title: Vaginal progesterone decreases preterm birth ≤ 34 weeks of gestation in women with a singleton pregnancy and a short cervix: an updated meta-analysis including data from the OPPTIMUM study.
abstract: OBJECTIVE
  To evaluate the efficacy of vaginal progesterone administration for preventing preterm birth and perinatal morbidity and mortality in asymptomatic women with a singleton gestation and a mid-trimester sonographic cervical length (CL) ≤ 25 mm.
  
  
  METHODS
  This was an updated systematic review and meta-analysis of randomized controlled trials comparing the use of vaginal progesterone to placebo/no treatment in women with a singleton gestation and a mid-trimester sonographic CL ≤ 25 mm. Electronic databases, from their inception to May 2016, bibliographies and conference proceedings were searched. The primary outcome measure was preterm birth ≤ 34 weeks of gestation or fetal death. Two reviewers independently selected studies, assessed the risk of bias and extracted the data. Pooled relative risks (RRs) with 95% confidence intervals (CI) were calculated.
  
  
  RESULTS
  Five trials involving 974 women were included. A meta-analysis, including data from the OPPTIMUM study, showed that vaginal progesterone significantly decreased the risk of preterm birth ≤ 34 weeks of gestation or fetal death compared to placebo (18.1% vs 27.5%; RR, 0.66 (95% CI, 0.52-0.83); P = 0.0005; five studies; 974 women). Meta-analyses of data from four trials (723 women) showed that vaginal progesterone administration was associated with a statistically significant reduction in the risk of preterm birth occurring at < 28 to < 36 gestational weeks (RRs from 0.51 to 0.79), respiratory distress syndrome (RR, 0.47 (95% CI, 0.27-0.81)), composite neonatal morbidity and mortality (RR, 0.59 (95% CI, 0.38-0.91)), birth weight < 1500 g (RR, 0.52 (95% CI, 0.34-0.81)) and admission to the neonatal intensive care unit (RR, 0.67 (95% CI, 0.50-0.91)). There were no significant differences in neurodevelopmental outcomes at 2 years of age between the vaginal progesterone and placebo groups.
  
  
  CONCLUSIONS
  This updated systematic review and meta-analysis reaffirms that vaginal progesterone reduces the risk of preterm birth and neonatal morbidity and mortality in women with a singleton gestation and a mid-trimester CL ≤ 25 mm, without any deleterious effects on neurodevelopmental outcome. Clinicians should continue to perform universal transvaginal CL screening at 18-24 weeks of gestation in women with a singleton gestation and to offer vaginal progesterone to those with a CL ≤ 25 mm. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.
authors.affiliation: Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Bethesda, MD and Detroit, MI, USA. romeror@mail.nih.gov.|Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI, USA. romeror@mail.nih.gov.|Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, MI, USA. romeror@mail.nih.gov.|Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI, USA. romeror@mail.nih.gov.
authors.forename: R
authors.initials: R
authors.lastname: Romero
authors.affiliation: Harris Birthright Research Centre for Fetal Medicine, King's College Hospital, London, UK.
authors.forename: K H
authors.initials: KH
authors.lastname: Nicolaides
authors.affiliation: Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Bethesda, MD and Detroit, MI, USA.
authors.forename: A
authors.initials: A
authors.lastname: Conde-Agudelo
authors.affiliation: Department of Obstetrics and Gynecology, University of Kentucky, Lexington, KY, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: O'Brien
authors.affiliation: Department of Obstetrics and Gynecology, Zeynep Kamil Women and Children Diseases Education and Research Hospital, Uskudar, Istanbul, Turkey.
authors.forename: E
authors.initials: E
authors.lastname: Cetingoz
authors.affiliation: Departamento de Obstetrícia e Ginecologia, Hospital do Servidor Publico Estadual 'Francisco Morato de Oliveira' and School of Medicine, University of São Paulo, São Paulo, Brazil.
authors.forename: E
authors.initials: E
authors.lastname: Da Fonseca
authors.affiliation: Center for Biomedical Research, Population Council, New York, NY, USA.
authors.forename: G W
authors.initials: GW
authors.lastname: Creasy
authors.affiliation: Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Bethesda, MD and Detroit, MI, USA.|Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA.
authors.forename: S S
authors.initials: SS
authors.lastname: Hassan
mesh_terms: D000282:Administration, Intravaginal; D054791:Cervical Length Measurement; D002584:Cervix Uteri / Q000187:drug effects* / Q000473:pathology; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D011247:Pregnancy; D047928:Premature Birth / Q000517:prevention & control*; D011374:Progesterone / Q000008:administration & dosage*; D011372:Progestins / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D011372:Progestins; D011374:Progesterone
keywords: cervical length; neonatal morbidity; neonatal mortality; prematurity; preterm delivery; progestins; progestogens; transvaginal ultrasound