Volume 20, Number 1, March 2009
The Collaborative Initiative on Fetal Alcohol Spectrum Disorders (CIFASD) is an NIAAA-funded consortium that is focused on informing and developing diagnostic measures, effective interventions and treatment approaches for prenatal alcohol exposure-induced defects. The structural and functional defects that result from maternal alcohol use com-prise fetal alcohol spectrum disorders (FASD). At the severe end of the spectrum is Fetal Alcohol Syndrome (FAS), a condition characterized and diagnosed by facial dysmorphology, growth retardation and brain damage. Clinical observation first recognized FAS in the 1970s, and currently, there is no doubt that prenatal alcohol exposure can cause FAS in humans and animals. While physical features of FAS identify the severely affected individuals, it is estimated by FAS epidemiology investigators that FAS represents only 25% of FASD, with the latter impacting 3-4 births per 1,000 in the USA. FASD is a problem not only in this country but worldwide. To move the field forward through scientific exchange, basic and clinical CIFASD investigators from across the US, the United Kingdom and South Africa, along with UNC scientists, met recently in Chapel Hill.
The CIFASD multidisciplinary research effort includes animal and human studies that focus on the neuroanatomical and behavioral manifestations of FASD. The collaborative endeavor fosters basic, clinical and translational research on FASD through common goals. Regular meetings of the group not only facilitate exchanges of information but also allow rapid resolution of significance and identify specific areas for additional focus and implementation strategies. Drs. Ed Riley (CIFASD Program Director) and Michael Charness (CIFASD Scientific Director and Bowles External Advisory Board member) with CIFASD member Dr. Kathy Sulik (Bowles Faculty) organized the meeting of CIFASD investigators and invited guests. NIAAA leaders Drs. Kenneth Warren and Dan Hereld, as well as NIAAA Alumnus Dr. Faye Calhoun, contributed their expertise and leadership.
The three days of stimulating scientific exchange began with presentations by two local guests: Drs. Al Johnson, a world leader in magnetic resonance imaging (MRI), and C.J. Malanga, a UNC pediatric neurologist who is initiating novel studies regarding the impact of prenatal alcohol on adult brain reward systems and associated persistent behavioral changes. Dr. Johnson’s talk about new imaging methodologies that allow improved structural and func-tional determinations in both small animal basic science experi-ments as well as in living humans gen-erated considerable excitement. Dr. Malanga’s discovery of marked genetic determinants of prenatal alcohol-mediated disruption of adult reward systems also stimulated much discussion and interest.
From Left to Right: Sarah Mattson, Ph.D., Michael Charness, M.D., Kenneth Warren, Ph.D., Kathy Sulik, Ph.D., Ed Riley, Ph.D., and Fulton Crews , Ph.D.
Presentations by the CIFASD investigators started with Dr. Kathy Sulik. Her studies model early prenatal alcohol exposure in mice. Of particular importance for her work is the use of high resolution MRI, which allows identification of brain damage and concurrent facial dysmorphology (see Figure). This was followed by a presentation by Dr. Elizabeth Sowell (UCLA) whose work utilizes MRI to investigate characteristics of children following exposure to alcohol in utero, allowing translational insights between the Sulik and Sowell MRI studies. Both reports highlighted new findings on brain regions that are affected in FASD. Dr. Ken Jones of the University of California, San Diego (UCSD), one of the physicians to originally describe FAS, continued with a presentation of new studies on morphological diagnostic factors that could be used to identify FASD. This was complimented by descriptions by Feng Zhou and Tatiana Foroud of Indiana University-Purdue University, Indianapolis (IUPUI) of the application of three-dimensional facial imaging to facilitate diagnosis. Tim Cudd (Texas A&M), utilizing a sheep model, is also exploring alcohol-induced facial dysmorphology and presented an update on this work.
Figure (Above): 3-D reconstruction of high resolution magnetic resonance images allows detailed analyses of the faces and brains of fetal mice. As compared to a control fetus whose face is shown in (a) and whose brain is shown in (c; frontal view) and (e; dorsal view), a prenatally alcohol-exposed fetus (b, d, f) has defects involving both its face and brain. Most apparent in the face (b) is the small nose and abnormal upper lip. Both the frontal (d) and dorsal (f) views of the brain illustrate deficiencies primarily involving the forebrain (esp. cerebral hemispheres and olfactory bulbs). Similar examination of the spectrum of defects that results from ethanol exposure at specific developmental stages and comparison to human data, as is emerging from the consortium’s efforts, promises to aid in identifying new FASD diagnostic criteria.
Presentations by two guest scholars from England, Drs. Peter Hammond from University College, London, and Christian Klingenberg from the University of Manchester, highlighted the second day of the meeting. Both focused on state of the art systems for analysis of facial form and applicability for FASD diagnosis. The group discussed how these systems could be used in both human and animal studies.
Important insights were also provided by Dr. Hannah Kinney, a Boston Children’s Hospital-based neuropathologist who is involved in sudden infant death (SIDS) research and is a member of the National Institute on Child Health and Human Development (NICHD) and NIAAA-funded Prenatal Alcohol and SIDS and Stillbirth (PASS) network. The large PASS patient population provides an additional potential study population for CIFASD. Large groups of humans need to be studied in order to understand the full impact of in utero alcohol exposure.
One complication for understanding the full range of abnormality that results from in utero alcohol exposure is that it is common for women not to remember or not want to say that they drank during pregnancy. Biomarkers of alcohol exposure offer a potential solution to this problem. Drs. Charles Goodlett (IUPU; CIFASD investigator) and Dan Savage, University of New Mexico (UNM) and CIFASD steering committee member, gave presentations regarding CIFASD tissue banks and efforts to discover and verify biomarkers of alcohol exposure in tissues such as hair, meconium and placenta.
Discussion of animal and human studies regarding the interaction of nutrition and prenatal alcohol exposure on FASD behaviors made for a lively afternoon. CIFASD Investigators Dr. Jennifer Thomas and Dr. Sarah Mattson (San Diego State University), along with Dr. Christina Chambers (UCSD), gave complementary presentations regarding detailed studies of children exposed to alcohol and how diet during alcohol exposure can affect brain development. Interestingly, supplementation with choline, a key nutrient, is showing promising results in Dr. Thomas’ animal studies. In the UNC Nutrition Department, Dr. Steve Zeisel has for many years studied the benefits of choline for brain development. His group has shown that when rat pups receive choline supplements in utero or during the second week of life, their brain function changes such that there is lifelong memory enhancement.
The focus of the final meeting day was on collection and analyses of data from national and international studies of human alcohol-exposed pregnancies and children. The international sites at which investigations are currently being conducted are in South Africa and Ukraine. Presenting site-specific progress, needs and goals were Dr. Claire Coles (Emory University), Phil May (UNM) and Dr. Colleen Adnams (University of Cape Town). This was followed by discussion of ways in which to best utilize resources and maximize uniformity in data collection and reporting, as well as intra-consortium access to data.
Overall, the meeting set the course for the coming year of studies. Additionally, it provided a wonderful opportunity for Bowles Center faculty to learn about and contribute to the CIFASD.
In mid-March, a number of the CIFASD members, including Bowles Center member Dr. Sulik, presented their findings in Victoria, BC, Canada, at the 3rd International Conference on Fetal Alcohol Spectrum Disorder: Integrated Research, Policy and Promising Practice Around the World: A Catalyst for Change (http://www.interprofessional.ubc.ca/FASD09.htm). The emphasis of this conference was the practical application of various forms of FASD research.
For more information on CIFASD, its news and upcoming events, please visit http://www.cifasd.org.