Progesterone for the prevention of preterm birth in twin pregnancy (STOPPIT): a randomised, double-blind, placebo-controlled study and meta-analysis.
ABSTRACT Women with twin pregnancy are at high risk for spontaneous preterm delivery. Progesterone seems to be effective in reducing preterm birth in selected high-risk singleton pregnancies, albeit with no significant reduction in perinatal mortality and little evidence of neonatal benefit. We investigated the use of progesterone for prevention of preterm birth in twin pregnancy.
In this double-blind, placebo-controlled trial, 500 women with twin pregnancy were recruited from nine UK National Health Service clinics specialising in the management of twin pregnancy. Women were randomised, by permuted blocks of randomly mixed sizes, either to daily vaginal progesterone gel 90 mg (n=250) or to placebo gel (n=250) for 10 weeks from 24 weeks' gestation. All study personnel and participants were masked to treatment assignment for the duration of the study. The primary outcome was delivery or intrauterine death before 34 weeks' gestation. Analysis was by intention to treat. Additionally we undertook a meta-analysis of published and unpublished data to establish the efficacy of progesterone in prevention of early (<34 weeks' gestation) preterm birth or intrauterine death in women with twin pregnancy. This study is registered, number ISRCTN35782581.
Three participants in each group were lost to follow-up, leaving 247 analysed per group. The combined proportion of intrauterine death or delivery before 34 weeks of pregnancy was 24.7% (61/247) in the progesterone group and 19.4% (48/247) in the placebo group (odds ratio [OR] 1.36, 95% CI 0.89-2.09; p=0.16). The rate of adverse events did not differ between the two groups. The meta-analysis confirmed that progesterone does not prevent early preterm birth in women with twin pregnancy (pooled OR 1.16, 95% CI 0.89-1.51).
Progesterone, administered vaginally, does not prevent preterm birth in women with twin pregnancy.
Chief Scientist Office of the Scottish Government Health Directorate.
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ABSTRACT: It has been suggested that the quality of clinical trials should be assessed by blinded raters to limit the risk of introducing bias into meta-analyses and systematic reviews, and into the peer-review process. There is very little evidence in the literature to substantiate this. This study describes the development of an instrument to assess the quality of reports of randomized clinical trials (RCTs) in pain research and its use to determine the effect of rater blinding on the assessments of quality. A multidisciplinary panel of six judges produced an initial version of the instrument. Fourteen raters from three different backgrounds assessed the quality of 36 research reports in pain research, selected from three different samples. Seven were allocated randomly to perform the assessments under blind conditions. The final version of the instrument included three items. These items were scored consistently by all the raters regardless of background and could discriminate between reports from the different samples. Blind assessments produced significantly lower and more consistent scores than open assessments. The implications of this finding for systematic reviews, meta-analytic research and the peer-review process are discussed.Controlled Clinical Trials 03/1996; 17(1):1-12.
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ABSTRACT: We performed a systematic review to assess the benefits and harms of progesterone administration for the prevention of preterm birth in women and their infants. The Cochrane Controlled Trials Register was searched, and reference lists of retrieved studies were searched by hand. No date or language restrictions were placed. Randomized trials comparing antenatal progesterone for women at risk of preterm birth were considered. Studies were evaluated for inclusion and methodological quality. Primary outcomes were perinatal death, preterm birth before 34 weeks, and neurodevelopmental handicap. Eleven randomized controlled trials (2,425 women and 3,187 infants) were included. For women with a history of spontaneous preterm birth, progesterone was associated with a significant reduction in preterm birth before 34 weeks (one study, 142 women, RR 0.15, 95% CI 0.04-0.64, number needed to treat 7, 95% CI 4-17), but no statistically significant differences were identified for the outcome of perinatal death. For women with a short cervix identified on ultrasound, progesterone was not associated with a significant difference in perinatal death (one study, 274 participants, RR 0.38, 95% CI 0.10-1.40), but there was a significant reduction in preterm birth before 34 weeks (one study, 250 women, RR 0.58, 95% CI 0.38-0.87, number needed to treat 7, 95% CI 4-25). For women with a multiple pregnancy, progesterone was associated with no significant difference in perinatal death (one study, 154 participants, RR 1.95, 95% CI 0.37-10.33). For women presenting after threatened preterm labor, no primary outcomes were reported. For women with "other" risk factors for preterm birth, progesterone was not associated with a significant difference in perinatal death (two studies, 264 participants, RR 1.10, 95% CI 0.23-5.29). Progesterone is associated with some beneficial effects in pregnancy outcome for some women at increased risk of preterm birth.Obstetrics and Gynecology 08/2008; 112(1):127-34. · 4.80 Impact Factor
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ABSTRACT: The aim of this study is to assess the role of progesterone in preterm birth prevention. A MEDLINE search (from 1966 to the present; date of last search January 2005) was performed - using the key words progesterone, pregnancy, preterm birth, preterm labor, and randomized, controlled trial - in order to identify randomized, controlled trials in which progesterone (either intramuscular or vaginal administration) was compared with placebo or no treatment. Data were extracted and a meta-analysis was performed. Seven randomized, controlled trials were identified. Women who received progesterone were statistically significantly less likely to give birth before 37 weeks (seven studies, 1020 women, RR = 0.58, 95% CI = 0.48-0.70), to have an infant with birth weight of < or =2.5 kg (six studies, 872 infants, RR = 0.62, 95% CI = 0.49-0.78), or to have an infant diagnosed with intraventricular hemorrhage (one study, 458 infants, RR = 0.25, 95% CI = 0.08-0.82). For progesterone supplementation to be advocated for women at the risk of preterm birth, the prolongation of gestation demonstrated in this meta-analysis must translate into improved infant outcomes, including a reduction in mortality. There is currently insufficient information to allow recommendations regarding the optimal dose, route, and timing of administration of progesterone supplementation.Acta Obstetricia Et Gynecologica Scandinavica 06/2005; 84(6):526-33. · 1.85 Impact Factor