Project led by Digna Velez Edwards

This research project will use a community engaged approach to illuminate knowledge of, attitudes about, and priorities for pharmacogenomics, and validate pharmacogenomic associations for maternal and pediatric populations using the innovative and generalizable strategy of electronic health records-based phenotyping.

Background: The field of pharmacogenomics has progressed from the discovery of genetic variants that cause variable function of drug metabolism enzymes to a cornerstone of clinical precision medicine. However, there are limited data supporting drug-gene associations for children and for women during and after pregnancy. The unique physiology of childhood and pregnancy demand validation of pharmacogenomic signals prior to clinical implementation. These knowledge gaps are compounded for individuals from minority populations, who have been underrepresented and thus underserved by genomic research and specifically pharmacogenomic studies.

The primary objective of this project is to advance research and support clinical implementation in pharmacogenomics for children and pregnant women. Our work will use a community engaged approach to:

1. Illuminate knowledge of, attitudes about, and priorities for pharmacogenomics.
2. Validate pharmacogenomic associations for pediatric and maternal populations.

• Aim 1 will assess the knowledge and attitudes regarding pharmacogenomic testing among diverse cohorts of children with chronic disease and pregnant women, before and after receiving pharmacogenomic test results. This aim will begin with a Community Engagement Studio to identify strategies to facilitate and enhance inclusion of children with chronic health conditions, pregnant women, individuals from minority populations, and those with disabilities in pharmacogenomic research. We will then perform surveys before and after pharmacogenomic testing and return of results.

• Aim 2 will leverage our large biobank resource to validate drug-gene interactions in women and children to enable evidence-based clinical implementation for these populations and identify novel signals for further study. This aim will generate electronic health records phenotyping methods and tools to efficiently complete the aim and facilitate future research at our site and others.

Learn more about pharmacogenomics in the pediatric population at the Center for Pediatric Precision Medicine.

Project led by Stephen Patrick

The purpose of this research project is to develop and validate electronic health records-based algorithms to identify a cohort of opioid-exposed infants and their mothers (dyads); and create a novel linkage of these data to state-wide data test the hypothesis that use of medications for opioid use disorder is associated with improved early outcomes and tes the hypothesis that opioid use disorder treatment is associated with improvements in the novel longitudinal outcome of dyadic stability.

Background: Opioid use and diagnoses of opioid use disorder (OUD) among pregnant women in the US rose substantially over the last 20 years with a concurrent increase in rates and of neonatal opioid withdrawal syndrome (NOWS). Several key knowledge gaps remain in our understanding of how neonatal and postpartum treatment affect the maternal-infant dyad. In a 2016 NICHD workshop, stakeholders pointed to the potential for precision medicine to tailor therapeutics for the dyad. There is an urgent need to leverage existing data systems to conduct cutting-edge data science research that generates novel, holistic approaches for the maternal-infant dyad and accelerates research on maternal and pediatric therapeutics.

This project will use existing linkages to multiple sources of data to fill critical knowledge gaps for the dyad and will use novel data science methodology to create scalable algorithms to accelerate research related to maternal opioid use and its effect on the mother and infant.

• Aim 1: Develop and validate electronic health records-based algorithms to identify opioid-exposed infants and their mothers, key covariates (e.g., breastfeeding, rooming-in) and to create linkages to state-wide data systems.

• Aim 2: Test the hypothesis that dyads with prenatal maternal treatment for OUD, compared to dyads with untreated maternal; OUD, have an improved birth outcomes (maternal severe morbidity; infant premature birth), and improved postnatal utilization of recommended services (maternal receipt of postnatal OUD medication infant receipt of recommended infant well visits early intervention services for eligible infants within first the 6 months postpartum.

• Aim 3: Test the hypothesis that dyads with prenatal maternal treatment for OUD, compared to dyads with untreated maternal OUD, have improved dyadic stability at 1-year postpartum including 1) biologic mother retaining custody of the infant and 2) no maternal overdose (ED visit, inpatient admission, death) and to determine if infant treatment modifies these outcomes.

Learn more about our projects and research at the Center for Child Health Policy