title: Vaginal progesterone reduces the rate of preterm birth in women with a sonographic short cervix: a multicenter, randomized, double-blind, placebo-controlled trial.
abstract: OBJECTIVE
  Women with a sonographic short cervix in the mid-trimester are at increased risk for preterm delivery. This study was undertaken to determine the efficacy and safety of using micronized vaginal progesterone gel to reduce the risk of preterm birth and associated neonatal complications in women with a sonographic short cervix.
  
  
  METHODS
  This was a multicenter, randomized, double-blind, placebo-controlled trial that enrolled asymptomatic women with a singleton pregnancy and a sonographic short cervix (10-20 mm) at 19 + 0 to 23 + 6 weeks of gestation. Women were allocated randomly to receive vaginal progesterone gel or placebo daily starting from 20 to 23 + 6 weeks until 36 + 6 weeks, rupture of membranes or delivery, whichever occurred first. Randomization sequence was stratified by center and history of a previous preterm birth. The primary endpoint was preterm birth before 33 weeks of gestation. Analysis was by intention to treat.
  
  
  RESULTS
  Of 465 women randomized, seven were lost to follow-up and 458 (vaginal progesterone gel, n=235; placebo, n=223) were included in the analysis. Women allocated to receive vaginal progesterone had a lower rate of preterm birth before 33 weeks than did those allocated to placebo (8.9% (n=21) vs 16.1% (n=36); relative risk (RR), 0.55; 95% CI, 0.33-0.92; P=0.02). The effect remained significant after adjustment for covariables (adjusted RR, 0.52; 95% CI, 0.31-0.91; P=0.02). Vaginal progesterone was also associated with a significant reduction in the rate of preterm birth before 28 weeks (5.1% vs 10.3%; RR, 0.50; 95% CI, 0.25-0.97; P=0.04) and 35 weeks (14.5% vs 23.3%; RR, 0.62; 95% CI, 0.42-0.92; P=0.02), respiratory distress syndrome (3.0% vs 7.6%; RR, 0.39; 95% CI, 0.17-0.92; P=0.03), any neonatal morbidity or mortality event (7.7% vs 13.5%; RR, 0.57; 95% CI, 0.33-0.99; P=0.04) and birth weight < 1500 g (6.4% (15/234) vs 13.6% (30/220); RR, 0.47; 95% CI, 0.26-0.85; P=0.01). There were no differences in the incidence of treatment-related adverse events between the groups.
  
  
  CONCLUSIONS
  The administration of vaginal progesterone gel to women with a sonographic short cervix in the mid-trimester is associated with a 45% reduction in the rate of preterm birth before 33 weeks of gestation and with improved neonatal outcome.
authors.affiliation: Perinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development/National Institutes of Health/Department of Health and Human Services, Bethesda, MD, USA.
authors.forename: S S
authors.initials: SS
authors.lastname: Hassan
authors.forename: R
authors.initials: R
authors.lastname: Romero
authors.forename: D
authors.initials: D
authors.lastname: Vidyadhari
authors.forename: S
authors.initials: S
authors.lastname: Fusey
authors.forename: J K
authors.initials: JK
authors.lastname: Baxter
authors.forename: M
authors.initials: M
authors.lastname: Khandelwal
authors.forename: J
authors.initials: J
authors.lastname: Vijayaraghavan
authors.forename: Y
authors.initials: Y
authors.lastname: Trivedi
authors.forename: P
authors.initials: P
authors.lastname: Soma-Pillay
authors.forename: P
authors.initials: P
authors.lastname: Sambarey
authors.forename: A
authors.initials: A
authors.lastname: Dayal
authors.forename: V
authors.initials: V
authors.lastname: Potapov
authors.forename: J
authors.initials: J
authors.lastname: O'Brien
authors.forename: V
authors.initials: V
authors.lastname: Astakhov
authors.forename: O
authors.initials: O
authors.lastname: Yuzko
authors.forename: W
authors.initials: W
authors.lastname: Kinzler
authors.forename: B
authors.initials: B
authors.lastname: Dattel
authors.forename: H
authors.initials: H
authors.lastname: Sehdev
authors.forename: L
authors.initials: L
authors.lastname: Mazheika
authors.forename: D
authors.initials: D
authors.lastname: Manchulenko
authors.forename: M T
authors.initials: MT
authors.lastname: Gervasi
authors.forename: L
authors.initials: L
authors.lastname: Sullivan
authors.forename: A
authors.initials: A
authors.lastname: Conde-Agudelo
authors.forename: J A
authors.initials: JA
authors.lastname: Phillips
authors.forename: G W
authors.initials: GW
authors.lastname: Creasy
mesh_terms: D000282:Administration, Intravaginal; D000293:Adolescent; D000328:Adult; D002584:Cervix Uteri / Q000000981:diagnostic imaging / Q000187:drug effects*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D010919:Placebos; D011247:Pregnancy; D011256:Pregnancy Outcome; D018566:Pregnancy, High-Risk; D047928:Premature Birth / Q000188:drug therapy* / Q000517:prevention & control*; D011374:Progesterone / Q000008:administration & dosage*; D011372:Progestins / Q000008:administration & dosage*; D011446:Prospective Studies; D014463:Ultrasonography; D014621:Vagina / Q000000981:diagnostic imaging / Q000187:drug effects; D014622:Vaginal Creams, Foams, and Jellies / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D010919:Placebos; D011372:Progestins; D014622:Vaginal Creams, Foams, and Jellies; D011374:Progesterone