Joe Wang, Division of Metabolism and Health Effects

Purpose

The purpose of the proposed FOAs is to solicit applications to continue the Collaborative Initiative on Fetal Alcohol Spectrum Disorders (CIFASD) consortium. CIFASD is an NIAAA-funded initiative conducting Fetal Alcohol Spectrum Disorders (FASD) research through multidisciplinary and collaborative approaches. Applications responsive to these FOAs should address urgent and important issues around diagnosis, intervention, prevention, and biological mechanisms of effect.

Background

Over the last two decades, the FASD research field has seen significant advances in many areas. Our understanding of prenatal alcohol exposure (PAE)-induced brain pathology and associated facial features, especially among diverse populations and across lifespan, has been expanded significantly by new imaging and computing technologies. The range of defects associated with FASD has been better defined at the level of timing, frequency, and amount of PAE; as well as the contribution of genetic and environmental risk factors. Towards intervention development, choline supplementation has shown promise of a lasting benefit for mitigating certain memory deficits when given either to young children or to women during pregnancy.

Despite this progress, challenges remain. Most of these are rooted in the wide range of physical, cognitive, and behavioral deficits and their heterogeneous presentations in individuals with FASD. There is an urgent need for reliable and accurate diagnostic schemes and rapid screening tools. Development of new therapies and interventions that are efficacious in mitigating multiple domains of dysfunction is critical for improving the lives of individuals with FASD. Moreover, given the high prevalence of FASD, there continues to be a need for new and effective FASD prevention strategies.

Scope/Research Objectives

Applications in response to these FOAs should address the urgent and high impact questions of the FASD research around diagnosis, interventions, prevention, and biological mechanisms of effect in diverse populations and across the lifespan. Research in these areas may seek to:

Identify FASD cases early and accurately:

  • Improve the accuracy and reliability of the clinical recognition of FASD above and beyond the existing research and clinical methodologies
  • Improve access to validated screening tools for diverse populations and across the lifespan
  • Explore technologies to improve earlier case identification in neonates and infants

Expand and translate basic and mechanistic understandings of PAE:

  • Investigate the functional significance of molecular targets identified in human samples and validate their clinical significance
  • Understand the full range of structural and functional deficits from PAE
  • Improve our understanding of risk and resiliency factors underlying FASD across the lifespan

Reduce prenatal alcohol exposure and the incidence of FASD:

  • Design innovative approaches to reduce drinking during pregnancy, and in women of childbearing age
  • Develop and/or implement validated tools for alcohol use reduction and expand access

Improve interventions to mitigate FASD outcomes:

Achievements

Over the last 3.5 years, CIFASD4 has made significant advances in most of its research aims with over 70 publications. Among the advances are telemedicine for remote diagnosis, an online screening app based on behavioral tests and facial dysmorphology, an automated system for analyzing facial 2D/3D imaging using smartphones, and a randomized clinical trial of an app-based intervention for families and caregivers of individuals with FASD. Progress in other areas include the translational potential of maternal plasma microRNAs for predicting FASD outcomes in children and the impact of combined cannabinoids and alcohol exposures on birth defects in animal models. As in past iterations of the consortium, these advances are made possible by leveraging both domestic and international cohorts of study subjects in a highly coordinated manner among clinicians, biomedical researchers, and computer scientists.

Justification/Outcome

NIAAA recommends extending support of CIFASD to address the many FASD challenges that remain. Since its inception, the CIFASD consortium has been a highly successful and productive program at NIAAA, for its high impact findings in preclinical-clinical research and nearly 300 publications, a majority of which resulted from multidisciplinary collaborations. CIFASD has also been successful in training of a new generation of FASD researchers in independent and collaborative research.

With significant and promising progress made from CIFASD4, an open competition soliciting new collaborative efforts to tackle important challenges in the FASD field is warranted.

Diversity

The NIAAA-funded consortia are expected to engage diverse group of scientists in biomedical research, which includes but is not limited to participation of individuals from underrepresented backgrounds (i.e. racial and ethnic minorities, persons with disabilities, or persons from disadvantaged backgrounds), women, early-stage and experienced investigators with a track record of funding, and investigators from various disciplines/departments and specialties. NOT OD 20-031 (Notice of NIH's Interest in Diversity).

Grant Mechanism

The CIFASD consortium will be managed by the Administrative Resource core (U24), which will provide the scientific leadership, consortium-wide oversight, and coordination, to the whole consortium. The administrative core will be responsible for managing the Scientific Advisory Board and the research Steering Committee. This component must include a detailed description of the leadership succession plan to ensure that a pipeline of leaders will be available when they are needed, in the event that the Consortium Director becomes incapacitated or for some other reasons, not able to continue as leader of the consortium. The Administrative Core must also lay out a plan on how the next generation of scientists from diverse background would be elevated to leadership positions.

The consortium will also include research resources U24, to provide resources and services to the other components, i.e., UH2 (developmental and exploratory research projects) and U01 research projects. Individual research projects (U01 and UH2) will be expected to address one or more of the research themes outlined above by leveraging the use of national and international FASD cohorts and an integrated collaborative approach.

The proposed RFAs, which will be open to all qualified and eligible applicants, are re-issues of the following:

RFA-AA-17-007, U01 Research Project

RFA-AA-17-008, U24 Administrative Resource Core

RFA-AA-17-009, U24 Dysmorphology Research Resource Core

RFA-AA-17-010, U24 Informatics Research Resource Core

RFA-AA-17-011, U24 Outreach/Dissemination Resource Core

RFA-AA-17-012, UH2 Exploratory/Developmental Research Projects

RFA-AA-20-008, UH2, Exploratory/Developmental Research Projects