Impact of the use of antenatal corticosteroids on mortality, cerebral lesions and 5-year neurodevelopmental outcomes of very preterm infants: the EPIPAGE cohort study


  • *

    EPIPAGE Study Group: INSERM U149: B Larroque (national coordinator), PY Ancel, B Blondel, G Bréart, M Dehan, M Garel, M Kaminski, F Maillard, C du Mazaubrun, P Missy, F Sehili, K Supernant; Alsace: M Durand, J Matis, J Messer, A Treisser (Hôpital de Hautepierre, Strasbourg, France); Franche-Comté: A Burguet, L Abraham-Lerat, A Menget, P Roth, J-P Schaal, G Thiriez (CHU St Jacques, Besançon, France); Haute-Normandie: C Lévêque, S Marret, L Marpeau (Hôpital Charles Nicolle, Rouen, France); Languedoc-Roussillon: P Boulot, J-C Picaud (Hôpital Arnaud de Villeneuve, Montpellier), A-M Donadio, B Ledésert (ORS Montpellier, France); Lorraine: M André, J Fresson, JM Hascoët (Maternité Régionale, Nancy, France); Midi-Pyrénées: C Arnaud, S Bourdet-Loubère, H Grandjean (INSERM U558, Toulouse), M Rolland (Hôpital des Enfants, Toulouse, France); Nord-Pas-de-Calais: C Leignel, P Lequien, V Pierrat, F Puech, D Subtil, P Truffert (Hôpital Jeanne de Flandre, Lille, France); Pays-de-Loire: G Boog, V Rouger-Bureau, J-C Rozé (Hôpital Mère-Enfant, Nantes, France); Paris-Petite-Couronne: PY Ancel, G Bréart, M Kaminski, C du Mazaubrun (INSERM U149, Paris, France); M Dehan, V Zupan-Simunek (Hôpital Antoine Béclère, Clamart, France); M Vodovar, M Voyer (Institut de Puériculture, Paris, France).

Dr L Foix-L’Hélias, INSERM, U149, 16 avenue Paul Vaillant Couturier, 94807 Villejuif Cedex, France. Email:


Objective  To assess the impact of antenatal corticosteroids (ACS) on neonatal mortality, cerebral lesions and 5-year neurodevelopmental outcome of infants born at 24–27 and 28–32 weeks of gestational age (GA).

Design  Observational population-based study including all births at GAs between 22 and 32 weeks in 1997 in nine regions of France. Survivors were assessed at the age of 5 years.

Sample and methods  The population enrolled in the follow up comprised 2323 infants; there were 23 deaths before age 5 years and outcome at 5 years was available for up to 1781 subjects. Two GA subgroups (24–27 and 28–32 weeks of GA) were analysed separately. Propensity scores were used to reduce bias in the estimation of the association between ACS treatment and outcomes.

Main outcome measures  Neonatal death, neonatal white matter injury, cerebral palsy, mental processing composite (MPC) of the Kaufman Assessment Battery for Children test and behavioural difficulties at 5 years.

Results  In the 28- to 32-week GA subgroup, there was a significant association between ACS and a decreased risk of both neonatal death (OR = 0.61 [0.41–0.91]) and white matter injury (OR = 0.60 [0.46–0.79]) but only a nonsignificant trend for improved 5-year outcome (cerebral palsy, MPC < 70). In the 24- to 27-week GA subgroup, ACS was associated with a significant decrease risk of neonatal death (OR = 0.43 [0.27–0.68]) but there was only a trend for a lower risk of white matter injury and no beneficial impact on outcome at 5 years. Limiting the analysis to only those who received complete courses of ACS did not modify the results.

Conclusion  The study shows that ACS therapy greatly increases the survival of very preterm infants, including the most immature, but there is little evidence that ACS affects long-term neurodevelopmental and behavioural outcome in 28- to 32-week survivors, and none in <28-week survivors.