A systematic review and meta‐analysis of randomized controlled trials comparing 17‐alpha‐hydroxyprogesterone caproate versus placebo for the prevention of recurrent preterm birth

• Published in: International journal of gynecology and obstetrics Vol. 147; no. 2; pp. 156 - 164
• Main Authors: Fernandez‐Macias, Rosa, Martinez‐Portilla, Raigam J., Cerrillos, Lucas, Figueras, Francesc, Palacio, Montse
• Format: Journal Article
• Language: English
• Published: United States 01-11-2019
• Subjects: 17 alpha-Hydroxyprogesterone Caproate - therapeutic use; 17‐alpha‐hydroxyprogesterone caproate; Adult; Female; Humans; Infant, Newborn; Intramuscular progesterone; Meta‐analysis; Perinatal Death - prevention & control; Pregnancy; Pregnancy Trimester, Second; Premature Birth - prevention & control; Preterm birth; Randomized Controlled Trials as Topic; Recurrent preterm birth; Systematic review; 17-alpha-hydroxyprogesterone caproate; Systematic review; Preterm birth; Recurrent preterm birth; Intramuscular progesterone; Meta-analysis
• ISSN: 0020-7292; 1879-3479
• DOI: 10.1002/ijgo.12940

Background
Preterm birth causes an increased risk for perinatal morbidity and mortality.
Objective
To determine whether mid‐trimester 17‐alpha‐hydroxyprogesterone caproate (17‐OHPC) reduces the risk of recurrent preterm birth and adverse perinatal outcomes.
Search strategy
Systematic search to identify relevant studies published in different languages, registered after 2000, using appropriate MeSH terms.
Selection criteria
Inclusion criteria were women between 16 and 26+6 weeks of pregnancy with history of preterm delivery in any pregnancy randomized to either 17‐OHPC or placebo/no treatment.
Data collection and analysis
The number of preterm births and adverse outcomes in the 17‐OHPC and placebo arms over the total number of patients in each randomized group were used to calculate the risk ratio (RR) by random‐effects models using the Mantel‐Haenszel method. Between‐study heterogeneity was assessed using tau2, χ2 (Cochrane Q), and I2 statistics.
Main results
Four studies were included. There was a 29% (RR 0.71; 95% CI, 0.53–0.96; P=0.001), 26% (RR 0.74; 95% CI, 0.58–0.96; P=0.021), and 40% (RR 0.60; 95% CI, 0.42–0.85; P=0.004) reduction in recurrent preterm birth at <37, <35, and <32 weeks, respectively, in the 17‐OHPC group compared with placebo. The reduction in neonatal death was 68% (RR 0.32; 95% CI, 0.15–0.66; P=0.002).
Conclusions
17‐OHPC could reduce the risk of recurrent preterm birth at <37, <35, and <28 weeks and neonatal death.
PROSPERO: CDR42017082190
When initiated from 16–26+6 weeks of pregnancy, 17‐alpha‐hydroxyprogesterone caproate reduces the risk of recurrent preterm before 37 weeks of pregnancy and neonatal death compared with placebo or no treatment.