Professional Abstract
Objective
To evaluate the effectiveness of progestogens versus placebo or no intervention in reducing preterm birth (PTB) and associated maternal and neonatal complications
Study Design
| Design Element |
Description |
| Design |
IPD meta-analysis |
| Population |
5,598 women with a singleton pregnancy at risk for PTB mostly due to prior PTB or short cervix; 4,338 women with multifetal pregnancy, mostly with no other risk factors |
Interventions/
Comparators |
- Injectable 17-OHPC (a synthetic hormone) versus placebo or no intervention
- Vaginal progesterone (a natural hormone) versus placebo or no intervention
- Oral progesterone (a natural hormone) versus placebo or no intervention
- Injectable 17-OHPC versus vaginal progesterone
|
| Outcomes |
PTB before 28, 34, and 37 weeks; perinatal death; serious neonatal complications; maternal complications |
| Timeframe |
Not applicable |
This individual participant data (IPD) meta-analysis compared the effectiveness of progestogens versus placebo or no intervention in reducing PTB and associated neonatal and maternal complications.
Researchers searched bibliographic databases and international registries for published and unpublished randomized controlled trials completed prior to July 2016. They invited trial investigators to join a collaborative group and supply their data sets for re-analysis. The IPD meta-analysis included 30 trials with data from 9,936 women and 14,477 babies.
Researchers analyzed singleton and multiple gestation pregnancies separately and compared each form of progestogen with placebo or no intervention. They then compared injectable 17α-hydroxyprogesterone caproate (17-OHPC) with vaginal progesterone using network meta-analysis.
Women who had experienced PTB and members of patient and family advocacy organizations were part of the collaborative group.
Results
Singleton pregnancies at high risk for PTB, mostly due to prior PTB or short cervix.
Compared with untreated women, women who received injectable 17-OHPC
- Were less likely to have babies who were born before 34 weeks (risk ratio [RR]=0.74; 95% confidence interval [CI]: 0.59, 0.94)
- Had reduced risk of perinatal death, but this was very uncertain (RR=0.88; 95% CI: 0.54, 1.45)
- Were more likely to experience maternal complications (RR=1.34; 95% CI: 1.06, 1.71)
- Had babies with reduced risk of serious neonatal complications, but this was uncertain (RR=0.76; 95% CI: 0.54, 1.08)
Compared with untreated women, women who received vaginal progesterone
- Were less likely to have babies who were born before 34 weeks (RR=0.78; 95% CI: 0.68, 0.90)
- Had reduced risk of perinatal death, but this was uncertain (RR=0.74; 95% CI: 0.52, 1.07)
- Were more likely to have maternal complications, but this was uncertain (RR=1.14; 95% CI: 0.93, 1.40)
- Had babies with reduced risk of serious neonatal complications, but this was uncertain (RR=0.82; 95% CI: 0.65, 1.04)
Comparing 17-OHPC with vaginal progesterone, network meta-analysis found no clear evidence that either was more effective in reducing PTB before 34 weeks, serious neonatal complications, overall maternal complications, or perinatal death.
Evidence for oral progesterone was insufficient.
Multiple gestation pregnancies, mostly with no additional risk factors
Overall, the study found no evidence that 17-OHPC or vaginal progesterone reduced PTB before 34 weeks or associated complications in unselected multifetal pregnancies. Data were too few for reliable analysis of women with additional risk factors.
Limitations
A large trial of 17-OHPC in singleton pregnancies was completed after this meta-analysis. Incorporating these and other new trial data could change the estimated effects. Only two trials directly compared 17-OHPC with vaginal progesterone. The meta-analysis mainly used indirect evidence from trials comparing progestogens with placebo or no treatment.
Conclusions and Relevance
For women with singleton pregnancies with a previous PTB or short cervix, both 17-OHPC and vaginal progesterone reduced the risk of PTB before 34 weeks and improved other birth and neonatal outcomes. However, 17-OHPC increased overall maternal complications. Maternal complications also increased with vaginal progesterone, but this effect was smaller and more uncertain. The findings do not support the use of progestogens in unselected twin or triplet pregnancies.
Future Research Needs
This meta-analysis should be updated to include newly completed trials, including the recent large trial of 17-OHPC. Depending on the results of an update, further trials comparing vaginal progesterone, 17-OHPC, and potentially oral progesterone may be needed.
