Possible Efficacy of Vaginal Progesterone on Asymptomatic Women with a Short Cervix after 24 Weeks of Gestation: A Historical Cohort Study in Japan

Abstract

Introduction: Few studies have explored the preventive efficacy of vaginal progesterone (VD) treatment for preterm delivery (PTD) in Japanese clinical practice. In this study, the efficacy of the VD treatment in pregnant women with a short cervix (sCX) diagnosed after 24 weeks is evaluated, focusing on perinatal outcomes.

Methods: A retrospective historical cohort study. Clinical data of 273 singleton women hospitalized for preventing PTD were extracted. Inclusion criteria are diagnosed sCX at 24-33 weeks. We excluded women with factors including treatment start before 24 weeks, medically induced PTD, PTD on admission day, and fetal demise. Consequently, logistic regression analyses were conducted on data from 79 women during Period 1 (November 2015 to March 2018, using prolonged intravenous ritodrine hydrochloride) and 82 women during Period 2 (August 2018 to August 2022, implementing VD treatment), adjusting maternal age, parity, body mass index, gestational age, cervical length, and histological chorioamnionitis. The primary outcomes involved PTD <37 and <34 weeks and neonatal intensive care unit admission. Secondary outcomes included the interval from the diagnosis of sCX to delivery <14 and <28 days, infant intubation, and surfactant administration. Since VD use is off-label in Japan, we obtained written informed consent prior to treatment.

Results: VD treatment (Period 2) significantly decreased the incidence of PTD (birth < 37 weeks) (adjusted odds ratios [ORs] 0.43, 95% confidence intervals [CIs] 0.19-0.96), impending delivery within 14 and 28 days after confirming sCX (adjusted OR 0.12, 95% CI 0.06-0.72; adjusted OR 0.25, 95% CI 0.09-0.74, respectively), and neonatal intubation rate (adjusted OR 0.17, 95% CI 0.04-0.75).

Conclusions: The VD treatment can prevent PTD in asymptomatic women with sCX diagnosed after 24 weeks of gestation. Although further validation is warranted, these findings may contribute to expanding the use of VD treatment in Japanese clinical practice.

Keywords: Cervical insufficiency; Preterm labor; Progesterone; Short cervix.

Figure 1.

Flow diagram of study design. GA, gestational age; PTD, preterm delivery.

Figure 2.

A) Comparison of preterm delivery rates in each period; 24-29 weeks or 30-32 weeks of gestation. The blue bar represents Period 1, and the red bar indicates Period 2. B) Scatterplots depicting the relationship between the number of days of pregnancy extension and the gestational age at which maternal treatment was initiated. The blue circles and line represent the values for each patient and best-fit line in Period 1, whereas the red circles and line indicate those in Period 2. A trend was observed in the correlation coefficients between the two groups, but it was not statistically significant (Fisher’s z transformation; p = 0.099).