Funded Projects

NOFO Title: HEAL Initiative: Opioid Exposure and Effects on Placenta Function, Brain Development, and Neurodevelopmental Outcomes (R01 Clinical Trial Not Allowed)
NOFO Number: RFA-HD-23-035
Summary:

Opioid use during pregnancy is associated with significant harmful health outcomes for infants including preterm birth, neonatal opioid withdrawal syndrome, and impaired brain-related problems. This project will combine advanced imaging of the fetal brain and placenta, genetics, and tissue and blood samples from the placenta to determine how opioid use during pregnancy affects development of the fetal brain and placenta. This research will provide novel and early molecular indicators (biomarkers) to as well as identify new strategies for diagnosing, treating, and preventing opioid harm to the fetus and mother.

NOFO Title: Opioid Use Disorder in Pregnancy (R01)
NOFO Number: RFA-HD-18-036
Summary:

Neonatal abstinence syndrome (NAS) rates have increased since 2000. To determine multifactorial genetic, psychosocial predictors of opioid-related maternal and infant outcomes using rigorous prospective longitudinal design, innovative combinatorial pharmacogenetic approach, fetal MRI, and neonatal brain resting state functional MRI analysis, we hypothesize that a combination of maternal and infant genetic profiles, maternal psychosocial factors, maternal opioid treatment response, fetal and neonatal neurodevelopment, and NAS treatment will affect maternal and childhood outcomes with prenatal opioid exposure. The specific aims are to (1) Identify high-risk genetic profiles and psychosocial factors in pregnant women with opioid use disorder (OUD) and predisposing to poor maternal opioid maintenance treatment outcomes; (2) Determine maternal-infant genetic profiles and maternal opioid treatment factors predicting adverse fetal development, severity of NAS, and neonatal brain function; and (3) Develop predictive models for maternal opioid relapse and poor long-term neurodevelopmental outcomes in children with in utero opioid exposure.

NOFO Title: HEAL Initiative: HEALthy Brain and Child Development Study (HEALthy BCD) (R34 Clinical Trial Not Allowed)
NOFO Number: RFA-DA-19-036
Summary:

Researchers will expand a recently initiated pregnancy cohort at Johns Hopkins University (JHU) called ORCHARD (ORigins of Child Health And Resilience in Development) to create a Baltimore HEALthy BCD site, named HEALthy ORCHARD. The research team will convene investigators at JHU and the Kennedy Krieger Institute (KKI), and community partners across nine work groups to: (1) develop protocols for recruitment and retention of pregnant mothers and children with enriched sampling of pregnant women who are using substances; (2) establish community, medical, and government partnerships necessary to implement recruitment, retention, data collection and community benefits; (3) characterize the critical ethical and legal challenges raised during study design, in pilot studies, and by prospective participants, and propose solutions where possible and additional research where necessary; (4) develop protocols for longitudinal data collection across pregnancy and childhood; and (5) contribute to multi-site protocol development and nationally relevant principles regarding ethical and legal issues.

NOFO Title: Opioid Use Disorder in Pregnancy (R01)
NOFO Number: RFA-HD-18-036
Summary:

This study will challenge current clinical approaches to managing the pregnant woman with opioid use disorder. Dosing of buprenorphine (BUP) in pregnant women is based on studies in non-pregnant subjects, which suggests that symptoms of withdrawal occur when plasma BUP concentrations are < 1ng/ml. No such data exist for pregnant women, but this is a prerequisite for defining an appropriate dosing regimen of BUP in pregnant women. We will define this threshold by monitoring women undergoing mild, medically directed withdrawal. The Clinical Opioid Withdrawal Scale score and the Finnegan score for NAS are key to defining when withdrawal occurs and thus dictate treatment in mother and baby. Neither scoring system is based on plasma BUP concentrations and thus, may not reflect true opioid withdrawal. This proposal aims to develop physiologic-based scoring systems that refine the accuracy of diagnosis and optimize treatment.

NOFO Title: HEAL Initiative: Development and validation of virtual assessments to study children and caregivers in their natural environment (R01- Clinical Trial Not Allowed)
NOFO Number: RFA-DA-23-050
Summary:

Use of remote data collection in developmental research can make it easier for families to participate in such research and increase sociodemographic diversity of participants. The goal of this project is to validate remote methods for testing early cognitive development, particularly attention and memory skills, in 4-, 8-, and 12-month-old infants from traditionally underrepresented populations in neuroscience research. The project will integrate multiple types of data to improve remote measurement of infant cognition within the home and will help expand understanding of developmental trajectories and mechanisms across diverse environments and contexts.

NOFO Title: HEAL Initiative: HEALthy Brain and Child Development Study (HEALthy BCD) (Collaborative R34 Clinical Trial Not Allowed)
NOFO Number: RFA-DA-19-029
Summary:

Rates of neonatal abstinence syndrome have reached a staggering 6.5 per 1,000 births nationwide, creating an urgent need to identify how in-utero exposure to opioids and associated risk factors influence the developing brain. A multidisciplinary team will address these challenges in Oregon, a state particularly hard hit by the opioid epidemic. Through linking sites, the impact of the Phase I project is enhanced and will provide critical information to support a national-level effort for Phase II of the HEALthy Brain and Child Development Study. Aim 1 will develop, implement, and evaluate innovative recruitment and retention strategies for high-risk populations. Aim 2 will address anticipated challenges of the planned Phase II study by implementing and evaluating a multi-site, standardized research protocol including multimodal MRI of placenta, fetus, neonate, and 24-month-old brain; biospecimen collection; and assessment of substance use and other key domains. Aim 3 will evaluate data acquisition, processing, and statistical considerations to maximize data quality, usability, and integration across sites.

NOFO Title: HEAL Initiative: HEALthy Brain and Child Development Study (HEALthy BCD) (Collaborative R34 Clinical Trial Not Allowed)
NOFO Number: RFA-DA-19-029
Summary:

Though prenatal exposure to opioids and other substances have adverse effects on neurodevelopment, advances in neuroimaging and developmentally sensitive phenotypic measurement now enable characterization of typical and atypical brain-behavior pathways on an unprecedented scale. The Brains Begin Before Birth (B4) Midwest Consortium, a partnership of neuroscience, substance use, perinatal mental health, and child welfare scientists at Washington University School of Medicine (WUSM) and neuroscience, bioethics, pediatric population health, maternal-fetal, and addiction scientists at Northwestern University (NU). This regional consortium will leverage the contrasting approaches of Illinois (punitive) and Missouri (non-punitive) to prenatal opioid use, providing a platform for examining the impact of jurisdictional variations on science and practice. The consortium provide a framework for addressing three major areas of challenge: (1) legal/ethical, (2) recruitment/retention, and (3) imaging/assessment methods.

NOFO Title: HEAL Initiative: HEALthy Brain and Child Development Study (HEALthy BCD) (Collaborative R34 Clinical Trial Not Allowed)
NOFO Number: RFA-DA-19-029
Summary:

Rates of neonatal abstinence syndrome have reached a staggering 6.5 per 1,000 births nationwide, creating an urgent need to identify how in-utero exposure to opioids and associated risk factors influence the developing brain. A multidisciplinary team will address these challenges in Oregon, a state particularly hard hit by the opioid epidemic. Through linking sites, the impact of the Phase I project is enhanced and will provide critical information to support a national-level effort for Phase II of the HEALthy Brain and Child Development Study. Aim 1 will develop, implement, and evaluate innovative recruitment and retention strategies for high-risk populations. Aim 2 will address anticipated challenges of the planned Phase II study by implementing and evaluating a multi-site, standardized research protocol including multimodal MRI of placenta, fetus, neonate, and 24-month-old brain; biospecimen collection; and assessment of substance use and other key domains. Aim 3 will evaluate data acquisition, processing, and statistical considerations to maximize data quality, usability, and integration across sites.

NOFO Title: HEAL Initiative: HEALthy Brain and Child Development Study (HEALthy BCD) (Collaborative R34 Clinical Trial Not Allowed)
NOFO Number: RFA-DA-19-029
Summary:

The Planning for the HEALthy Early Development Study will contribute to the design and recommended protocol for a future large-scale, multi-site research study to prospectively examine human brain, cognitive, behavioral, social, and emotional development of children beginning prenatally through ages 9–10 and to determine the impact of maternal pre- and postnatal substance use on short- and long-term development of children. The planning study will link investigators across 6 research sites who have complementary experience and expertise in the areas that are essential to designing the study. Planning activities will be accomplished using a coordinated set of 10 working groups. By the end of the planning phase, the 6 consortium sites will have produced and tested a recommended protocol for the future multi-site study and will have established feasibility of carrying out the study protocol at each of the 6 linked sites.

NOFO Title: HEAL Initiative: HEALthy Brain and Child Development Study (Collaborative U01- Clinical Trial Not Allowed)
NOFO Number: RFA-DA-21-020
Summary:

The HEALthy Brain and Child Development National Consortium (HBCD-NC) will establish a normative model of developmental trajectories over the first 10 years of life. All sites in the HBCD-NC will carry out a common research protocol and will assemble and distribute a comprehensive research dataset to the scientific community. The HBCD-NC will collect neural, behavioral, physiological, and psychological measures, as well as biospecimens, to characterize neurodevelopmental trajectories. Most participants will be recruited in the second trimester of pregnancy, with a smaller subset recruited at birth, and followed for the first 10 years of life. The Pennsylvania State University study site is in a region hard hit by opioid and methamphetamine use disorders and will recruit mother-infant pairs from largely rural communities.

NOFO Title: HEAL Initiative: Notice of Special Interest (NOSI) regarding the Availability of Administrative Supplements to Support Strategies to Increase Participant Diversity, Inclusion and Engagement in Clinical Studies
NOFO Number: NOT-NS-21-025
Summary:

The ACT NOW Outcomes of Babies with Opioid Exposure (OBOE) Study – also called the ACT NOW Longitudinal Study – is a longitudinal cohort study to prospectively examine longitudinal outcomes from birth to 2 years of age among infants who were exposed to opioids in utero as compared to matched controls. The objectives of this study are to i) determine the impact of pre-birth opioid exposure on brain structure and connectivity over the first 2 years of life, ii) define medical, developmental, and behavioral outcomes over the first 2 years of life in infants exposed to opioids, and iii) Explore whether and how the home environment, maternal mental health, and parenting affect brain connectivity and neurodevelopment trajectories over the first 2 years of life. This research will use an innovative approach to engage a more diverse study population and thereby improve the generalizability of the research findings.

NOFO Number: PA-18-591
Summary:

Neonatal opioid withdrawal syndrome (NOWS) has emerged as a tragic by-product of the opioid epidemic. Newborns whose mothers used opioids while pregnant can experience symptoms of opioid withdrawal in the days following birth, such as tremors, irritability, seizures, sleep, digestive, and feeding problems. However, little is known about the effect of antenatal opioid exposure on longer-term infant development over time. To address this gap in understanding, the ACT NOW Longitudinal study is examining a crucial developmental period from birth to two years of life through a comprehensive battery of assessments, including MRI imaging, neurodevelopmental behavioral assessments, and family report measures. This longitudinal cohort study is projected to include a total of 375 infants, 250 who were exposed to opioids and 125 matched controls.

NOFO Title:
NOFO Number: PA-20-272