After completing this article, readers should be able to: 1. Characterize the incidence of severe neurodevelopmental handicaps in very low-birthweight infants over the past decade. 2. Define severe neurodevelopmental deficits. 3. Characterize the derivation of the brain and the epidermis. 4. Describe the possibilities of evoked potential testing for evaluation of brain function in asphyxiated and very low-birthweight preterm infants. 5. Characterize in utero development of the high electrical resistance of skin. “Compared with newborns of other species, the human neonate is relatively helpless in motor capabilities and relatively precocious in sensory capabilities.” —T. Berry Brazelton Behavioral Competence Avery’s Neonatology . 5th ed. 1999 Accumulating evidence suggests a connection between the developing brain and the developing skin. In this view, the skin, broadly considered, functions as a neurodevelopmental boundary in the very low-birthweight (VLBW) preterm infant. The epidermis, for example, plays a role as a specialized ectodermal derivative closely linked to both neuroperception and noninvasive monitoring in intensive care environments. The terminal differentiation product of the epidermis, the stratum corneum, is considered a prototypical smart material. The concept of the skin as a neurodevelopmental interface may be broadened to include its role as an interface with the caregiver and a boundary for primary care delivery in the neonatal intensive care unit. Recent reviews have demonstrated the persistence of a high incidence of severe neurodevelopmental disability in VLBW preterm infants (Fig 1⇓ ). (1) Severe neurodevelopmental disability generally is defined as subnormal cognitive function, cerebral palsy, blindness, deafness, or a combination of these factors. The continuing high incidence of neurodevelopmental handicap raises several questions: 1) Given the complexity and relative inaccessibility of the central nervous system (CNS), is it advantageous to consider alternative viewpoints for the etiology and therapy of neurodevelopmental handicaps? 2) Given the close embryologic connection between brain and skin, should cognition be …