title: Prevention of preterm delivery with vaginal progesterone in women with preterm labour (4P): randomised double-blind placebo-controlled trial.
abstract: OBJECTIVE
  To evaluate the effectiveness of 200 mg of daily vaginal natural progesterone to prevent preterm birth in women with preterm labour.
  
  
  METHODS
  Multicentre, randomised, double-blind, placebo-controlled trial.
  
  
  METHODS
  Twenty-nine centres in Switzerland and Argentina.
  
  
  METHODS
  A total of 385 women with preterm labour (24(0/7) to 33(6/7) weeks of gestation) treated with acute tocolysis.
  
  
  METHODS
  Participants were randomly allocated to either 200 mg daily of self-administered vaginal progesterone or placebo within 48 hours of starting acute tocolysis.
  
  
  METHODS
  Primary outcome was delivery before 37 weeks of gestation. Secondary outcomes were delivery before 32 and 34 weeks, adverse effects, duration of tocolysis, re-admissions for preterm labour, length of hospital stay, and neonatal morbidity and mortality. The study was ended prematurely based on results of the intermediate analysis.
  
  
  RESULTS
  Preterm birth occurred in 42.5% of women in the progesterone group versus 35.5% in the placebo group (relative risk [RR] 1.2; 95% confidence interval [95% CI] 0.93-1.5). Delivery at <32 and <34 weeks did not differ between the two groups (12.9 versus 9.7%; [RR 1.3; 95% CI 0.7-2.5] and 19.7 versus 12.9% [RR 1.5; 95% CI 0.9-2.4], respectively). The duration of tocolysis, hospitalisation, and recurrence of preterm labour were comparable between groups. Neonatal morbidity occurred in 44 (22.8%) cases on progesterone versus 35 (18.8%) cases on placebo (RR: 1.2; 95% CI 0.82-1.8), whereas there were 4 (2%) neonatal deaths in each study group.
  
  
  CONCLUSIONS
  There is no evidence that the daily administration of 200 mg vaginal progesterone decreases preterm birth or improves neonatal outcome in women with preterm labour.
authors.affiliation: Department of Obstetrics and Gynaecology, Faculty of Medicine, Geneva University Hospitals and University of Geneva, Geneva, Switzerland.
authors.forename: B
authors.initials: B
authors.lastname: Martinez de Tejada
authors.forename: A
authors.initials: A
authors.lastname: Karolinski
authors.forename: M C
authors.initials: MC
authors.lastname: Ocampo
authors.forename: C
authors.initials: C
authors.lastname: Laterra
authors.forename: I
authors.initials: I
authors.lastname: Hösli
authors.forename: D
authors.initials: D
authors.lastname: Fernández
authors.forename: D
authors.initials: D
authors.lastname: Surbek
authors.forename: M
authors.initials: M
authors.lastname: Huespe
authors.forename: G
authors.initials: G
authors.lastname: Drack
authors.forename: A
authors.initials: A
authors.lastname: Bunader
authors.forename: S
authors.initials: S
authors.lastname: Rouillier
authors.forename: G
authors.initials: G
authors.lastname: López de Degani
authors.forename: E
authors.initials: E
authors.lastname: Seidenstein
authors.forename: E
authors.initials: E
authors.lastname: Prentl
authors.forename: J
authors.initials: J
authors.lastname: Antón
authors.forename: F
authors.initials: F
authors.lastname: Krähenmann
authors.forename: D
authors.initials: D
authors.lastname: Nowacki
authors.forename: M
authors.initials: M
authors.lastname: Poncelas
authors.forename: J C
authors.initials: JC
authors.lastname: Nassif
authors.forename: R
authors.initials: R
authors.lastname: Papera
authors.forename: C
authors.initials: C
authors.lastname: Tuma
authors.forename: R
authors.initials: R
authors.lastname: Espoile
authors.forename: O
authors.initials: O
authors.lastname: Tiberio
authors.forename: G
authors.initials: G
authors.lastname: Breccia
authors.forename: A
authors.initials: A
authors.lastname: Messina
authors.forename: B
authors.initials: B
authors.lastname: Peker
authors.forename: E
authors.initials: E
authors.lastname: Schinner
authors.forename: B W
authors.initials: BW
authors.lastname: Mol
authors.forename: L
authors.initials: L
authors.lastname: Kanterewicz
authors.forename: V
authors.initials: V
authors.lastname: Wainer
authors.forename: M
authors.initials: M
authors.lastname: Boulvain
authors.forename: V
authors.initials: V
authors.lastname: Othenin-Girard
authors.forename: M V
authors.initials: MV
authors.lastname: Bertolino
authors.forename: O
authors.initials: O
authors.lastname: Irion
mesh_terms: D000282:Administration, Intravaginal; D000328:Adult; D001034:Apgar Score; D001724:Birth Weight; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007213:Indomethacin / Q000627:therapeutic use; D007223:Infant; D007226:Infant Mortality; D007231:Infant, Newborn; D007363:Intensive Care Units, Neonatal / Q000706:statistics & numerical data; D007752:Obstetric Labor, Premature / Q000188:drug therapy*; D011247:Pregnancy; D011262:Pregnancy Trimester, Second; D011263:Pregnancy Trimester, Third; D047928:Premature Birth / Q000517:prevention & control*; D011374:Progesterone / Q000627:therapeutic use*; D011372:Progestins / Q000627:therapeutic use*; D018045:Receptors, Oxytocin / Q000037:antagonists & inhibitors; D015149:Tocolytic Agents / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D011372:Progestins; D018045:Receptors, Oxytocin; D015149:Tocolytic Agents; D011374:Progesterone; D007213:Indomethacin
keywords: Maternal tolerance; neonatal morbidity; neonatal mortality; neonatology; obstetrics; preterm delivery; preterm labour; vaginal progesterone