We present the Anterior Modifiers in the Emergence of Neurodevelopmental Disorders (AMEND) framework, designed to reframe the field of prospective studies of neurodevelopmental disorders. In AMEND we propose conceptual, statistical and methodological approaches to separating markers of early-stage perturbations from later developmental modifiers. We describe the evidence for, and features of, these interacting components before outlining analytical approaches to studying how different profiles of early perturbations and later modifiers interact to produce phenotypic outcomes. We suggest this approach could both advance our theoretical understanding and clinical approach to the emergence of developmental psychopathology in early childhood.