Substance use in PRegnancy and the mOrbidity Mortality rISk Environment (PROMISE) - Abstract: People who use drugs (PWUD) and are pregnant or postpartum are trying to survive at the intersection of 2 of the gravest public health crises confronting the 21st century US: epidemics of (1) drug-related harms, and (2) maternal morbidity and mortality. The US has the highest rate of maternal mortality of all high-income countries, and analyses of death certificates suggest that 11% of deaths during pregnancy and17% of postpartum deaths are drug-related. This crisis is escalating: rates of opioid use disorder diagnosis at delivery quintupled between 2004-2015, and rates of amphetamine-related diagnosis at delivery doubled. In the midst of this escalating crisis, public health has failed to adequately mobilize. Intervention develop- ment is stymied by limited evidence about which harms PWUD suffer while pregnant or postpartum. Tailoring and locating interventions is challenging, because we know exceptionally little about who suffers these harms, overall or among structurally marginalized subpopulations; about where PWUD suffering these harms cluster spatially; or about when during the highly dynamic 21 months of pregnancy and the postpartum year they suf- fer them. Further, few studies have identified intervention targets: the decades of “risk environment” research about why PWUD in the general (i.e., not pregnant or postpartum) population experience specific drug-related harms has rarely focused on pregnant/ postpartum people. By generating essential evidence that answers these fundamental questions, the proposed longitudinal study is designed to support a new arena of interventions to help PWUD survive the 21 months they are pregnant and postpartum. By using rigorous methods to analyze a novel longitudinal hospital database spanning 17 states from 2017-2022 and a recently created CDC maternal mortality database spanning 36 states in 2018-2022, we will generate panoramic evi- dence about (1a) the incidences of hospital encounters for specific drug-related morbidities across the 7 quar- ters PWUD are pregnant and postpartum, overall and by race/ ethnicity, insurance status, and rurality, and (1b) spatiotemporal variations in these incidences; and about (2a) the incidences of drug-related maternal mortality, overall and by race/ethnicity, insurance status, and rurality; and (2b) spatiotemporal variations in these inci- dences. Guided by the Intersectional Risk Environment Model, we will next (3) apply Bayesian models to iden- tify risk environment features correlated with spatiotemporal variations in these morbidity and mortality inci- dences, overall and by race/ethnicity, insurance status, and rurality. A National Advisory Board of PWUD, harm reduction advocates, and reproductive justice advocates, and representatives of state agencies and Maternal Mortality Review Committees, will inform the construction of Aim 1&2 incidence measures; prioritize which risk environment features to analyze in Aim 3&4; and support dissemination of Aim 1-4 results so they rapidly in- form the development of interventions to help PWUD survive the 21 months they are pregnant and postpartum.