Prevention of preterm delivery with vaginal progesterone in women with preterm labour (4P): randomised double‐blind placebo‐controlled trial

Tejada, Begoña Martínez de; Karolinski, Ariel; Ocampo, MC; Laterra, Cristina; Hösli, Irène; Fernández, Douglas; Surbek, Daniel; Huespe, M; Drack, G.; Bunader, A.; Rouillier, S; Degani, G López de; Seidenstein, E; Prentl, Elke; Antón, José Ignacio; Krähenmann, Franziska; Nowacki, D; Poncelas, M; Nassif, JC; Papera, R; Tuma, Christopher W.; Espoile, R; Tiberio, O; Breccia, G; Messina, Analía; Peker, Berna Haliloglu; Schinner, E; Mol, BW; Kanterewicz, Luciana G.; Wainer, V.; Boulvain, Michel; Othenin‐Girard, Véronique; Bertolino, M; Irion, Olivier

doi:10.1111/1471-0528.13061

Cited by 60 publications

(64 citation statements)

References 68 publications

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“…The only well‐designed RCT with an adequate sample size, but without a placebo, using 500 mg 17P per week, and a small trial also using 17P, showed that this strategy did not prolong pregnancy. This was a similar conclusion to that of a recently‐published RCT using progesterone in women with preterm labour still on tocolysis . Regardless of these results, information about any potential benefit of vaginal progesterone after the preterm labour episode has been arrested and tocolysis is complete is lacking.…”

Section: Discussionsupporting

confidence: 79%

“…Earlier clinical trials using 17‐hydroxyprogesterone reported no apparent benefit on perinatal outcomes, whereas five small clinical trials using vaginal natural progesterone have reported prolongation of pregnancy . A recently published study failed to show the effectiveness of vaginal progesterone in preventing preterm birth after prolonged treatment in women with preterm labour, however …”

Section: Introductionmentioning

confidence: 99%

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Vaginal progesterone as maintenance treatment after an episode of preterm labour (PROMISE) study: a multicentre, double‐blind, randomised, placebo‐controlled trial

Palacio

Cobo

Antolín

et al. 2016

BJOG

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Objective To evaluate whether maintenance treatment with vaginal progesterone after an arrested preterm labour reduces the incidence of preterm delivery.Design Multicentre, randomised, double-blind, placebo-controlled trial.Setting Twelve tertiary care centres in Spain.Population A total of 265 women with singleton pregnancy, preterm labour successfully arrested with tocolytic treatment, and cervical length of <25 mm.Methods Randomisation was stratified by gestational age (from 24.0 to <31.0 weeks of gestation and from 31.0 to <34.0 weeks of gestation) and centre. Patients were randomly assigned, in a 1 : 1 ratio, to either daily vaginal capsules of 200 mg progesterone or placebo until delivery or 36.6 weeks of gestation, whichever occurred first.Main outcome measures Primary outcome was delivery before 34.0 and 37.0 weeks of gestation. Secondary outcomes were discharge-todelivery time, readmissions because of preterm labour, emergency service use, and neonatal morbidity and mortality.Results From June 2008 through June 2012, 1419 women were screened: 472 met the inclusion criteria and 265 were randomised. The final analysis included 258 women: 126 in the progesterone group and 132 in the placebo group. There were no significant differences between the progesterone and placebo groups in terms of delivery at <34 weeks of gestation [9/126 (7.1%) versus 10/132 (7.6%), P = 0.91] or <37 weeks of gestation [36/126 (28.6%) versus 29/132 (22.0%), P = 0.22]. There were no differences observed between groups when considering the two strata of gestational age at inclusion.Conclusions A maintenance treatment of 200 mg of daily vaginal progesterone capsules in women discharged home after an episode of arrested preterm labour did not significantly reduce the rate of preterm delivery.Keywords Maintenance treatment, preterm labour, progesterone.Tweetable abstract Maintenance progesterone in 258 women after arrested PTL showed no benefit. A, Scazzocchio E, Olivares JM, Varea S, R ıos J, Gratac os E on behalf of the PROMISE Collaborative Group. Vaginal progesterone as maintenance treatment after an episode of preterm labour (PROMISE) study: a multicentre, double-blind, randomised, placebo-controlled trial.

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Section: Discussionsupporting

confidence: 79%

Section: Introductionmentioning

confidence: 99%

Vaginal progesterone as maintenance treatment after an episode of preterm labour (PROMISE) study: a multicentre, double‐blind, randomised, placebo‐controlled trial

Palacio

Cobo

Antolín

et al. 2016

BJOG

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“…Because progesterone is safe and may be effective in some patients, many obstetricians use it as prophylaxis therapy to prevent PTB. However, the use of progesterone as an acute tocolytic was unsuccessful [29].…”

Section: Indomethacinmentioning

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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“…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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Prevention of preterm delivery with vaginal progesterone in women with preterm labour (4P): randomised double‐blind placebo‐controlled trial

Cited by 60 publications

References 68 publications

Vaginal progesterone as maintenance treatment after an episode of preterm labour (PROMISE) study: a multicentre, double‐blind, randomised, placebo‐controlled trial

Vaginal progesterone as maintenance treatment after an episode of preterm labour (PROMISE) study: a multicentre, double‐blind, randomised, placebo‐controlled trial

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

Methods of prolonging a pregnancy threatened with preterm labour

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