesterone prophylaxis, so we offer it to any woman with an appropriate history. Someday, we may be able to use progesterone more selectively than we do today.

There is no evidence to suggest that progesterone will help women with preterm labor or ruptured membranes in the current pregnancy, so we do not use it in these women.

Any risks of progesterone therapy are primarily theoretical, based on concern about continuing a pregnancy in which inflammation may favor allowing delivery. Fortunately, there are no signs of that in the original Meis study or in the two more recent large studies in women with twins and a short cervix.

A study recently published of the babies born in the 2003 Meis study found no differences in neurologic development between those who received progesterone and those who took placebo. MFMU Network investigators evaluated the children with various neurologic, physical, and developmental examinations, up to the ages of 4–6 years.

I tell my patients that potential risks continue to be monitored, but that progesterone prophylaxis is backed by a lot more evidence than are many other treatments and practices that are considered “standard” in obstetrics today.

Prematurity is a common and major contributor to the relatively high U.S. infant mortality rate. Therapeutic approaches have been only marginally successful. PhotoDisc, Inc.

Prematurity and Infant Mortality

Infant mortality in the United States was more than 6 per 1,000 live births in 2004, the latest year for which data are available from the Centers for Disease Control and Prevention. This troubling rate places the United States low in the ranking of industrialized nations.