NIH – HEAL Initiative: Opioid Exposure and Effects on Placenta Function, Brain Development, and Neurodevelopmental Outcomes (R01 Clinical Trial Not Allowed)

September 9, 2022 by


This Funding Opportunity Announcement (FOA) invites grant applications to study the impact of opioids, alone or in combination with other substances of misuse, on placenta function and neurodevelopment during pregnancy and in the first year of life. Clinical Trials are not permitted for this FOA; researchers proposing Basic Experimental Studies with Humans (BESH) should consider the companion FOA, RFA-HD-23-032, “HEAL Initiative: Opioid Exposure and Effects on Placenta Function, Brain Development, and Neurodevelopmental Outcomes (R01 Basic Experimental Studies with Humans Required)”.


This Funding Opportunity Announcement is part of the NIH’s Helping to End Addiction Long-term (HEAL) initiative to speed scientific solutions to the national opioid public health crisis. The NIH HEAL Initiative bolsters research across NIH to (1) improve treatment for opioid misuse and addiction and (2) enhance pain management. More information about the HEAL Initiative is available at:

In 2020 and 2021, the CDC reported that opioid use occurs in approximately 6% of pregnant people and that opioid-related diagnoses at birth have increased by 131% over the previous decade. These increases in opioid use and exposure to opioids and their illicit analogues alone or in combination with other substances misused during pregnancy—including alcohol, tobacco, and marijuana—may have significant consequences for placenta function and brain development in exposed fetuses.

The placenta is an important endocrine organ that serves several roles. The placenta transfers nutrients, gases and waste products between the mother and fetus and produces hormones that support pregnancy. Additionally, placentation involves remodeling of the uterine spiral arteries to create a supportive vascular environment, prevents immune-mediated rejection of the fetus, and provides protection against infectious agents and noxious environmental insults. A growing literature suggests that environmental inputs to the placenta play a major role in determining the trajectory of placental development and functional sufficiency. Abnormalities of placental development and function underlie many major pathologies of pregnancy and play a role in the development of health issues in affected fetuses during gestation and later in life. Brain development during the fetal, neonatal, and infancy periods reflects a time of considerable growth and plasticity that is also highly susceptible to environmental influences, including maternal substance use, nutrition, and environmental adversity (e.g., economic inequity, neighborhood disadvantage, and stressful life events). Prenatal exposure to opioids has been reported to impact a host of neurocognitive outcomes in early childhood, including but not limited to altered structural and functional connectivity, neurodevelopmental delays, and impaired visual acuity. However, there are few prospective studies that have examined trajectories of disruption due to opioid exposure in brain structure, morphology, and function within the acute period between fetal development and early infancy (i.e., the first year of life).

This funding announcement seeks to utilize human and model-based approaches to understand the impacts of prenatal opioid exposure on brain and placental structure and function, including but not limited to examining molecular, neurocognitive, genetic, and epigenetic mechanisms. The mechanistic understanding of how the maternal-placental-fetal ecosystem and fetal brain development interact in response to opioid use, alone or in concert with other substances, to impact neonatal and infant developmental outcomes remains limited; however, this knowledge is critical to establishing appropriate approaches for prevention and early intervention and establishing clinical guidelines for pain management and substance use and dependance treatment during pregnancy.

Recent advances in technologies provide a rich array of powerful approaches to address longstanding yet fundamental questions of critical importance on the effects of opioid exposure on placental and brain structure and function during early critical periods of development. For example, new imaging technologies have fostered significant advances in our ability to assess placenta development and function across pregnancy and delineate structural and functional trajectories of human brain development during the fetal, neonatal, and early infancy periods.

In addition to imaging approaches, cutting-edge technologies for genetic and genomic analysis, cell-census measurements, and detection of circulating biomarkers such as maternal/fetal/placental circulating cells and miRNA, cytokines, extracellular vesicles, and lipidome are poised for application to further our understanding the effects of opioid exposure and developmental consequences for exposed fetuses. Each of these emerging technologies is showing potential value on their own; it is envisioned that a multimodal approach may provide the most robust approach to assess opioid’s effects on placental and brain development from the fetal through early infancy period.

Key Dates:

Open Date (Earliest Submission Date): November 07, 2022
Letter of Intent Due Date(s): November 08, 2022
Applications Due: December 7, 2022

URL for more information:

Filed Under: Funding Opportunities