A 5-year retrospective cohort study ( n = 4,178) was conducted to identify trends and outcomes associated with child welfare-involved maternal-infant dyads affected by perinatal substance use in Colorado. Two linked data sources were used: (1) vital records birth and death certificate data on live births between 2013 and 2019 and (2) child welfare data from the Statewide Automated Child Welfare Information System. Data integration and deidentification work was accomplished by the Linked Information Network of Colorado and authorized by state legislation. Two tools were available for identity resolution: (1) the Senzing identity resolution application and (2) SQL queries. Binary logistic regression was used to explore how a birthing person 's demographic characteristics, use of prenatal care, Special Nutrition Program for Woman, Infants, and Children (WIC) enrollment during pregnancy, health of birthing person during pregnancy and delivery, and the newborn 's health at the time of birth related to child welfare removal within the first 60 days. Factors associated with an increased risk of infant removal include less than adequate prenatal care, lower household income, low participation in WIC, and greater medical fragility of the newborn. For infants removed from the home, the rate of placement with relatives while in foster care decreased by 15 % (2016 -2019) . This is a concern as placing children with relatives is shown to promote healthy child development. Findings bring into focus opportunities for prevention, treatment, and support of maternal-infant dyads affected by substance use during the perinatal period and offers insight into early entry points for preventing the need for family separation by child welfare.