Progestogens to prevent preterm birth in twin pregnancies: an individual participant data meta-analysis of randomized trials

Ewoud Schuit, Sarah Stock, Rolf H H Groenwold, Kimberly Maurel, C Andrew Combs, Thomas Garite, Cathy Y Spong, Elizabeth A Thom, Dwight J Rouse, Steve N Caritis, George R Saade, Julia M Zachary, Jane E Norman, Line Rode, Katharina Klein, Ann Tabor, Elçin Cetingöz, John C Morrison, Everett F Magann, Christian M Briery, Vicente Serra, Alfredo Perales, Juan Meseguer, Anwar H Nassar, Arianne C Lim, Karel G M Moons, Anneke Kwee, Ben Willem J Mol, Ewoud Schuit, Sarah Stock, Rolf H H Groenwold, Kimberly Maurel, C Andrew Combs, Thomas Garite, Cathy Y Spong, Elizabeth A Thom, Dwight J Rouse, Steve N Caritis, George R Saade, Julia M Zachary, Jane E Norman, Line Rode, Katharina Klein, Ann Tabor, Elçin Cetingöz, John C Morrison, Everett F Magann, Christian M Briery, Vicente Serra, Alfredo Perales, Juan Meseguer, Anwar H Nassar, Arianne C Lim, Karel G M Moons, Anneke Kwee, Ben Willem J Mol

Abstract

Background: Preterm birth is the principal factor contributing to adverse outcomes in multiple pregnancies. Randomized controlled trials of progestogens to prevent preterm birth in twin pregnancies have shown no clear benefits. However, individual studies have not had sufficient power to evaluate potential benefits in women at particular high risk of early delivery (for example, women with a previous preterm birth or short cervix) or to determine adverse effects for rare outcomes such as intrauterine death.

Methods/design: We propose an individual participant data meta-analysis of high quality randomized, double-blind, placebo-controlled trials of progestogen treatment in women with a twin pregnancy. The primary outcome will be adverse perinatal outcome (a composite measure of perinatal mortality and significant neonatal morbidity). Missing data will be imputed within each original study, before data of the individual studies are pooled. The effects of 17-hydroxyprogesterone caproate or vaginal progesterone treatment in women with twin pregnancies will be estimated by means of a random effects log-binomial model. Analyses will be adjusted for variables used in stratified randomization as appropriate. Pre-specified subgroup analysis will be performed to explore the effect of progestogen treatment in high-risk groups.

Discussion: Combining individual patient data from different randomized trials has potential to provide valuable, clinically useful information regarding the benefits and potential harms of progestogens in women with twin pregnancy overall and in relevant subgroups.

References

    1. Scottish Perinatal and Infant Mortality and Morbidity Report, 2007. Edinburgh, Information Services Division, NHS Scotland; 2008. Ref Type: Report.
    1. Schaaf JM, Mol BW, bu-Hanna A, Ravelli AC. Trends in preterm birth: singleton and multiple pregnancies in the Netherlands, 2000-2007. BJOG. 2011;118:1196–1204. doi: 10.1111/j.1471-0528.2011.03010.x.
    1. Chauhan SP, Scardo JA, Hayes E, Abuhamad AZ, Berghella V. Twins: prevalence, problems, and preterm births. Am J Obstet Gynecol. 2010;203:305–315. doi: 10.1016/j.ajog.2010.04.031.
    1. da Fonseca EB, Bittar RE, Carvalho MH, Zugaib M. Prophylactic administration of progesterone by vaginal suppository to reduce the incidence of spontaneous preterm birth in women at increased risk: a randomized placebo-controlled double-blind study. Am J Obstet Gynecol. 2003;188:419–424. doi: 10.1067/mob.2003.41.
    1. Meis PJ, Klebanoff M, Thom E, Dombrowski MP, Sibai B, Moawad AH. et al.Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone caproate. N Engl J Med. 2003;348:2379–2385. doi: 10.1056/NEJMoa035140.
    1. Fonseca EB, Celik E, Parra M, Singh M, Nicolaides KH. Progesterone and the risk of preterm birth among women with a short cervix. N Engl J Med. 2007;357:462–469. doi: 10.1056/NEJMoa067815.
    1. Combs CA, Garite T, Maurel K, Das A, Porto M. 17-hydroxyprogesterone caproate for twin pregnancy: a double-blind, randomized clinical trial. Am J Obstet Gynecol. 2011;204:221–228.
    1. Rouse DJ, Caritis SN, Peaceman AM, Sciscione A, Thom EA, Spong CY. et al.A trial of 17 alpha-hydroxyprogesterone caproate to prevent prematurity in twins. N Engl J Med. 2007;357:454–461. doi: 10.1056/NEJMoa070641.
    1. Norman JE, Mackenzie F, Owen P, Mactier H, Hanretty K, Cooper S. et al.Progesterone for the prevention of preterm birth in twin pregnancy (STOPPIT): a randomised, double-blind, placebo-controlled study and meta-analysis. Lancet. 2009;373:2034–2040. doi: 10.1016/S0140-6736(09)60947-8.
    1. Cetingoz E, Cam C, Sakalli M, Karateke A, Celik C, Sancak A. Progesterone effects on preterm birth in high-risk pregnancies: a randomized placebo-controlled trial. Arch Gynecol Obstet. 2011;283:423–429. doi: 10.1007/s00404-009-1351-2.
    1. Briery CM, Veillon EW, Klauser CK, Martin RW, Chauhan SP, Magann EF. et al.Progesterone does not prevent preterm births in women with twins. South Med J. 2009;102:900–904. doi: 10.1097/SMJ.0b013e3181afee12.
    1. Lim AC, Schuit E, Bloemenkamp KW, Bernardus RE, Duvenkot JJ, Erwich JJ, 17-alpha hydroxyprogesterone caproate for the prevention of adverse neonatal outcome in multiple pregnancies: a randomised controlled trial. Obstet Gynecol. 2011. in press .
    1. Nassar AH, Usta IM. Prevention of Preterm Delivery in Twin Pregnancies by 17 Alpha-hydroxyprogesterone Caproate. ClinicalTrials gov Identifier: NCT00141908. 2006.
    1. Rode L, Tabor A. Does Progesterone Prevent Very Preterm Delivery in Twin Pregnancies? ClinicalTrials gov Identifier: NCT00329914. 2010.
    1. Rozenberg P. Efficacy of 17 Alpha-Hydroxyprogesterones Caproate for the Prevention of Preterm Delivery. ClinicalTrials gov Identifier:NCT00331695. 2006.
    1. Serra VS. Natural progesterone and preterm birth in twins. ClinicalTrials gov Identifier: NCT00480402. 2007.
    1. Riley RD, Lambert PC, bo-Zaid G. Meta-analysis of individual participant data: rationale, conduct, and reporting. BMJ. 2010;340:c221. doi: 10.1136/bmj.c221.
    1. Simmonds MC, Higgins JP, Stewart LA, Tierney JF, Clarke MJ, Thompson SG. Meta-analysis of individual patient data from randomized trials: a review of methods used in practice. Clin Trials. 2005;2:209–217. doi: 10.1191/1740774505cn087oa.
    1. Thompson SG, Higgins JP. Treating individuals 4: can meta-analysis help target interventions at individuals most likely to benefit? Lancet. 2005;365:341–346.
    1. Clarke MJ. Individual patient data meta-analyses. Best Pract Res Clin Obstet Gynaecol. 2005;19:47–55. doi: 10.1016/j.bpobgyn.2004.10.011.
    1. Caritis SN, Rouse DJ, Peaceman AM, Sciscione A, Momirova V, Spong CY. et al.Prevention of preterm birth in triplets using 17 alpha-hydroxyprogesterone caproate: a randomized controlled trial. Obstet Gynecol. 2009;113:285–292.
    1. Combs CA, Garite T, Maurel K, Das A, Porto M. Failure of 17-hydroxyprogesterone to reduce neonatal morbidity or prolong triplet pregnancy: a double-blind, randomized clinical trial. Am J Obstet Gynecol. 2010;203:248–249.
    1. Higgins JP, Green S. Cochrane Handbook for Systematic Reviews of Interventions. The Cochrane Collaboration; 2011.
    1. Donders AR, van der Heijden GJ, Stijnen T, Moons KG. Review: a gentle introduction to imputation of missing values. J Clin Epidemiol. 2006;59:1087–1091. doi: 10.1016/j.jclinepi.2006.01.014.
    1. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327:557–560. doi: 10.1136/bmj.327.7414.557.
    1. Carlin JB, Gurrin LC, Sterne JA, Morley R, Dwyer T. Regression models for twin studies: a critical review. Int J Epidemiol. 2005;34:1089–1099. doi: 10.1093/ije/dyi153.
    1. Smith CT, Williamson PR, Marson AG. Investigating heterogeneity in an individual patient data meta-analysis of time to event outcomes. Stat Med. 2005;24:1307–1319. doi: 10.1002/sim.2050.

Source: PubMed

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