Vaginal progesterone for the prevention of preterm birth in twin gestations: a randomized placebo-controlled double-blind study

Brizot, Maria de Lourdes; Hernandez, Wagner Rodrigues; Liao, Adolfo Wenjaw; Bittar, Roberto Eduardo; Francisco, Rossana Pulcineli Vieira; Krebs, Vera Lúcia Jornada; Zugaib, Marcelo

doi:10.1016/j.ajog.2015.02.021

Cited by 63 publications

(96 citation statements)

References 18 publications

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“…The individual characteristics of the studies included in the meta-analysis are shown in Table 2. Five studies were double-blind, placebo-controlled trials [64][65][66][67][68] . The remaining study compared vaginal progesterone with no treatment 69 .…”

Section: Quality Of Evidencementioning

confidence: 99%

“…The remaining study compared vaginal progesterone with no treatment 69 . Three studies were performed in low/middle-income countries 65,68,69 , two in high-income countries 66,67 and one in both low/middle-and high-income countries 64 . Two trials were specifically designed to evaluate the use of vaginal progesterone in women with a twin gestation and a sonographic short cervix (CL ≤ 15 mm 64 and CL between 20 and 25 mm 69 ).…”

Section: Quality Of Evidencementioning

confidence: 99%

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Vaginal progesterone decreases preterm birth and neonatal morbidity and mortality in women with a twin gestation and a short cervix: an updated meta‐analysis of individual patient data

Romero

Conde-Agudelo

El-refaie

et al. 2017

Ultrasound in Obstet & Gyne

187

115

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ObjectiveTo assess the efficacy of vaginal progesterone for the prevention of preterm birth and neonatal morbidity and mortality in asymptomatic women with a twin gestation and a sonographic short cervix (cervical length ≤ 25 mm) in the mid‐trimester.MethodsThis was an updated systematic review and meta‐analysis of individual patient data (IPD) from randomized controlled trials comparing vaginal progesterone with placebo/no treatment in women with a twin gestation and a mid‐trimester sonographic cervical length ≤ 25 mm. MEDLINE, EMBASE, POPLINE, CINAHL and LILACS (all from inception to 31 December 2016), the Cochrane Central Register of Controlled Trials, Research Registers of ongoing trials, Google Scholar, conference proceedings and reference lists of identified studies were searched. The primary outcome measure was preterm birth < 33 weeks' gestation. 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.ResultsIPD were available for 303 women (159 assigned to vaginal progesterone and 144 assigned to placebo/no treatment) and their 606 fetuses/infants from six randomized controlled trials. One study, which included women with a cervical length between 20 and 25 mm, provided 74% of the total sample size of the IPD meta‐analysis. Vaginal progesterone, compared with placebo/no treatment, was associated with a statistically significant reduction in the risk of preterm birth < 33 weeks' gestation (31.4% vs 43.1%; RR, 0.69 (95% CI, 0.51–0.93); moderate‐quality evidence). Moreover, vaginal progesterone administration was associated with a significant decrease in the risk of preterm birth < 35, < 34, < 32 and < 30 weeks' gestation (RRs ranging from 0.47 to 0.83), neonatal death (RR, 0.53 (95% CI, 0.35–0.81)), respiratory distress syndrome (RR, 0.70 (95% CI, 0.56–0.89)), composite neonatal morbidity and mortality (RR, 0.61 (95% CI, 0.34–0.98)), use of mechanical ventilation (RR, 0.54 (95% CI, 0.36–0.81)) and birth weight < 1500 g (RR, 0.53 (95% CI, 0.35–0.80)) (all moderate‐quality evidence). There were no significant differences in neurodevelopmental outcomes at 4–5 years of age between the vaginal progesterone and placebo groups.ConclusionAdministration of vaginal progesterone to asymptomatic women with a twin gestation and a sonographic short cervix in the mid‐trimester reduces the risk of preterm birth occurring at < 30 to < 35 gestational weeks, neonatal mortality and some measures of neonatal morbidity, without any demonstrable deleterious effects on childhood neurodevelopment. Published 2017. This article is a U.S. Government work and is in the public domain in the USA. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

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Section: Quality Of Evidencementioning

confidence: 99%

Section: Quality Of Evidencementioning

confidence: 99%

Vaginal progesterone decreases preterm birth and neonatal morbidity and mortality in women with a twin gestation and a short cervix: an updated meta‐analysis of individual patient data

Romero

Conde-Agudelo

El-refaie

et al. 2017

Ultrasound in Obstet & Gyne

187

115

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“…Na przykład, u kobiet zagrożonych przedwczesnym porodem podjęto próbę dopochwowego zastosowania progesteronu w dawce dziennej 200 mg, co jednak nie przyniosło spodziewanego efektu (7,28,52). Wykazano natomiast, że podawanie progesteronu może być skuteczne w przypadku kobiet ze skróconą szyjką macicy (35,40).…”

Section: Rezultaty I Wnioskiunclassified

Methods of prolonging a pregnancy threatened with preterm labour

Dobrzynski¹,

Max²,

Jurka³

2016

Medycyna Weterynaryjna

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479 Artykuł przeglądowy ReviewWłaściwa, gatunkowo swoista długość ciąży warunkuje odpowiedni rozwój płodów, dojrzałość ło-żyska i fizjologiczny przebieg porodu oraz okresu poporodowego. Odchylenia poza wartości uznane za prawidłowe, zarówno w górę, jak i w dół, stanowią zagrożenie, zwłaszcza dla płodu, zmniejszając szansę jego przeżycia, szczególnie gdy dochodzi do porodu przedwczesnego. Z danych epidemiologicznych wynika, że u ludzi ponad 10% porodów odbywa się przedterminowo, a to oznacza, że rocznie blisko 15 milionów dzieci rodzi się jako wcześniaki, co bezpośrednio skutkuje śmiercią około 1 miliona spośród tych noworodków (3). Długość ciąży jest modulowana przy udziale czynników społecznych i środowiskowych, ale także podlega epigenetycznej regulacji aktywności genów. Stwierdzono na przykład, że zjawisko przedwczesnych porodów jest związane ze zmianami w metylacji DNA i w konsekwencji w ekspresji genów kodujących białka biorące udział w aktywności skurczowej macicy (31). Problemy z niefizjologiczną długością ciąży występują także u zwierząt, w tym psów i kotów. Uważa się, że u tych gatunków płody uzyskują dojrzałość w wieku 56-58 dni. Zatem za poród przedwczesny należy uznać ten, który rozpoczyna się przed tym terminem. Problemem praktycznym jest ustalenie aktualnego wieku płodów, zwłaszcza u psów, o ile wcześniej (w okresie krycia) nie przeprowadzano żadnych badań, które bezpośrednio lub pośrednio wskazywałyby termin owulacji. Jeżeli jest on znany, to przyjmuje się, że po kolejnych 2 dniach może dojść do zapłodnienia, gdy plemniki zostały zdeponowane wcześniej. O ile krycie/unasiennianie odbywa się później niż 2 dni po owulacji, to z początkiem ciąży można się liczyć od następnego dnia. Jeżeli natomiast termin owulacji nie jest znany, to istnieją możliwości określenia zaawansowania ciąży przy wykorzystaniu diagnostyki obrazowej -na podstawie ultrasonograficznego obrazowania struktur zarodkowo-płodowych pomiarów wewnętrznej średnicy jamy kosmówkowej lub podłużnych i poprzecznych pomiarów płodów (fe- Methods of prolonging a pregnancy threatened with preterm labour Summary Both prolonged and shortened pregnancies carry the risk of increased mortality of the offspring. The main causes of early delivery are genetic factors, bacterial and viral infections, corpus luteum insufficiency and pathologies of the placenta. Antepartum luteolysis is due to the activity of prostaglandin F2α. A decrease in the progesterone concentration activates the sensitivity of the uterine muscles to oxytocin. Calcium ions move into the myocytes and bind to calmodulin, starting enzymatic reactions necessary for muscle contraction. Oxytocin promotes prostaglandin F2α release. Cholesterol and magnesium stimulate the binding of oxytocin to its receptors. A premature delivery is caused by a disorder of the balance between contractility and relaxation of the myometrium, which is regulated by many signalling pathways. Birth in humans can be postponed by the use of many different tocolytic medications, β-adrenergic drugs (ritodrine, hexoprena...

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“…The mechanism of action suggested is downregulation of the expression of pro-inflammatory mediators such as iNOS and COX-2, and suppression of the produc-tion of eicosanoids such as prostaglandins. Although promise has been shown in murine models, clinical translation might not give the same results, as many human trials with progesterone have failed to curb PTB [28,61,62].…”

Section: Resveratrolmentioning

confidence: 99%

Preterm Birth: An Inflammatory Syndrome, Not Just A Myometrial Disorder

Mai-Vo¹,

Nadeau-Vallée²,

Beaudry-Richard³

2017

UOJM

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Preterm birth (PTB) is the leading cause of neonatal mortality and morbidity. Although the severity of neonatal outcomes is inversely correlated with gestational age, all PTBs can lead to potentially life-threatening neonatal outcomes and major lifelong health complications. Because advances in neonatal care have substantially decreased neonatal mortality, the incidence of PTB and its complications is unabatedly rising. PTB currently affects more than 10% of births worldwide, with similar numbers in developed countries. Correspondingly, improving neonatal outcome is a key objective of the World Health Organization. The recently approved (in Europe) tocolytics drug, Atosiban, used to prolong preterm gestation, has not been shown to improve neonatal outcome, nor have other tocolytic agents used in clinic. Thus, PTB remains an unmet medical need. Recent evidence shows that most, if not all, PTBs are associated with (overt or occult) inflammatory processes in gestational tissues, independent of infection. Proinflammatory cytokines are produced from maternal and fetal cells in response to sterile or infectious stressors. These seem to orchestrate a multi-tissue response including myometrial contractility, cervical ripening, and weakening/rupture of fetal membranes, leading to the onset of preterm labor. This integrated system might have been conserved through mammalian evolution due to increased maternal and/or fetal survival when gestation is terminated in specific settings, such as infection. Hence, inflammation may be a common pathway to the numerous aetiologies of PTB. Most importantly, recent evidence suggests that inflammation is transmitted to the fetus, thereby inducing organ injuries that may underlie the development of major neonatal diseases. Targeting inflammation prenatally instead of myometrial contraction could be a more successful and safe approach for the management of PTB, as suggested by recent animal studies. ABSTRACTLa naissance prématurée est la principale cause de mortalité et de morbidité néonatale. Bien que la sévérité des issus néonataux soit inversement corrélée avec l'âge gestationnel à la naissance, toutes les naissances prématurées peuvent mener à des issus néonataux potentiellement mortels et à des complications avec répercussions s'échelonnant sur toute la vie. Étant donné que la mortalité néonatale a considérablement diminuée avec les récentes avancées en néonatalogie, l'incidence de la naissance préma-turée et de ses complications sont en hausse. La naissance prématurée affecte présentement plus de 10% des naissances à travers le monde, avec des taux similaires dans les pays développés. Conséquemment, d'améliorer l'issu néonatal est un objectif clé de l'Organisation Mondiale de la Santé. Le tocolytique Atosiban récemment approuvé (en Europe) pour prolonger les gestations pré-maturées n'a pas démontré d'efficacité pour améliorer les issus néonataux, tout comme les autres tocolytiques utilisés en clinique, et la naissance prématurée demeure un besoin médical non-atteint. Des données r...

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Vaginal progesterone for the prevention of preterm birth in twin gestations: a randomized placebo-controlled double-blind study

Cited by 63 publications

References 18 publications

Vaginal progesterone decreases preterm birth and neonatal morbidity and mortality in women with a twin gestation and a short cervix: an updated meta‐analysis of individual patient data

Vaginal progesterone decreases preterm birth and neonatal morbidity and mortality in women with a twin gestation and a short cervix: an updated meta‐analysis of individual patient data

Methods of prolonging a pregnancy threatened with preterm labour

Preterm Birth: An Inflammatory Syndrome, Not Just A Myometrial Disorder

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