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Objective: To assess the relationship between cigarette smoking during pregnancy and very preterm births, according to the main mechanisms of preterm birth.Design: Case-control study (the French Epipage study).Setting: Regionally defined population of births in France.Population: Eight hundred and sixty-four very preterm live-born singletons (between 27 and 32 completed weeks of gestation) and 567 unmatched full-term controls.Methods: Data from the French Epipage study were analysed using a polytomous logistic regression model to control for social and demographic characteristics, pre-pregnancy body mass index and obstetric history. The main mechanisms of preterm delivery were classified as gestational hypertension, antepartum haemorrhage, premature rupture of membranes, spontaneous preterm labour and other miscellaneous mechanisms.Main Outcome Measures: Odds ratios for very preterm birth for low to moderate (1-9 cigarettes/day) and heavy (>/=10 cigarettes/day) maternal smoking in pregnancy, estimated according to the main mechanisms leading to preterm birth.Results: Smokers were more likely to give birth to very preterm infants than non-smokers [adjusted odds ratio (aOR) 1.7, 95% confidence interval (CI) 1.3-2.2]. Heavy smoking significantly reduced the risk of very preterm birth due to gestational hypertension (aOR 0.5, 95% CI 0.3-1.0), whereas both low to moderate and heavy smoking increased the risk of very preterm birth due to all other mechanisms (aOR between 1.6 and 2.8).Conclusion: These data from the Epipage study show that maternal smoking during pregnancy is a risk factor for very preterm birth. The impact of maternal smoking on very preterm birth appears to be complex: it lowers the risk of very preterm birth due to gestational hypertension, but increases the risk of very preterm birth due to other mechanisms. These findings might explain why maternal smoking is more closely related to preterm birth among multiparous women than among nulliparous women. [ABSTRACT FROM AUTHOR]