Efficacy of antenatal corticosteroids in preterm twins: the EPIPAGE-2 cohort study

BJOG. 2018 Aug;125(9):1164-1170. doi: 10.1111/1471-0528.15014. Epub 2017 Dec 14.


Objectives: To investigate the efficacy of antenatal corticosteroid (ACS) therapy on short-term neonatal outcomes in preterm twins, and further document the influence of the ACS-to-delivery interval.

Design: EPIPAGE-2 is a nationwide observational multicentre prospective cohort study of neonates born between 22 and 34 completed weeks of gestation.

Setting: All French maternity units, except in a single administrative region, between March and December 2011.

Population: A total of 750 twin neonates born between 24 and 31 weeks of gestation.

Methods: Exposure to ACSs was examined in four groups: single complete course, with an ACS administration-to-delivery interval of ≤7 days; single complete course, with an ACS-to-delivery interval of >7 days; repeated courses; or no ACS treatment.

Main outcome measures: Neonatal outcomes analysed were severe bronchopulmonary dysplasia, periventricular leukomalacia or intraventricular haemorrhage grade III/IV, in-hospital mortality, and a composite indicator of severe outcomes.

Results: Compared with no ACSs, in multivariable analysis, a single course of ACSs with an administration-to-delivery interval of ≤7 days was significantly associated with a reduced rate of periventricular leukomalacia or intraventricular haemorrhage grade III/IV (aOR 0.2; CI 95% 0.1-0.5), in-hospital mortality (0.3; 0.1-0.6), and the composite indicator (0.1; 0.1-0.3), whereas a single course of ACDs with an administration-to-delivery interval of >7 days did not significantly reduce the frequency of in-hospital mortality (0.7; 0.3-1.8). No significant differences in terms of benefit or risk were found when comparing repeated courses with a single complete course.

Conclusion: In preterm twins, a single complete course of antenatal corticosteroids was associated with an improvement of severe neurological outcome, whereas reduced in-hospital mortality was seen only when the ACS-to-delivery interval was ≤7 days.

Tweetable abstract: A single complete course of antenatal steroids reduced severe neurological morbidity in preterm twins (24-31 weeks).

Keywords: Antenatal corticosteroids; betamethasone; prematurity; preterm birth; preterm delivery; short-term morbidity; steroid-to-delivery interval; twin pregnancy; twins.

Publication types

  • Multicenter Study
  • Observational Study

MeSH terms

  • Adrenal Cortex Hormones / administration & dosage*
  • Bronchopulmonary Dysplasia
  • Cerebral Intraventricular Hemorrhage / etiology
  • Cerebral Intraventricular Hemorrhage / prevention & control
  • Diseases in Twins / etiology
  • Diseases in Twins / prevention & control*
  • Drug Administration Schedule
  • Female
  • Humans
  • Infant, Newborn
  • Infant, Premature
  • Infant, Premature, Diseases / etiology
  • Infant, Premature, Diseases / prevention & control*
  • Leukomalacia, Periventricular / etiology
  • Leukomalacia, Periventricular / prevention & control
  • Male
  • Perinatal Mortality
  • Pregnancy
  • Premature Birth / etiology
  • Premature Birth / prevention & control*
  • Prenatal Care / methods*
  • Prospective Studies
  • Time Factors
  • Treatment Outcome
  • Twins*


  • Adrenal Cortex Hormones