Published in UAB Insight, Winter 2008
Therapy Neither Prolongs Gestation Nor Improves Fetal Outcomes
Premature birth is a leading cause of infant death and leaves newborns at risk for life-threatening infections, blindness, breathing problems, learning and developmental disabilities, and cerebral palsy. More than half of women pregnant with twins deliver prematurely. The rate of US twin births has increased dramatically since 1980 from 1.9% to 3.2% of all births in 2004.
In 2003 researchers, including UAB obstetrician/gynecologist John C. Hauth, MD, with the Maternal-Fetal Medicine Units Network (MFMU) of the National Institute of Child Health and Human Development (NICHD) reported that weekly injections of 17-alpha hydroxyprogesterone caproate (17P) reduced the risk of preterm birth by 34% among pregnant women with previous preterm births (N Eng J Med. 2003;348:2379-2385 [Erratum, 349:1299]). Many physicians began prescribing the therapy for women pregnant with twins and for other women at risk for preterm birth, such as those with a shortened cervix.
In a recent study by UAB investigators and the MFMU, weekly 250-mg injections of 17P failed to lower the rate of preterm birth, to prolong gestation, or to improve fetal or neonatal outcomes in women pregnant with twins (N Eng J Med. 2007;357:454-461).
UAB obstetrician/gynecologist and principal investigator Dwight J. Rouse, MD, says, “Our study shows progesterone therapy is not appropriate for all women at risk of giving birth prematurely.” Participants were 655 women randomly assigned to receive weekly injections of placebo or 17P. Investigators began injections at 16 to 20 weeks gestation and continued until the 35th week of pregnancy or birth. Delivery before 35 weeks or fetal loss (miscarriage, termination of pregnancy, or stillbirth) occurred in 41.5% of women who received 17P versus 37.3% of women receiving placebo. Whether conception was spontaneous or achieved with assisted reproduction did not affect results, nor did the type of placentation (shared vs separate placentas).
“Progesterone use did not reduce premature birth in twin pregnancies and did not affect the amount of time babies spent in the womb,” Rouse says. “The study did not determine whether progesterone therapy could reduce preterm birth in women pregnant with twins who had experienced previous preterm delivery, because fewer than 10% of women in the trial had experienced such a birth.” Rouse and colleagues enrolled women pregnant with triplets in a concurrent trial, the results of which are being analyzed.
Other Progesterone Trials
Progesterone therapy did improve outcomes in another recent trial. Fonseca et al found daily vaginal administration of 200 mg of progesterone reduced the rate of delivery before 34 weeks from 34% to 19% in women with a short cervix (≤15 mm) (N Eng J Med. 2007;357:462-469).
“Further investigation is warranted to assess whether 17P is effective in other conditions that confer an increased risk of preterm birth,” Rouse says. Researchers are testing progesterone in at least 15 trials recruiting more than 5000 women. One of these trials, which is being conducted at UAB, seeks to determine 17P’s effect on women with a short cervix in their first pregnancy. “These ongoing studies are necessary to clarify benefits of progesterone therapy for prevention of preterm birth and to provide better insight about optimal formulation, dose, and route of delivery,” he says.
For more information:
Dr. Dwight Rouse
1.800.UAB.MIST
mist@uabmc.edu