SAN FRANCISCO — The use of high-dose progesterone in women at risk for preterm delivery following premature labor slows the progression of cervical changes linked to early delivery, Dr. Fabio Facchinetti said at the annual meeting of the Society for Maternal-Fetal Medicine.
In a randomized controlled trial, the use of 17 α-hydroxyprogesterone caproate (17-OHPC) was associated with reduced cervical shortening and local inflammation, which led to a significantly reduced incidence of preterm deliveries, said Dr. Facchinetti of Universita di Modena e Reggio Emilia in Modena, Italy.
To investigate the mechanism of action of 17-OHPC in preventing preterm delivery, Dr. Facchinetti and colleagues randomized 45 hospitalized women who remained undelivered after an episode of preterm labor between 25 and 33 weeks to observation only or to treatment with twice weekly intramuscular injections of 341 mg of 17-OHPC until 36 weeks. The typical dose of 17-OHPC in these cases is usually a single weekly injection.
Dr. Facchinetti cited two reasons for the high dose: the cervical inflammatory processes were already underway and needed to be stalled; and the treatment was started later in pregnancy so there was less time for efficacy.
All of the women had singleton pregnancies, intact membranes, and cervical dilatation less than 2 cm. Those with chronic disease, gestational disease, large or multiple uterine myomas, or suspected intraamniotic infection were excluded. There were differences between the 23 women in the treatment group and the 22 controls in terms of maternal age or gestational age at time of preterm labor (mean 29 weeks), and the majority of patients had sonographic evidence of a short cervix at baseline, Dr. Facchinetti reported. All of the women received two doses of intramuscular betamethasone 24 hours apart to promote fetal lung development, as per hospital policy.
After randomization 4–6 days following hospital admission for preterm labor, each subject underwent a cervical swab and ultrasound measurement of cervical length at baseline, 1 week, and 3 weeks.
In terms of clinical outcome, 22% of the women in the treatment group had preterm delivery (before week 37), compared with 54% in the observation group, representing a statistically significant reduction, said Dr. Facchinetti. Among women in the treatment group, the mean length of pregnancy was 9 days longer than in the control group.
An analysis of the primary study outcome—change in cervical length—demonstrated significant differences between the treatment and observation groups. “After 3 weeks, women treated with 17-OHPC had a median 2-mm reduction in cervical length compared with 4 mm in untreated women,” he said. “Our speculation is that preterm cervical ripening is the real driver of preterm delivery and can be blocked by [17-OHPC].”