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Vaginal progesterone prophylaxis for preterm birth (the OPPTIMUM study): a multicentre, randomised, double-blind trial

Lookup NU author(s): Professor Steve RobsonORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Background Progesterone administration has been shown to reduce the risk of preterm birth and neonatal morbidity in women at high risk, but there is uncertainty about longer term effects on the child.Methods We did a double-blind, randomised, placebo-controlled trial of vaginal progesterone, 200 mg daily taken from 22-24 to 34 weeks of gestation, on pregnancy and infant outcomes in women at risk of preterm birth (because of previous spontaneous birth at <= 34 weeks and 0 days of gestation, or a cervical length <= 25 mm, or because of a positive fetal fibronectin test combined with other clinical risk factors for preterm birth [any one of a history in a previous pregnancy of preterm birth, second trimester loss, preterm premature fetal membrane rupture, or a history of a cervical procedure to treat abnormal smears]). The objective of the study was to determine whether vaginal progesterone prophylaxis given to reduce the risk of preterm birth affects neonatal and childhood outcomes. We defined three primary outcomes: fetal death or birth before 34 weeks and 0 days gestation (obstetric), a composite of death, brain injury, or bronchopulmonary dysplasia (neonatal), and a standardised cognitive score at 2 years of age (childhood), imputing values for deaths. Randomisation was done through a web portal, with participants, investigators, and others involved in giving the intervention, assessing outcomes, or analysing data masked to treatment allocation until the end of the study. Analysis was by intention to treat. This trial is registered at ISRCTN. com, number ISRCTN14568373.Findings Between Feb 2, 2009, and April 12, 2013, we randomly assigned 1228 women to the placebo group (n=610) and the progesterone group (n=618). In the placebo group, data from 597, 587, and 439 women or babies were available for analysis of obstetric, neonatal, and childhood outcomes, respectively; in the progesterone group the corresponding numbers were 600, 589, and 430. After correction for multiple outcomes, progesterone had no significant effect on the primary obstetric outcome (odds ratio adjusted for multiple comparisons [OR] 0.86, 95% CI 0.61-1.22) or neonatal outcome (OR 0.62, 0.38-1.03), nor on the childhood outcome (cognitive score, progesterone group vs placebo group, 97.3 [SD 17.9] vs 97.7 [17.5]; difference in means -0.48, 95% CI -2.77 to 1.81). Maternal or child serious adverse events were reported in 70 (11%) of 610 patients in the placebo group and 59 (10%) of 616 patients in the progesterone group (p=0.27).Interpretation Vaginal progesterone was not associated with reduced risk of preterm birth or composite neonatal adverse outcomes, and had no long-term benefit or harm on outcomes in children at 2 years of age. Copyright (C) Norman et al. Open Access article distributed under the terms of CC BY.

Publication metadata

Author(s): Norman JE, Marlow N, Messow CM, Shennan A, Bennett PR, Thornton S, Robson SC, McConnachie A, Petrou S, Sebire NJ, Lavender T, Whyte S, Norrie J, OPPTIMUM Study Grp

Publication type: Article

Publication status: Published

Journal: Lancet

Year: 2016

Volume: 387

Issue: 10033

Pages: 2106-2116

Print publication date: 21/05/2016

Online publication date: 24/02/2016

Acceptance date: 01/01/1900

Date deposited: 26/07/2016

ISSN (print): 0140-6736

ISSN (electronic): 1474-547X

Publisher: Elsevier Science


DOI: 10.1016/S0140-6736(16)00350-0


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Funder referenceFunder name
Chief Scientist Office in Scotland
National Institute for Social Care and Research in Wales
Efficacy and Mechanism Evaluation (EME) Programme, a Medical Research Council (MRC)
09/800/27National Institute for Health Research (NIHR) partnership
G0700452National Institute for Health Research (NIHR) partnership