ABSTRACT Childhood maltreatment (CM) has highly deleterious effects on human development and is arguably the most influential, preventable cause of enduring psychopathology in the U.S. Infants and young children are at particularly high risk for physical harm from abuse and neglect, comprising over 60% of all child maltreatment fatalities. An increasing number of studies point to the ability to target prevention of CM by estimating individual-specific risk at the time of birth, on the basis of readily-available variables in birth records. The prospect of real-time identification of newborns at risk for CM on the basis of risk indicators available in obstetrical settings to be able to target prevention is exciting, but empirical testing of feasibility and predictive utility of methods are key to any systematic attempt to integrate this in U.S. obstetric or newborn clinical services. For example, birth record indices still identify a substantial number of children who do not go on to experience CM, making it important to attempt to optimize specificity (preserving sensitivity) with additional brief clinical screens or administrative data predictive risk modeling prior to broad implementation. Moreover, since screening is only as valuable as its actionability, it is important to understand whether screening results in uptake of needed preventive intervention and, in turn, whether this decreases actual CM. In a sample of 400 families enriched for risk for future CM, we contrast the predictive utility of three types of newborn screening for risk of future official-report of CM involving: a) birth record risk variables (BRRV) only; b) BRRV plus a brief clinical screen for maternal mental health and substance use status, childhood trauma and/or current intimate partner violence; and c) retrieval and analysis of a set of medical record and insurance claims variables (for each family) based on those included in a large-scale PRM effort of a separate Capstone center project during the study period. A RCT pilot arm of the study will explore the extent to which a brief, personalized education protocol for the primary caregiver enhances his/her engagement in intervention over care as usual. A second major aim of the project is to advance scientific understanding of the relationship between risk and outcome. Despite the established association between CM and psychopathology, the associated paths and mechanisms are still being identified, calling for more longitudinal investigation with the hope of identifying modifiable factors that can be targeted for intervention when prevention efforts are not successful. We will first determine whether CM report (as a primary outcome) is moderated by participation in services and/or changes in modifiable risk factors over the first 6 months of life. Next we will explore the extent to which infant developmental outcomes are moderated not only by CM, but by early psychobiological indices of vulnerability to its adverse consequences. The project responds to several priorities of the Capstone RFA (RFA-HD-18-012) as well as the mission of Center for Innovation in Child Maltreatment Policy, Research, and Training to prevent CM and promote healthy development of victims of abuse and neglect.