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Background: Preterm infants (PIs) are more susceptible to neurodevelopmental impairment compared with term newborns. Adequate postnatal growth has been associated with improved neurocognitive outcomes; therefore, optimization of nutrition may positively impact the neurodevelopment of PIs., Objective: This study focused on macronutrient parenteral nutrition (PN) intake during the Neonatal Intensive Care Unit stay and their associations with neurodevelopmental outcomes in PIs in the first two years of life., Methods: The Embase, MEDLINE, and Cochrane Library databases were searched using the following subject headings and terms (MeSH): "premature infants", "parenteral nutrition", "growth", "brain", "neurodevelopment", and "central nervous system diseases". All relevant papers' reference lists were manually searched. PN and neurodevelopment studies concerning the first two years of life were collected and analyzed., Results: 275 potential studies were retrieved, 64 were selected for full-text reading, and 22 were included (12 randomized controlled trials). While glucose intakes should be immediately provided and strictly monitored avoiding hyperglycemia, the long-term outcomes of aggressive PN caloric intakes are uncertain. Early amino acid (AA) supplementation is mandatory and improves short-term growth, though it is questionable whether increased AA and better neurodevelopment are directly related. Lipid infusion should be initiated right after birth, and further investigation will enable us to ascertain the potential impacts of lipid emulsions, particularly fish oil, on PI neurodevelopment., Conclusions: An aggressive PN and its possible metabolic complication could not favor neurodevelopment; the way forward could be a customized approach, depending on the patient's clinical state and tolerance. Long-term follow-up studies and the search for specific markers of tolerance are warranted.