R01DA059176

Multimodal analysis of gestational health and placental injury in opioid-affected pregnancies - project summary.

Opioids are medically used for safe pain relief and management. However, illicit opioid use has substantially increased across the US in the past decade, with further worsening during the COVID-19 pandemic, leading to a profound impact on human health.

Specifically, opioid use disorder (OUD) during pregnancy poses an increased risk of pregnancy-associated maternal morbidity and mortality, fetal growth restriction (FGR) and related complications, neonatal opioid withdrawal syndrome, and long-term neurobehavioral effects.

Some of these risks persist despite the use of safer opioids, such as buprenorphine and methadone, medications for OUD (MOUD) patients.

Whereas current studies center mainly on transplacental opioid transport to the fetus and the adverse effects of opioids on infants, the direct impact of illicit and prescription opioids on placental development, differentiation, and function are largely unexplored.

The placental floating villi mediate maternal-fetal gas exchange, nutrient uptake, waste release, immune defense, and the production of hormones and extracellular vesicles (EVS). These villi are covered by a layer of multinucleated, terminally differentiated syncytiotrophoblasts (STBs), which forms the feto-placental frontline that is directly exposed to opioids in the maternal blood.

Subjacent to this layer are mononucleated, progenitor cytotrophoblasts (CTBs), which replenish the STB layer through the process of differentiation and fusion. Importantly, injuries to the STB and CTB layers are implicated in pregnancy-associated complications, including FGR and stillbirth.

Here we seek to investigate opioid-dependent placental injury, focusing on the most critical and unique layer of placental trophoblasts.

We will enroll participants with OUD, including illicit opioids and MOUD (buprenorphine, methadone), examine their pregnancy course and their children's health through the first year postpartum.

Using biospecimens from each participant, including maternal plasma and urine across the three trimesters, placental biopsies, and fetal cord blood at delivery, we will employ multimodal cutting-edge technologies, including single-cell RNAseq, spatial transcriptomics, protein chip cytometry, and placenta EV RNA profiling, and explore the molecular and cellular processes affected by opioids in the maternal-placental-fetal trio-ecosystem.

To gain mechanistic insights into the functional changes in gene expression and EV cargo, we will use an array of model systems, including human trophoblast stem cells and cultured primary human trophoblasts, and mechanistically interrogate pathways underlying opioid injury.

We will further correlate key molecular signatures with clinical assessment, including maternal gestational disorders, perinatal and infant neurodevelopmental outcomes.

Together, our strategic plan, bolstered by our transdisciplinary team, enables us to address critically important knowledge gaps related to human placenta biology in opioid-affected pregnancies.

Children's Research Institute

TO SUPPORT BASIC AND CLINICAL NEUROSCIENCE, BIOMEDICAL, BEHAVIORAL AND SOCIAL SCIENCE, EPIDEMIOLOGIC, HEALTH SERVICES AND HEALTH DISPARITY RESEARCH. TO DEVELOP NEW KNOWLEDGE AND APPROACHES RELATED TO THE PREVENTION, DIAGNOSIS, TREATMENT, ETIOLOGY, AND CONSEQUENCES OF DRUG ABUSE AND ADDICTION, INCLUDING HIV/AIDS. TO SUPPORT RESEARCH TRAINING AND RESEARCH SCIENTIST DEVELOPMENT. TO SUPPORT DISSEMINATION OF RESEARCH FINDINGS. SMALL BUSINESS INNOVATION RESEARCH (SBIR) LEGISLATION IS INTENDED TO EXPAND AND IMPROVE THE SBIR PROGRAMS TO EMPHASIZE AND INCREASE PRIVATE SECTOR COMMERCIALIZATION OF TECHNOLOGY DEVELOPED THROUGH FEDERAL SBIR RESEARCH AND DEVELOPMENT, INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN THE SBIR PROGRAM. THE LEGISLATION INTENDS THAT THE SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.279 - Drug Abuse and Addiction Research Programs

National Institute on Drug Abuse (NIDA) [HHS - NIH]

Washington, District Of Columbia 20010 United States

Single Zip Code

Change of Recipient Organization (Type 7 Parent Clinical Trial Optional) (PA-24-254)

Amendment Since initial award the End Date has been extended from 07/30/26 to 07/31/26 and the total obligations have increased 9% from $3,092,159 to $3,380,800.