Funded Projects

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Project # Project Title Research Focus Area Research Program Administering IC Sort descending Institution(s) Investigator(s) Location(s) Year Awarded
1R01HD113143-01
Association of Maternal, Fetal, and Placental Biomarkers with Neonatal Neuroimaging and Development Following In-Utero Opioid Exposure Enhanced Outcomes for Infants and Children Exposed to Opioids The Biology of Opioid Exposure During Pregnancy and Effects on Early Neuro-Behavioral Development NICHD BOSTON MEDICAL CENTER WACHMAN, ELISHA Boston, MA 2023
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-23-032
Summary:

Exposure of the developing fetus to opioids during pregnancy in women with opioid use disorder can lead to inefficient placenta function and impaired fetal brain development and neurodevelopmental outcomes. This project will measure molecules that circulate within maternal blood to identify specific indicators (biomarkers) of maternal health such as inflammation and changes in placental gene activity. The research will include a focus on specialized molecules released from the placenta called exosomes that carry information about the health of the placenta. These data will be combined with neurodevelopmental measures of infants at 1 year of age. Together, these studies will provide new molecular predictors (biomarkers) of placenta and fetal health.

1R01HD096798-01
SAFETY, PHARMACOKINETICS AND EFFICACY OF EXTENDED-RELEASE NALTREXONE IN PREGNANT WOMEN WITH OPIOID USE DISORDER Enhanced Outcomes for Infants and Children Exposed to Opioids NICHD Boston Medical Center WACHMAN, ELISHA Boston, MA 2018
NOFO Title: Opioid Use Disorder in Pregnancy (R01)
NOFO Number: RFA-HD-18-036
Summary:

Opioid use disorders (OUDs) in pregnancy are a U.S. public health crisis; the current standard of care is treatment with an opioid agonist such as buprenorphine (BPH), which has an associated risk for neonatal abstinence syndrome (NAS) and possible long-term neurodevelopmental consequences. As a novel treatment option for OUD in pregnancy, naltrexone would not expose the developing fetus to opioids, greatly reducing the risk for NAS and potentially improving maternal and infant outcomes. This study will evaluate the safety, efficacy, pharmacokinetics, and pharmacogenomics of naltrexone for pregnant women with OUDs, evaluating comprehensive mother-infant outcomes throughout the pregnancy and first year after birth. It will enroll 50 pregnant women stabilized pre-pregnancy on extended-release naltrexone (XR-NTX) and 50 comparison women on BPH from Boston Medical Center and the University of North Carolina in this multi-center prospective comparative cohort study.

1PL1HD101059-01
HEAL Initiative: Antenatal Opioid Exposure Longitudinal Study Consortium Enhanced Outcomes for Infants and Children Exposed to Opioids Advancing Clinical Trials in Neonatal Opioid Withdrawal (ACT NOW) NICHD RESEARCH TRIANGLE INSTITUTE BANN, CARLA M Research Triangle Park, NC 2019
NOFO Title: HEAL Initiative: Antenatal Opioid Exposure Longitudinal Study Consortium (PL1 Clinical Trial Not Allowed)
NOFO Number: RFA-HD-19-025
Summary:

The incidence of Neonatal Opioid Withdrawal Syndrome (NOWS) in the United States has increased more than fivefold since 2004 to almost 7 per 1,000 hospital births. It is unknown how these effects are modulated by associated maternal, neonatal, and environmental factors and how the environment, maternal health, and parenting styles modify trajectories of brain connectivity and neurodevelopment. This study leverages the established infrastructure and longstanding collaborations of four clinical sites and the data coordinating center of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network to address current critical knowledge gaps in childhood brain structure and connectivity and on medical, developmental, and behavioral trajectories in early childhood. The study will analyze a well-characterized observational cohort using clinical and neuroimaging measures to improve understanding of the structural and functional sequelae resulting from prenatal opioid exposure and NOWS and their interactions with the maternal-infant dyad.

1U24HD107621-01
Data Coordinating Center (DCC) for the Neonatal Opioid Withdrawal Syndrome Pharmacological Treatments Comparative Effectiveness Trial (NOWS PhaCET) Enhanced Outcomes for Infants and Children Exposed to Opioids Advancing Clinical Trials in Neonatal Opioid Withdrawal (ACT NOW) NICHD RESEARCH TRIANGLE INSTITUTE (NC) DAS, ABHIK Research Triangle Park, NC 2021
NOFO Title: HEAL Initiative: Data Coordinating Center for the Neonatal Opioid Withdrawal Syndrome Pharmacological Treatments Comparative Effectiveness Trial (U24 Clinical Trial Required)
NOFO Number: RFA-HD-21-032
Summary:

Neonatal Opioid Withdrawal Syndrome (NOWS) is a condition that occurs when newborns are exposed to opioids during pregnancy. Symptoms often include tremors, excessive crying, sleep deprivation, and swallowing difficulties. Cases are rising, with a newborn affected by NOWS approximately every 15 minutes. Currently, healthcare providers in the United States lack standard, evidence-based treatments for NOWS. 

This project is part of a multi-center, randomized controlled clinical trial that directly compares NOWS treatments—morphine, methadone, and buprenorphine—and takes into account other types of non-drug therapies, such as behavioral interventions. The goal is to generate results that can inform clinical practice guidelines and give newborns with NOWS the best start possible. 

This site will serve as the Data Coordinating Center for the clinical trial to provide high-quality and impartial biostatistical expertise for all the study sites.

1UG1HD107580-01
UAB Clinical Site HEAL Neonatal Opioid Withdrawal Pharmacological Treatments Enhanced Outcomes for Infants and Children Exposed to Opioids Advancing Clinical Trials in Neonatal Opioid Withdrawal (ACT NOW) NICHD UNIVERSITY OF ALABAMA AT BIRMINGHAM  (AL) AMBALAVANAN, NAMASIVAYAM   Birmingham, AL 2021
NOFO Title: HEAL Initiative: Neonatal Opioid Withdrawal Syndrome Pharmacological Treatments Comparative Effectiveness Trial - Clinical Sites (UG1 Clinical Trial Required)
NOFO Number: RFA-HD-21-031
Summary:

Neonatal Opioid Withdrawal Syndrome (NOWS) is a condition that occurs when newborns are exposed to opioids during pregnancy. Symptoms often include tremors, excessive crying, sleep deprivation, and swallowing difficulties. Cases are rising, with a newborn affected by NOWS approximately every 15 minutes. Currently, healthcare providers in the United States lack standard, evidence-based treatments for NOWS. 

This project is part of a multi-center, randomized controlled clinical trial that directly compares NOWS treatments—morphine, methadone, and buprenorphine—and takes into account other types of non-drug therapies, such as behavioral interventions. The goal is to generate results that can inform clinical practice guidelines and give newborns with NOWS the best start possible. 

The University of Alabama at Birmingham routinely treats newborns with NOWS and has been part of NICHD’s Neonatal Research Network (NRN) for more than 25 years. The center has an excellent track record of enrollment in clinical studies, with successful follow-up to 2 years of age and beyond.

1R01HD096796-01
PHARMACOLOGICALLY-BASED STRATEGIES FOR BUPRENORPHINE TREATMENT DURING PREGNANCY Enhanced Outcomes for Infants and Children Exposed to Opioids NICHD Magee-Women's Research Institute and Foundation CARITIS, STEVE N Pittsburgh, PA 2018
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.

1UG1HD107650-01
HEAL Initiative: Neonatal Opioid Withdrawal Syndrome Pharmacological Treatments Comparative Effectiveness Trial Clinical Site Enhanced Outcomes for Infants and Children Exposed to Opioids Advancing Clinical Trials in Neonatal Opioid Withdrawal (ACT NOW) NICHD UNIV OF ARKANSAS FOR MED SCIS  (AR) HALL, RICHARD WHITTINGTON  Little Rock, AR 2021
NOFO Title: HEAL Initiative: Neonatal Opioid Withdrawal Syndrome Pharmacological Treatments Comparative Effectiveness Trial - Clinical Sites (UG1 Clinical Trial Required)
NOFO Number: RFA-HD-21-031
Summary:

Neonatal Opioid Withdrawal Syndrome (NOWS) is a condition that occurs when newborns are exposed to opioids during pregnancy. Symptoms often include tremors, excessive crying, sleep deprivation, and swallowing difficulties. Cases are rising, with a newborn affected by NOWS approximately every 15 minutes. Currently, healthcare providers in the United States lack standard, evidence-based treatments for NOWS. 

This project is part of a multi-center, randomized controlled clinical trial that directly compares NOWS treatments—morphine, methadone, and buprenorphine—and takes into account other types of non-drug therapies, such as behavioral interventions. The goal is to generate results that can inform clinical practice guidelines and give newborns with NOWS the best start possible. 

Arkansas is a rural state with the second highest opioid prescription rate in the nation and is in the top 3 states nationwide for opioid prescriptions to pregnant mothers. This site has extensive experience in opioid research and conducting multi-center clinical trials. It also provides care to a diverse population.

3PL1HD101059-01S1
Supplement to increase the sample size of the Outcomes of Babies with Opioid Exposure (OBOE) study cohort. Enhanced Outcomes for Infants and Children Exposed to Opioids Advancing Clinical Trials in Neonatal Opioid Withdrawal (ACT NOW) NICHD Research Triangle Institute Bann, Carla Research Triangle Park, NC 2020
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.

1UG1HD107628-01
Thomas Jefferson University Hospital Clinical Site for HEAL NOWS Pharmacologic Trial Enhanced Outcomes for Infants and Children Exposed to Opioids Advancing Clinical Trials in Neonatal Opioid Withdrawal (ACT NOW) NICHD THOMAS JEFFERSON UNIVERSITY  (PA) KRAFT, WALTER K (contact); ADENIYI-JONES, SUSAN Philadelphia, PA 2021
NOFO Title: HEAL Initiative: Neonatal Opioid Withdrawal Syndrome Pharmacological Treatments Comparative Effectiveness Trial - Clinical Sites (UG1 Clinical Trial Required)
NOFO Number: RFA-HD-21-031
Summary:

Neonatal Opioid Withdrawal Syndrome (NOWS) is a condition that occurs when newborns are exposed to opioids during pregnancy. Symptoms often include tremors, excessive crying, sleep deprivation, and swallowing difficulties. Cases are rising, with a newborn affected by NOWS approximately every 15 minutes. Currently, healthcare providers in the United States lack standard, evidence-based treatments for NOWS. 

This project is part of a multi-center, randomized controlled clinical trial that directly compares NOWS treatments—morphine, methadone, and buprenorphine—and takes into account other types of non-drug therapies, such as behavioral interventions. The goal is to generate results that can inform clinical practice guidelines and give newborns with NOWS the best start possible. 

Thomas Jefferson University has more than 40 years of experience optimizing approaches to the care of opioid use disorder in pregnancy and conducts clinical research on NOWS treatments. The hospital provides a robust continuum of care that supports women with opioid use disorders before, during, and after delivery. This supportive culture has resulted in a relatively high rate of clinical trial participation that will enable long-term follow up of mothers and infants.

1R01HD113032-01
Predicting Neonatal Health Outcomes From Placental and Fetal Brain Extracellular Vesicles in Pregnant Opioid Users Enhanced Outcomes for Infants and Children Exposed to Opioids The Biology of Opioid Exposure During Pregnancy and Effects on Early Neuro-Behavioral Development NICHD UNIVERSITY OF WASHINGTON VOJTECH, LUCIA N (contact); CHIU, DANIEL T Seattle,WA 2023
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-23-037
Summary:

Opioid use during pregnancy is associated with significant harmful health outcomes for infants including preterm birth, neonatal opioid withdrawal syndrome (NOWS), and impaired brain-related problems. Not all infants exposed to opioids develop NOWS, and there is a need for better diagnostic tests. This project will study specialized cell structures called vesicles that are released from the placenta, fetal brain, and central nervous system to communicate information about health of the fetus and placenta. This research on vesicles will be combined with data about NOWS diagnosis up to 1 month after birth. The research aims to generate molecular indicators (biomarkers) that predict which newborns develop NOWS, toward guiding safe and effective treatment for these newborns.

3U24HD095254-03S1
DATA COORDINATING CENTER FOR THE NICHD NEONATAL RESEARCH NETWORK (U24) Enhanced Outcomes for Infants and Children Exposed to Opioids Advancing Clinical Trials in Neonatal Opioid Withdrawal (ACT NOW) NICHD Research Triangle Institute Abhik Das Research Triangle Park, NC 2020
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.

1UG1HD107627-01
HEAL Initiative: Neonatal Opioid Withdrawal Syndrome Pharmacological Treatments Comparative Effectiveness Trial New Mexico Site Enhanced Outcomes for Infants and Children Exposed to Opioids Advancing Clinical Trials in Neonatal Opioid Withdrawal (ACT NOW) NICHD UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR  (NM) LEEMAN, LAWRENCE M Albuquerque, NM 2021
NOFO Title: HEAL Initiative: Neonatal Opioid Withdrawal Syndrome Pharmacological Treatments Comparative Effectiveness Trial - Clinical Sites (UG1 Clinical Trial Required)
NOFO Number: RFA-HD-21-031
Summary:

Neonatal Opioid Withdrawal Syndrome (NOWS) is a condition that occurs when newborns are exposed to opioids during pregnancy. Symptoms often include tremors, excessive crying, sleep deprivation, and swallowing difficulties. Cases are rising, with a newborn affected by NOWS approximately every 15 minutes. Currently, healthcare providers in the United States lack standard, evidence-based treatments for NOWS. 

This project is part of a multi-center, randomized controlled clinical trial that directly compares NOWS treatments—morphine, methadone, and buprenorphine—and takes into account other types of non-drug therapies, such as behavioral interventions. The goal is to generate results that can inform clinical practice guidelines and give newborns with NOWS the best start possible. 

New Mexico is an epicenter of the opioid epidemic with high rates of maternal opioid use disorder and NOWS. This site has expertise in multi-center clinical trials for newborns, a history of high rates of study recruitment and follow-up, and a diverse population that includes Latinx and Native American women. The hospital currently cares for infants with NOWS in a variety of settings, including rooming in, a nursery, and a neonatal intensive care unit.

1UG1HD107631-01
Neonatal Treatment Trial Enhanced Outcomes for Infants and Children Exposed to Opioids Advancing Clinical Trials in Neonatal Opioid Withdrawal (ACT NOW) NICHD CHILDREN'S HOSP OF PHILADELPHIA  (PA) LORCH, SCOTT A  Philadelphia, PA 2021
NOFO Title: HEAL Initiative: Neonatal Opioid Withdrawal Syndrome Pharmacological Treatments Comparative Effectiveness Trial - Clinical Sites (UG1 Clinical Trial Required)
NOFO Number: RFA-HD-21-031
Summary:

Neonatal Opioid Withdrawal Syndrome (NOWS) is a condition that occurs when newborns are exposed to opioids during pregnancy. Symptoms often include tremors, excessive crying, sleep deprivation, and swallowing difficulties. Cases are rising, with a newborn affected by NOWS approximately every 15 minutes. Currently, healthcare providers in the United States lack standard, evidence-based treatments for NOWS. 

This project is part of a multi-center, randomized controlled clinical trial that directly compares NOWS treatments—morphine, methadone, and buprenorphine—and takes into account other types of non-drug therapies, such as behavioral interventions. The goal is to generate results that can inform clinical practice guidelines and give newborns with NOWS the best start possible. 

This site includes newborn nurseries and intensive care nurseries at 4 large
maternity centers across the Children’s Hospital of Philadelphia (CHOP) Newborn Care Network, each with a dedicated follow-up clinic, ensuring access to a large and diverse patient population for long-term study. CHOP also has a long history of successfully conducting multi-center clinical studies.

5U24HD095254-02
ACT NOW Clinical Trials: ESC and Weaning Protocols Enhanced Outcomes for Infants and Children Exposed to Opioids Advancing Clinical Trials in Neonatal Opioid Withdrawal (ACT NOW) NICHD RESEARCH TRIANGLE INSTITUTE Das, Abhik Research Triangle Park, NC 2019
NOFO Title: Data Coordinating Center for the NICHD Neonatal Research Network (U24)
NOFO Number: RFA-HD-18-010
Summary:

The ACT NOW Eat, Sleep, Console (ESC) Clinical Trial approach to the management of neonatal opioid withdrawal syndrome (NOWS) emphasizes parental involvement, simplifies the assessment of infants with NOWS and focuses interventions on non-pharmacologic therapies. Although outcomes following implementation of the ESC care approach, inclusive of the ESC Care Tool, appear promising and initial accounts suggest that it is safe, there has yet to be a rigorous randomized clinical trial to demonstrate the safety, efficacy and generalizability of its use in the care of infants with NOWS. The ESC Clinical Trial leverages the infrastructure and collaborations of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network and the IDeA States Pediatric Clinical Trials Network to reach the populations most affected by the opioid epidemic. The trial will provide answers to numerous critical gaps in our knowledge with respect to the best practices for the identification and management of infants with NOWS, as well as our understanding of the outcomes of these infants.

1UG1HD107616-01
HEAL Initiative: Neonatal Opioid Withdrawal Syndrome Pharmacological Treatments Comparative Effectiveness Trial: Cincinnati Site Enhanced Outcomes for Infants and Children Exposed to Opioids Advancing Clinical Trials in Neonatal Opioid Withdrawal (ACT NOW) NICHD CINCINNATI CHILDRENS HOSP MED CTR  (OH) MERHAR, STEPHANIE L Cincinnati, OH 2021
NOFO Title: HEAL Initiative: Neonatal Opioid Withdrawal Syndrome Pharmacological Treatments Comparative Effectiveness Trial - Clinical Sites (UG1 Clinical Trial Required)
NOFO Number: RFA-HD-21-031
Summary:

Neonatal Opioid Withdrawal Syndrome (NOWS) is a condition that occurs when newborns are exposed to opioids during pregnancy. Symptoms often include tremors, excessive crying, sleep deprivation, and swallowing difficulties. Cases are rising, with a newborn affected by NOWS approximately every 15 minutes. Currently, healthcare providers in the United States lack standard, evidence-based treatments for NOWS. 

This project is part of a multi-center, randomized controlled clinical trial that directly compares NOWS treatments—morphine, methadone, and buprenorphine—and takes into account other types of non-drug therapies, such as behavioral interventions. The goal is to generate results that can inform clinical practice guidelines and give newborns with NOWS the best start possible. 

Ohio and Kentucky have high rates of opioid-related overdose deaths in the nation. This site is a large regional perinatal center, providing clinical services for approximately 25,000 newborns each year. It also actively participates in other HEAL Initiative studies.

1UG1HD107649-01
Neonatal Opioid Withdrawal Syndrome (NOWS) in Kentucky: Improving Outcomes for Infants Enhanced Outcomes for Infants and Children Exposed to Opioids Advancing Clinical Trials in Neonatal Opioid Withdrawal (ACT NOW) NICHD UNIVERSITY OF LOUISVILLE  (KY) DEVLIN-PHINNEY, LORI ANN (contact); TELANG, SUCHETA Louisville, KY 2021
NOFO Title: HEAL Initiative: Neonatal Opioid Withdrawal Syndrome Pharmacological Treatments Comparative Effectiveness Trial - Clinical Sites (UG1 Clinical Trial Required)
NOFO Number: RFA-HD-21-031
Summary:

Neonatal Opioid Withdrawal Syndrome (NOWS) is a condition that occurs when newborns are exposed to opioids during pregnancy. Symptoms often include tremors, excessive crying, sleep deprivation, and swallowing difficulties. Cases are rising, with a newborn affected by NOWS approximately every 15 minutes. Currently, healthcare providers in the United States lack standard, evidence-based treatments for NOWS. 

This project is part of a multi-center, randomized controlled clinical trial that directly compares NOWS treatments—morphine, methadone, and buprenorphine—and takes into account other types of non-drug therapies, such as behavioral interventions. The goal is to generate results that can inform clinical practice guidelines and give newborns with NOWS the best start possible. 

The University of Louisville serves a large, diverse population that is disproportionately affected by the opioid crisis. Mothers and infants treated by the university’s healthcare team live in rural
and urban underserved regions where the frequency of opioid use during pregnancy is among the highest in the country, with a rate estimated at 3 times the national average.

1UG1HD107653-01
Incorporating nonpharmacologic approaches into a comparative effectiveness pharmacologic trial for neonates with neonatal opioid withdrawal syndrome (NOWS) Enhanced Outcomes for Infants and Children Exposed to Opioids Advancing Clinical Trials in Neonatal Opioid Withdrawal (ACT NOW) NICHD INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS (IN) SOKOL, GREGORY M Indianapolis, IN 2021
NOFO Title: HEAL Initiative: Neonatal Opioid Withdrawal Syndrome Pharmacological Treatments Comparative Effectiveness Trial - Clinical Sites (UG1 Clinical Trial Required)
NOFO Number: RFA-HD-21-031
Summary:

Neonatal Opioid Withdrawal Syndrome (NOWS) is a condition that occurs when newborns are exposed to opioids during pregnancy. Symptoms often include tremors, excessive crying, sleep deprivation, and swallowing difficulties. Cases are rising, with a newborn affected by NOWS approximately every 15 minutes. Currently, healthcare providers in the United States lack standard, evidence-based treatments for NOWS.

1R01HD096800-01
EFFECTS OF OPIOID USE DISORDER IN PREGNANCY ON LONG-TERM MATERNAL AND CHILD OUTCOMES Enhanced Outcomes for Infants and Children Exposed to Opioids NICHD Indiana University - Purdue University Indianapolis SADHASIVAM, SENTHILKUMAR Indianapolis, IN 2018
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.

3PL1HD101059-01S2
Administrative Supplement to Increase Participant Diversity, Inclusion and Engagement in the ACT NOW OBOE Study Enhanced Outcomes for Infants and Children Exposed to Opioids Advancing Clinical Trials in Neonatal Opioid Withdrawal (ACT NOW) NICHD RESEARCH TRIANGLE INSTITUTE BANN, CARLA M Research Triangle Park, NC 2021
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.

3PL1HD101059-01S3
Administrative Supplement for ACT NOW OBOE Longitudinal Study Enhanced Outcomes for Infants and Children Exposed to Opioids Advancing Clinical Trials in Neonatal Opioid Withdrawal (ACT NOW) NICHD RESEARCH TRIANGLE INSTITUTE (NC) BANN, CARLA M Research Triangle Park, NC 2021
NOFO Title:
NOFO Number: PA-20-272
1R01HD113199-01
The Opioid in Pregnancy: Imaging of Oxygenation, Inflammation, and Development in Brain & Placenta Project (OPIOID BPP) Enhanced Outcomes for Infants and Children Exposed to Opioids The Biology of Opioid Exposure During Pregnancy and Effects on Early Neuro-Behavioral Development NICHD WASHINGTON UNIVERSITY KELLY, JEANNIE CHEN (contact); WANG, YONG Saint Louis, MO 2023
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-23-030
Summary:

Opioid use disorder during pregnancy is associated with poor infant outcomes including neonatal opioid withdrawal syndrome (NOWS) and impaired brain development during childhood. This project will use advanced imaging techniques to measure inflammation in the placenta and evaluate brain structure of the developing fetus. These data will be combined with measures of infant NOWS and neurodevelopmental outcomes at birth and 1 year of age. This research will explore the value of these imaging methods as diagnostic tools for infants exposed to opioids during pregnancy. The research will also study the effect of opioids on the placenta’s ability to provide oxygen to the growing fetus as well as the potential for inflammation to damage the placenta and harm development of the fetal brain. 

1R01HD113188-01
Impact of Maternal Substance Use on Offspring Neurobehavioral Development Enhanced Outcomes for Infants and Children Exposed to Opioids The Biology of Opioid Exposure During Pregnancy and Effects on Early Neuro-Behavioral Development NICHD MASSACHUSETTS GENERAL HOSPITAL EDLOW, ANDREA GOLDBERG (contact); BOGDAN, RYAN H; LO, JAMIE ; SULLIVAN, ELINOR L Boston, MA 2023
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-23-031
Summary:

Opioid use disorder with simultaneous misuse of cannabis and alcohol during pregnancy is associated with increased risk for several infant neurodevelopmental problems. This project will evaluate the effects of opioids and other substances of misuse on the mother’s immune system by studying maternal immune cells and measuring molecules in her blood. The research will also study the role of the nerve communication molecule serotonin produced by the placenta. This research will take advantage of data from the HEALthy Brain and Child Development Study that is focused on child development measures. Together, these studies will provide important new insights into the ways misused substances affect infant brain development and neurodevelopmental outcomes.

1R34DA050254-01
Biological and Environmental Contributions to Healthy Baby Development in Diverse Population Enhanced Outcomes for Infants and Children Exposed to Opioids HEALthy Brain and Child Development Study (HBCD) NIDA CHILDREN'S HOSPITAL OF LOS ANGELES LEVITT, PAT Los Angeles, CA 2019
NOFO Title: HEAL Initiative: HEALthy Brain and Child Development Study (HEALthy BCD) (R34 Clinical Trial Not Allowed)
NOFO Number: RFA-DA-19-036
Summary:

This project will support consortium hypothesis generation in Phase II in order to disentangle how complex environmental factors impact brain development and function — from fetal period through the first decade — to shape cognitive, social, and emotional development. The project will develop the strategies to recruit and retain a racially and ethnically diverse sample of pregnant women (and their fetuses), who are oversampled for adverse environmental risk factors and exposure to substances of abuse; develop the strategies for managing potential legal and ethical challenges to ensure that the mother–child dyads have access to legal, social, and psychological support services as needed; and determine the optimal study protocol for the planned, phase II study — balancing the need for high quality, longitudinal data collection with the need to minimize burden on the mother–child dyads.

1R34DA050268-01
4/5 Establishing Innovative Approaches for the HEALthy Brain and Child Development Study Enhanced Outcomes for Infants and Children Exposed to Opioids HEALthy Brain and Child Development Study (HBCD) NIDA CINCINNATI CHILDRENS HOSP MED CTR MERHAR, STEPHANIE L (contact); VANNEST, JENNIFER J Cincinnati, OH 2019
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:

A more than 5-fold increase in the incidence of neonatal abstinence syndrome has been reported since 2000. Preliminary studies show that prenatal opioid exposure is associated with increased risk of impaired neurodevelopment. Five institutions (Duke University, Arkansas Children’s Research Institute, Cincinnati Children’s Hospital, University of Illinois at Urbana–Champaign, and University of North Carolina at Chapel Hill) have formed a consortium to develop strategies for the Phase II HEALthy Brain and Child Development Study. Research teams will develop instruments and strategies (recruitment/retention protocols, assessment batteries, and novel tools); conduct pilot studies (fetal and postnatal imaging, advanced imaging harmonization and quality control, assessment administration, biosampling) to evaluate instruments; and analyze available data, including imaging, behavioral, cognitive, and maternal data from studies on early brain development, to guide the Phase II study design. Upon completion, the consortium aims to conduct the Phase II study.

1R01DA059423-01
Automated Assessment of Maternal Sensitivity to Infant Distress: Leveraging Wearable Sensors for Substance Use Disorder Prevention and Research Enhanced Outcomes for Infants and Children Exposed to Opioids Virtual Assessments to Understand Developmental Trajectories of Substance Use Exposure NIDA UNIVERSITY OF TEXAS AT AUSTIN DE BARBARO, KAYA Austin, TX 2023
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:

High-quality parent-infant interactions set the stage for secure parent-child attachment, self-reliance, and children’s ability to flexibly solve problems and “bounce back” from difficulties. This constellation of behaviors reduces the risk of developing substance use disorders later in life. This project will develop algorithms that use data from wearable sensors, trained separately for English- and Spanish-speaking families, to assess the quality of early mother-infant interactions objectively, automatically, and remotely in natural home environments, with the goal of developing tools to facilitate identification and prevention of early risks for substance use disorders.