DALLAS – The drug 17-hydroxyprogesterone caproate, or 17P, is not effective for reducing the risk of preterm delivery in nulliparous women with a cervix length less than the 10th percentile, findings from a randomized placebo-controlled study involving 657 women have shown.
Based on findings from prior studies, 17P is indicated in women with a cervical length of 10-20 mm, which represents only a very small proportion of patients. The objective of the current study was to determine if the benefits of 17P might extend to those with a "longer short cervix," Dr. William Grobman said at the annual meeting of the Society for Maternal-Fetal Medicine.
"Using a cervical length cutoff of the 10th percentile potentially expands the benefits of progesterone to a larger proportion of the population," said Dr. Grobman of the department of obstetrics and gynecology at Northwestern University, Chicago, who was speaking on behalf of the National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network.
Between 16 and 22 weeks’ gestation, when routine anatomic surveys are performed, the 10th percentile for cervical length is 30 mm, he explained.
Of 15,436 women screened at the 14 centers that are part of the Maternal-Fetal Medicine Units Network, 1,588 had a cervical length of less than 30 mm, and 657 consented to randomization. The frequency of preterm birth, defined as delivery prior to 37 weeks’ gestation, was 25.1% in 327 women randomized to receive 17P, and 24.5% in the 330 who received placebo.
There also were no differences in the rates of preterm birth at less than 32 weeks and less than 28 weeks, and no difference in the survival curve – defined as the number of days the women remained pregnant following 17P injection, Dr. Grobman said.
Based on these findings, enrollment in the study was stopped at the third interim analysis, he noted.
As for neonatal outcomes, no difference was seen between the treatment and placebo groups in regard to a composite outcome including, but not limited to, respiratory distress syndrome, bronchopulmonary dysplasia, necrotizing enterocolitis, sepsis, retinopathy of prematurity, and perinatal death.
When neonatal outcomes were analyzed individually, a significant difference was seen between the treatment and placebo groups with regard to sepsis; those in the 17P group had a lower risk of developing sepsis, Dr. Grobman noted.
Women in this study had a singleton pregnancy, and were screened between 16 and 223/7 weeks by a certified sonographer. They had no major fetal anomalies, no increased probability of indicated preterm birth, and no prior loop electrosurgical excision procedure or müllerian anomalies.
Those who consented to participate received an injection of 1 mL of placebo, and those who returned at least 3 days later but before 23 weeks’ gestation were randomized to receive 250 mg of intramuscular 17P weekly, or identically appearing placebo. All received weekly injections until delivery or 37 weeks.
Those in the treatment group were slightly, but significantly older. All other characteristics, including body mass index, race/ethnicity, and estimated gestational age at randomization were similar in the treatment and placebo groups.
The mean cervical length was 24 mm in both groups; less than 10% had a cervical length less than 15 mm, and less than 20% of those had the cervical funnel visualized, Dr. Grobman said.
"Based on these data, we do conclude that weekly intramuscular 17P does not reduce the frequency of preterm birth in nulliparous women with a cervix less than 30 mm," he concluded.
"This is really a study more than anything of women with a longer short cervix," he added, explaining during a question and answer session that the study isn’t powered to look at outcomes for those with other cervical lengths, for example, less than 20 mm or less than 15 mm. About 85% of women in this study had a cervical length between 25 and 30 mm.
Dr. Grobman said he had no relevant financial disclosures.