PROJECT SUMMARY/ABSTRACT The prevalence of opioid use disorder (OUD) during pregnancy has increased by nearly 500% over the past 15 years. While pregnancy presents a strong motivation for seeking and complying with OUD treatment, the postpartum period is associated with a high risk for relapse. Indeed, up to 80% of women with OUD relapse to illicit opioid use within six months of delivery. Relapse leads to a wide range of negative health and social outcomes for both the infant, mother, and entire family, such as physical (e.g., fatal and non-fatal overdose, increased risk of substance use disorders in children), emotional (e.g., anxiety, depression), and social (e.g., foster care placement, poor academic achievement) consequences. Unfortunately, little research is available on how to prevent postpartum opioid relapse. A wide-range of hormones (e.g., cortisol, progesterone, oxytocin) have been linked to substance use disorders and infant caregiving activities. While hormones have the potential to significantly reduce the risk for postpartum relapse, methodological limitations (e.g., single hormone assessment, limited time assessment), content limitations (e.g., opioid use, polysubstance use), and a lack of dissemination of knowledge across disciplines are all limiting this use of this potentially highly impactful approach. Therefore, my overall goal is to use new technologies and methodologies to directly address the current limitations and enhance the cross-discipline dissemination of knowledge to utilize hormonal level(s)/pattern(s) to protect against opioid relapse during the high-risk postpartum period. To achieve this goal, this New Innovator Award will address four objectives: (1) measure hormones, infant caregiving activities, relapse risk factors, and OUD-related outcomes during the postpartum period using a prospective cohort study design, (2) identify hormonal level(s)/pattern(s) that are predictive of postpartum opioid use via with data-driven predictive analytics, (3) examine methods to elicit/identify targeted hormone level(s)/pattern(s) using specific infant caregiving activities, exogenous hormone delivery, and/or continuous/frequent hormone monitoring, and (4) preliminarily assess the link between the identified hormonal level(s)/pattern(s) and OUD-related outcomes. Upon completion of this high-risk/high-reward project, I will either (a) be able to rule out a hormonally-based intervention as an element of a comprehensive behavioral-psycho-social approach to prevent postpartum opioid relapse, or (b) have strong preliminary evidence for the use of hormone level(s)/pattern(s) to prevent postpartum opioid relapse. Further, this work will be ripe for expansion to other substances of abuse (e.g., cannabis), as well as application to other postpartum health issues (e.g., depression, anxiety).