Objectives: To assess the relation between cigarette smoking during pregnancy and neonatal respiratory distress syndrome (RDS) in very preterm birth, and to a nalyse the differential effect of antenatal steroids on RDS among smokers and no nsmokers. Design: A population based cohort study (the French Epipage study). Se tting: Regionally defined births in France. Methods: A total of 858 very preterm liveborn singletons (27-32 completed weeks of gestation) of the French Epipage study were included in this analysis. The odds ratio for RDS in relation to smo king in pregnancywas estimated using a logistic regression to control for gestat ional age. The odds ratio for RDS in relation to antenatal steroids was estimate d taking into account an interaction between antenatal steroids and cigarette sm oking, using multiple logistic regression to control for gestational age, birthw eight ratio, main causes of preterm birth, mode of delivery, and sex. Results: T he odds ratio for RDS in relation to smoking in pregnancy adjusted for gestational age (aOR)was 0.59 (95%confidence interval (Cl) 0.4 4 to 0.79). The aOR for RDS in relation to antenatal steroids was 0.31 (95%Cl 0.19 to 0.49) in babies born to non-smokers and 0.63 (95%Cl 0.38 to 1.05 ) in those born to smokers; the difference was significant (p = 0.04). Conclusi ons: Cigarette smoking during pregnancy is associated with a decrease in the ris k of RDS in very preterm babies. Although antenatal steroids reduce the risk of RDS in babies born to both smokers and non-smokers, the reduction is smaller in those born to smokers. Objectives: To assess the relation between cigarette smoking during pregnancy and neonatal respiratory distress syndrome (RDS) in very preterm birth, and to a nalyse the differential effect of antenatal steroids on RDS among smokers and no nsmokers. Design: A population based cohort study ( the French Epipage study). Seting: Regionally defined births in France. Methods: A total of 858 very preterm liveborn singletons (27-32 completed weeks of gestation) of the French Epipage study were included in this analysis. The odds ratio for RDS in relation to smo king in pregnancywas estimated using a logistic regression to control for gestat ional age. The odds ratio for RDS in relation to antenatal steroids was estimated d taking into account an interaction between antenatal steroids and cigarette sm oking, using multiple logistic regression to control for gestational age, birthw eight ratio, primary causes of preterm birth, mode of delivery, and sex. Results: T he odds ratio for RDS in relation to a smoking in pregnancy adjusted for gestational age (aOR) was 0.59 (95% confidence interval (Cl) 0.4 4 to 0.79). The aOR for RDS in relation to antenatal steroids was 0.31 (95% Cl 0.19 to 0.49) in babies born to non-smokers and 0.63 (95% Cl 0.38 to 1.05) in those born to smokers; the difference was significant (p = 0.04). Conclusi ons: Cigarette smoking during pregnancy is associated with a decrease in the ris k of RDS in very preterm babies with antenatal steroids reduce the risk of RDS in babies born to both smokers and non-smokers, the reduction is smaller in those born to smokers.