Background: There are few studies exploring the pathophysiological pathways that may condition differentially the emergence/course of neurodevelopmental disorders (ND) in very preterm and extremely preterm newborns (VPTN/EPTN). Furthermore, there are no established biological markers predictive of ND in this population. The aim of this study is four-fold: in two cohorts of VPTN/EPTN (i) to characterize the emergence/course of ND up to corrected-age 6 years, (ii) to identify those factors (from prenatal stages up to age 6 years) that explain the interindividual differences related to emergence/course of ND, (iii) to identify in the first hours/days of life a urinary metabolomic biomarker profile predictive of ND, and (iv) to determine longitudinally variations in DNA methylation patterns predictive of ND. Methods: Observational, longitudinal, prospective, six-year follow-up, multicentre collaborative study. Two cohorts are being recruited: the PeriSTRESS-Valencia-cohort (n = 26 VPTN, 18 EPTN, and 122 born-at-term controls), and the PremTEA-Madrid-cohort (n = 49 EPTN and n = 29 controls). Results: We describe the rationale, objectives and design of the PeriSTRESS-PremTEA project and show a description at birth of the recruited samples. Conclusions: The PeriSTRESS-PremTEA project could help improve early identification of clinical, environmental and biological variables involved in the physiopathology of ND in VPTN/EPTN. It could also help to improve the early identification of non-invasive ND biomarkers in this population. This may allow early ND detection as well as early and personalised intervention for these children.