BACKGROUND: Children born at low gestational ages face a range of risks and number of neonates surviving very preterm birth is increasing. We present the objectives and methods of a French national cohort of very and moderately preterm children, the EPIPAGE 2 study. It aims to examine short- and long-term outcomes of very preterm children and their determinants.Methods/design: Eligible participants for this prospective population-based study include all infants live born or stillborn and all terminations of pregnancy between 22 and 31 completed weeks of gestation in all the maternity units in 25 French regions. In addition, a sample of moderate preterm births, i.e. births and late terminations at 32-34 weeks, was included in the same regions. In all, 7804 babies (stillbirths and live births) and terminations of pregnancy out of 8400 eligible births in France in 2011 that were either very (22-31 weeks) or moderately preterm (32-34 weeks) were included. Data on pregnancy, delivery, and neonatal events were extracted from the obstetric and neonatal records. The follow-up will collect information at corrected ages of one and 2 years and at 5, 8, and 12 years of age. Of the 4467 children discharged alive from the hospital and eligible for follow-up, 155 (4%) families refused further follow-up and 22 died before one-year of age. Finally, 4290 were included in the follow-up.Eight additional projects investigating specific hypotheses among subsamples of the cohort by collecting specific data in addition to the core cohort data are being conducted to investigate 1) diagnosis of histologic chorioamnionitis, 2) early biomarkers of child health, 3) attitudes of care for extremely preterm infants, 4) painful procedures in neonatal intensive care units, 5) neonatal MRI cerebral abnormalities and their relation to executive functions, 6) associations between early gut colonization and early and late onset diseases, 7) impact of neonatal nutrition on child development, and 8) mother-infant attachment. DISCUSSION: This project seeks to provide new data on the prognosis and etiology of very preterm birth and to assess related medical practices. Accordingly, it should lead to the development of new strategies of management and prevention in high-risk babies.