A Trial of 17 Alpha-Hydroxyprogesterone Caproate to Prevent Prematurity in Twins

Rouse, Dwight J.; Caritis, Steve N.; Peaceman, Alan M.; Sciscione, Anthony; Thom, Elizabeth; Spong, Catherine Y.; Varner, Michael W.; Malone, Fergal D.; Iams, Jay D.; Mercer, Brian M.; Thorp, John M.; Sorokin, Yoram; Carpenter, Marshall W.; Lo, Julie; Ramin, Susan M.; Harper, Margaret; Anderson, Garland

doi:10.1056/nejmoa070641

Cited by 339 publications

(204 citation statements)

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“…28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 Eighteen studies provided data on both monochorionic and dichorionic,16 30 32 34 36 38 40 42 43 44 45 48 49 50 51 54 56 57 seven on only monochorionic,29 31 37 39 41 47 53 and seven on only dichorionic twin pregnancies 2833 35 46 52 55 58 Twenty three authors provided relevant unpublished data 16…”

Section: Resultsmentioning

confidence: 99%

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Prospective risk of stillbirth and neonatal complications in twin pregnancies: systematic review and meta-analysis

Cheong-See

Schuit

Arroyo-Manzano

et al. 2016

BMJ

188

150

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Objective To determine the risks of stillbirth and neonatal complications by gestational age in uncomplicated monochorionic and dichorionic twin pregnancies.Design Systematic review and meta-analysis.Data sources Medline, Embase, and Cochrane databases (until December 2015). Review methods Databases were searched without language restrictions for studies of women with uncomplicated twin pregnancies that reported rates of stillbirth and neonatal outcomes at various gestational ages. Pregnancies with unclear chorionicity, monoamnionicity, and twin to twin transfusion syndrome were excluded. Meta-analyses of observational studies and cohorts nested within randomised studies were undertaken. Prospective risk of stillbirth was computed for each study at a given week of gestation and compared with the risk of neonatal death among deliveries in the same week. Gestational age specific differences in risk were estimated for stillbirths and neonatal deaths in monochorionic and dichorionic twin pregnancies after 34 weeks’ gestation.Results 32 studies (29 685 dichorionic, 5486 monochorionic pregnancies) were included. In dichorionic twin pregnancies beyond 34 weeks (15 studies, 17 830 pregnancies), the prospective weekly risk of stillbirths from expectant management and the risk of neonatal death from delivery were balanced at 37 weeks’ gestation (risk difference 1.2/1000, 95% confidence interval −1.3 to 3.6; I2=0%). Delay in delivery by a week (to 38 weeks) led to an additional 8.8 perinatal deaths per 1000 pregnancies (95% confidence interval 3.6 to 14.0/1000; I2=0%) compared with the previous week. In monochorionic pregnancies beyond 34 weeks (13 studies, 2149 pregnancies), there was a trend towards an increase in stillbirths compared with neonatal deaths after 36 weeks, with an additional 2.5 per 1000 perinatal deaths, which was not significant (−12.4 to 17.4/1000; I2=0%). The rates of neonatal morbidity showed a consistent reduction with increasing gestational age in monochorionic and dichorionic pregnancies, and admission to the neonatal intensive care unit was the commonest neonatal complication. The actual risk of stillbirth near term might be higher than reported estimates because of the policy of planned delivery in twin pregnancies.Conclusions To minimise perinatal deaths, in uncomplicated dichorionic twin pregnancies delivery should be considered at 37 weeks’ gestation; in monochorionic pregnancies delivery should be considered at 36 weeks.Systematic review registration PROSPERO CRD42014007538.

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Section: Resultsmentioning

confidence: 99%

“…33 35 46 52 55 58 Twenty three authors provided relevant unpublished data 1628 30 32 33 34 35 38 39 41 42 43 47 48 49 50 51 52 53 54 56 57 58…”

Section: Resultsmentioning

confidence: 99%

Prospective risk of stillbirth and neonatal complications in twin pregnancies: systematic review and meta-analysis

Cheong-See

Schuit

Arroyo-Manzano

et al. 2016

BMJ

188

150

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“…This in turn would suppress its production of DHEAS and ultimately reduce the placenta's production of estriol. Such a mechanism might explain the finding that 17OHPC failed to prevent preterm birth in twins, 27 in which the primary stimulus for labor may be uterine distention, 28 rather than fetal adrenal activity.…”

Section: Commentmentioning

confidence: 99%

Salivary progesterone and estriol among pregnant women treated with 17-α-hydroxyprogesterone caproate or placebo

Klebanoff

Meis

Dombrowski

et al. 2008

American Journal of Obstetrics and Gynecology

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OBJECTIVE-The objectives of the study was to determine whether salivary progesterone (P) or estriol (E3) concentration at 16-20 weeks' gestation predicts preterm birth or the response to 17α-hydroxyprogesterone caproate (17OHPC) and whether 17OHPC treatment affected the trajectory of salivary P and E3 as pregnancy progressed.STUDY DESIGN-This was a secondary analysis of a clinical trial of 17OHPC to prevent preterm birth. Baseline saliva was assayed for P and E3. Weekly salivary samples were obtained from 40 women who received 17OHPC and 40 who received placebo in a multicenter ran-domized trial of 17OHPC to prevent recurrent preterm delivery.RESULTS-Both low and high baseline saliva P and E3 were associated with a slightly increased risk of preterm birth. However, 17OHPC prevented preterm birth comparably, regardless of baseline salivary hormone concentrations. 17OHPC did not alter the trajectory of salivary P over pregnancy, but it significantly blunted the rise in salivary E3 as well as the rise in the E3/P ratio. NIH Public AccessAuthor Manuscript Am J Obstet Gynecol. Author manuscript; available in PMC 2009 December 16. Published in final edited form as: Am J Obstet Gynecol. 2008 November ; 199(5): 506.e1-506.e7. doi:10.1016/j.ajog.2008.003. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript CONCLUSION-17OHPC flattened the trajectory of E3 in the second half of pregnancy, suggesting that the drug influences the fetoplacental unit. Keywords17-alpha-hydroxyprogesterone caproate; longitudinal studies; preterm birth; salivary estriol; salivary progesterone Progesterone has long been recognized as necessary for pregnancy maintenance, and the role of progesterone withdrawal in the initiation of labor in animal species has been known for decades. 1 However, the role of progesterone withdrawal, as measured by plasma progesterone concentration or the ratio of progesterone/estrogens, in the initiation of normal labor in humans or other primates is unclear. 2-4 Nevertheless, there is evidence that functional progesterone withdrawal caused by changes such as reduction in progesterone receptors 5 or relative increase in the progesterone receptor (PR)-A progesterone receptor isoform, which blocks PR-B isoform-mediated gene transcription 6 may trigger labor in humans. We are unaware of any study that has assessed the ability of measurement of salivary progesterone, which is representative of the biologically active unbound fraction in plasma or serum, 7 to predict preterm birth.In 2 recent randomized clinical trials, injections of 17-α-hydroxyprogesteronecaproate (17OHPC) 8 or vaginal suppositories containing progesterone 9 reduced the recurrence or occurrence of preterm birth among high-risk women. Because 17-α-hydroxyprogesterone is produced by the normal placenta in amounts greater than the doses administered in these clinical trials 10 and because normal plasma progesterone concentrations are 9 times higher than those of 17-α-hydroxyprogesterone 11 and greater than the dissociation c...

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“…[10][11][12][13][14][15][16][17] • Progestational agents such as 17α-hydroxy-progesterone caproate reduce recurrent preterm birth in some women with a prior preterm birth, 18,19 especially those with early preterm birth 20 and short cervix, 21 but have no effect on preterm birth in multiple gestations. 22,23 NIH Public Access …”

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confidence: 99%

“…The indication for 17P in this instance is an obstetrical history of spontaneous preterm birth, but 17P is not effective in women with multifetal pregnancy. 22,23 We recommend that this decision be individualized after a detailed history of the prior preterm birth.○ Should progesterone supplementation be used in women with a prior spontaneous preterm birth of a twin pregnancy? There are no clinical trial data to guide this decision in women with this combination of historical and current risk factors.…”

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Care for Women with Prior Preterm Birth

Iams

2010

Preterm Birth

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Women who have delivered an infant between 16 and 36 weeks' gestation have an increased risk of preterm birth in subsequent pregnancies. The risk increases with more than 1 preterm birth and is inversely proportional to the gestational age of the previous preterm birth. African American women have rates of recurrent preterm birth that are nearly twice that of women of other backgrounds. An approximate risk of recurrent preterm birth can be estimated by a comprehensive reproductive history, with emphasis on maternal race, the number and gestational age of prior births, and the sequence of events preceding the index preterm birth. Interventions including smoking cessation, eradication of asymptomatic bacteriuria, progestational agents, and cervical cerclage can reduce the risk of recurrent preterm birth when employed appropriately. Keywordscerclage; prevention; progesterone; recurrent; preterm birth; risk estimation Efforts to reduce the incidence of preterm birth cannot yet be called successful but have produced sufficient information to justify management suggestions for clinicians, not only for strategies that do not work but also for those that do. The quality and number of clinical trials of interventions intended to reduce the incidence and/or morbidity of preterm birth has risen substantially in recent years, yielding data that can improve care for women at risk.An important advance has been the revision of the traditional model of preterm birth in which painful contractions or preterm membrane rupture were understood as the most common initial steps preceding cervical change. This concept has been challenged by observations from several clinical studies:• Drugs that arrest or inhibit uterine contractions can delay delivery but do not reliably reduce or prevent preterm birth. [1][2][3][4][5] • Assessment of contraction frequency is not a useful test to predict preterm birth, 6 and its use to detect and arrest initial or recurrent episodes of preterm labor does not affect the rate of preterm birth. [7][8][9] • Antibiotics that eradicate microorganisms associated with preterm birth also do not reliably reduce, and may sometimes increase, the incidence of preterm birth, especially in women with intact membranes. [10][11][12][13][14][15][16][17] • Progestational agents such as 17α-hydroxy-progesterone caproate reduce recurrent preterm birth in some women with a prior preterm birth, 18,19 especially those with early preterm birth 20 and short cervix, 21 but have no effect on preterm birth in multiple gestations. 22,23 NIH Public Access Author ManuscriptAm J Obstet Gynecol. Author manuscript; available in PMC 2013 May 09. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript• Cervical cerclage can reduce recurrent preterm birth in women with a prior preterm birth and short cervix 24,25 but increases the risk of preterm birth in women with multiple gestation who also have a short cervix. 24 These findings suggest the following 4 substantive changes in the "contractions change the cervi...

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A Trial of 17 Alpha-Hydroxyprogesterone Caproate to Prevent Prematurity in Twins

Abstract: Treatment with 17 alpha-hydroxyprogesterone caproate did not reduce the rate of preterm birth in women with twin gestations. (ClinicalTrials.gov number, NCT00099164 [ClinicalTrials.gov].).

Cited by 339 publications

References 11 publications

Prospective risk of stillbirth and neonatal complications in twin pregnancies: systematic review and meta-analysis

Prospective risk of stillbirth and neonatal complications in twin pregnancies: systematic review and meta-analysis

Salivary progesterone and estriol among pregnant women treated with 17-α-hydroxyprogesterone caproate or placebo

Care for Women with Prior Preterm Birth

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