A randomised controlled double-blind clinical trial of 17-hydroxyprogesterone caproate for the prevention of preterm birth in twin gestation (PROGESTWIN): evidence for reduced neonatal morbidity

BJOG. 2015 Jan;122(1):71-9. doi: 10.1111/1471-0528.13031. Epub 2014 Aug 27.

Abstract

Objective: To determine whether 17 alpha-hydroxyprogesterone caproate (17OHPC) prolongs gestation beyond 37 weeks of gestation (primary outcome) and reduces neonatal morbidity (secondary outcome) in twin pregnancy.

Design: Randomised controlled double-blind clinical trial.

Setting: Tertiary-care university medical centre.

Population: Unselected women with twin pregnancies.

Methods: Participants received weekly injections of 250 mg 17OHPC (n = 194) or placebo (n = 94), from 16-20 to 36 weeks of gestation. Randomisation was performed using the permuted-block randomisation method. Data were analysed on an intention-to-treat basis.

Main outcome measure: Preterm birth (PTB) rate before 37 weeks of gestation.

Results: There were no significant differences in the average gestational age at delivery, or in the rates of PTB before 37, 32, and 28 weeks of gestation, between the two groups. The proportion of very-low-birthweight neonates (<1500 g) was significantly lower in the 17OHPC group (7.6%) compared with placebo (14.3%) (relative risk, RR 0.5; 95% confidence interval, 95% CI 0.3-0.9; P = 0.01). Progestogen-treated neonates had a significantly lower composite neonatal morbidity (19.1%) compared with placebo (30.9%) (odds ratio, OR 0.53; 95% CI 0.31-0.90; P = 0.02), with significantly lower odds for respiratory distress syndrome (14.4 versus 23.4%; OR 0.55; 95% CI 0.31-0.98; P = 0.04), retinopathy of prematurity (1.1 versus 4.6%; OR 0.21; 95% CI 0.05-0.96; P = 0.04), and culture-confirmed sepsis (3.4 versus 12.8%; OR 0.24; 95% CI 0.10-0.57; P = 0.00).

Conclusions: Intramuscular 17OHPC therapy did not reduce PTB before 37 weeks of gestation in unselected twin pregnancies. Nonetheless, 17OHPC significantly reduced neonatal morbidity parameters and increased birthweight.

Keywords: 17-Alpha-hydroxyprogesterone caproate; preterm birth; prevention; progestogens; twin gestation.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 17 alpha-Hydroxyprogesterone Caproate
  • Adult
  • Double-Blind Method
  • Female
  • Gestational Age
  • Humans
  • Hydroxyprogesterones / therapeutic use*
  • Infant, Newborn
  • Infant, Premature
  • Infant, Very Low Birth Weight
  • Injections, Intramuscular
  • Odds Ratio
  • Pregnancy
  • Pregnancy Trimester, Second
  • Pregnancy Trimester, Third
  • Pregnancy, Twin*
  • Premature Birth / prevention & control*
  • Progestins / therapeutic use*
  • Respiratory Distress Syndrome, Newborn / prevention & control*
  • Retinopathy of Prematurity / prevention & control*
  • Sepsis / prevention & control*

Substances

  • Hydroxyprogesterones
  • Progestins
  • 17 alpha-Hydroxyprogesterone Caproate