17-Hydroxyprogesterone caproate in triplet pregnancy: an individual patient data meta-analysis

C A Combs; E Schuit; S N Caritis; A C Lim; T J Garite; K Maurel; D Rouse; E Thom; A T Tita; Bwj Mol; Global Obstetrics Network (GONet) collaboration

doi:10.1111/1471-0528.13779

17-Hydroxyprogesterone caproate in triplet pregnancy: an individual patient data meta-analysis

BJOG. 2016 Apr;123(5):682-90. doi: 10.1111/1471-0528.13779. Epub 2015 Dec 10.

Authors

C A Combs¹, E Schuit^{2

3}, S N Caritis⁴, A C Lim⁵, T J Garite^{1

6}, K Maurel¹, D Rouse^{7

8

9}, E Thom^{7

10}, A T Tita^{8

11}, Bwj Mol^{5

12}; Global Obstetrics Network (GONet) collaboration

Affiliations

¹ Obstetrix Collaborative Research Network, the Center for Research, Education, and Quality, Mednax National Medical Group, Sunrise, FL, USA.
² Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht, the Netherlands.
³ Stanford Prevention Research Center, Stanford University, Stanford, CA, USA.
⁴ Department of Obstetrics and Gynecology, University of Pittsburgh, Pittsburgh, PA, USA.
⁵ Department of Obstetrics and Gynaecology, Academic Medical Centre Amsterdam, Amsterdam, the Netherlands.
⁶ Department of Obstetrics and Gynecology, University of California Irvine, Irvine, CA, USA.
⁷ The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Maternal-Fetal Medicine Units Network (MFMU), Bethesda, MD, USA.
⁸ Department of Obstetrics and Gynecology, Alpert Medical School, Women & Infants Hospital, Brown University, Providence, RI, USA.
⁹ Department of Epidemiology, School of Public Health, Brown University, Providence, RI, USA.
¹⁰ The Biostatistics Center, George Washington University, Washington, DC, USA.
¹¹ Department of Obstetrics and Gynecology and Center for Women's Reproductive Health, University of Alabama at Birmingham, Birmingham, AL, USA.
¹² The Robinson Research Institute, School of Paediatrics and Reproductive Health, University of Adelaide, and The South Australian Health and Medical Research Institute, Adelaide, SA, Australia.

Abstract

Background: Preterm birth complicates almost all triplet pregnancies and no preventive strategy has proven effective.

Objective: To determine, using individual patient data (IPD) meta-analysis, whether the outcome of triplet pregnancy is affected by prophylactic administration of 17-hydroxyprogesterone caproate (17OHPc).

Search strategy: We searched literature databases, trial registries and references in published articles.

Selection criteria: Randomised controlled trials (RCTs) of progestogens versus control that included women with triplet pregnancies.

Data collection and analysis: Investigators from identified RCTs collaborated on the protocol and contributed their IPD. The primary outcome was a composite measure of adverse perinatal outcome. The secondary outcome was the rate of birth before 32 weeks of gestation. Other pre-specified outcomes included randomisation-to-delivery interval and rates of birth at <24, <28 and <34 weeks of gestation.

Main results: Three RCTs of 17OHPc versus placebo included 232 mothers with triplet pregnancies and their 696 offspring. Risk-of-bias scores and between-study heterogeneity were low. Baseline characteristics were comparable between 17OHPc and placebo groups. The rate of the composite adverse perinatal outcome was similar among those treated with 17OHPc and those treated with placebo (34 and 35%, respectively; risk ratio [RR] 0.98, 95% confidence interval [95% CI] 0.79-1.2). The rate of birth at <32 weeks was also similar in the two groups (35 and 38%, respectively; RR 0.92, 95% CI 0.55-1.56). There were no significant between-group differences in perinatal mortality rate, randomisation-to-delivery interval, or other specified outcomes.

Conclusion: Prophylactic 17OHPc given to mothers with triplet pregnancies had no significant impact on perinatal outcome or pregnancy duration.

Tweetable abstract: 17-Hydroxyprogesterone caproate had no significant impact on the outcome or duration of triplet pregnancy.

Keywords: 17-Hydroxyprogesterone caproate; multiple gestation; preterm birth prevention; progestogens; triplet pregnancy.

Publication types

Meta-Analysis
Review

MeSH terms

17 alpha-Hydroxyprogesterone Caproate
Female
Humans
Hydroxyprogesterones / therapeutic use*
Pregnancy
Pregnancy, Triplet*
Premature Birth / prevention & control*
Progestins / therapeutic use*
Treatment Outcome

Substances

Hydroxyprogesterones
Progestins
17 alpha-Hydroxyprogesterone Caproate

Grants and funding

U01 HD036801/HD/NICHD NIH HHS/United States