From the moment of birth, infants born extremely preterm or at an extremely low birth weight (<1000 g) face critical illness due to multiorgan system immaturity, typically requiring hospitalization in the neonatal intensive care unit (NICU) for several months. Medical interventions now allow most of these infants to survive to hospital discharge, and the focus has shifted to identifying interventions that reduce adverse health and developmental consequences during childhood and beyond. With this goal in mind, the highly controlled NICU diet offers a feasible target for intervention, with the potential to optimize ex utero brain development during the critical period in the third trimester that coincides with the NICU hospitalization.