Early alcohol exposure elicited classic FAS facial features, including
characteristic abnormalities of the upper lip and eyes.
However, mice fetuses exposed just 36 hours later, exhibited unique and in some cases
opposing facial patterns, such as shortened upper lip, and the brain,instead of
appearing too narrow in the front, appeared wide.
Imaging Study Sheds New Light on Alcohol-Related Birth Defects
An international collaborative research effort sheds new light on alcohol-related birth defects, and relates the timing of alcohol exposure to specific birth defects
The project, led by Kathleen K. Sulik, PhD, a professor in the Department of Cell and Developmental Biology and the Bowles Center for Alcohol Studies at UNC, in collaoration with the University College of London in the UK, could help enhance how doctors diagnose birth defects caused by alcohol exposure in the womb.
The findings also illustrate how the precise timing of that exposure can determine specific kinds of defects.
"We now know that maternal alcohol use
is the leading known and preventable
cause of birth defects and mental disability
in the United States.
Alcohol's effects can cause a range
of cognitive, developmental and behavioral problems
that typically become evident during childhood,
and last a lifetime."
Kathleen K. Sulik, Professor, UNC
Fetal alcohol syndrome (FAS) is at the severe end of fetal alcohol spectrum disorders (FASD). First described in 1972, FAS is recognized by a specific pattern of facial features: small eyelid openings, a smooth ridge on the upper lip (absence of a central groove, or philtrum), and a thin upper lip border.
In its full-blown state, FAS affects roughly 1 in 750 live births in the U.S.
While clinicians typically look for those classical facial features in making a diagnosis, within the broader classification of FASD "adverse outcomes vary considerably and most individuals don't exhibit the facial characteristics that currently define FAS," said the study's lead author Robert J. Lipinski, PhD, a postdoctoral scientist in Sulik's lab. "This study could expand the base of diagnostic criteria used by clinicians who suspect problems caused by maternal alcohol use."
In their animal-based studies, the Sulik lab team has collaborated with co-author G. Allan Johnson, PhD and his group at Duke University's Center for In Vivo Microscopy. Johnson, professor of radiology and physics, has developed new imaging tools with spatial resolution up to a million times higher than clinical magnetic resonance imaging (MRI). These include small bore tools suitable for imaging fetal mice that are only 15 mm long.
To quantify facial shape from MRI data, the study team turned to co-author Peter Hammond, a professor of computational biology at UCL's Institute of Child Health, in London. Hammond invented powerful new techniques for 3D shape analysis that have already proven successful in objectively defining facial shape changes in humans.
In the study, described in the August 22, 2012 issue of the online journal PLOS ONE, Lipinski and Sulik treated one group of mice with alcohol on their seventh day of pregnancy, a time corresponding to the third week of pregnancy in humans.
A second group of mice was treated just 36 hours later, approximating the fourth week of human pregnancy. The amount of alcohol given was large, "high doses that most women wouldn't achieve unless they were alcoholic and had a tolerance for alcohol," Sulik said.
Near the end of pregnancy, the fetuses were then imaged at Duke University. These 3D data sets showed individual brain regions, as well as accurate and detailed facial surfaces, from which Hammond and research assistant and co-author Michael Suttie performed shape analyses.
The team found that the earlier alcohol exposure
elicited the classic FAS facial features,
including characteristic abnormalities
of the upper lip and eyes.
What they observed in fetuses exposed
just 36 hours later, however, was a surprise.
These mice exhibited unique and in some cases
opposing facial patterns, such as shortened upper lip,
a present philtrum, and the brain,
instead of appearing too narrow in the front,
Sulik "Overall, the results of our studies show that alcohol can cause more than one pattern of birth defects, and that the type and extent of brain abnormalitieswhich are the most devastating manifestation of prenatal alcohol exposurein some cases may be predicted by specific facial features."
alcohol can cause tremendously devastating
and permanent damage at a time in development
when most women don't recognize
that they're pregnant."
Kathleen K. Sulik, Professor, UNC
Co-authors include Shonagh O'Leary-Moore, Jacob J. Ament, Stephen J. Pecevich, Scott E. Parnell, Elizabeth A. Godin, Joshua L. Everson, Deborah B. Dehart, and Hunter T. Holloway of the UNC Bowles Center for Alcohol Studies; Francois Budin, Ipek Oguz, Martin A. Styner of the UNC department of psychiatry; and Yi Jiang of the Duke University Center for In Vivo Microscopy.
The project was supported by the National Institute of Alcoholism and Alcohol Abuse, the National Institute of Biomedical Imaging and Bioengineering and was conducted in conjunction with the Collaborative Initiative on Fetal Alcohol Spectrum Disorders (CIFASD).
Lipinski RJ, Hammond P, O'Leary-Moore SK, Ament JJ, Pecevich SJ, et al. (2012) Ethanol-Induced Face-Brain Dysmorphology Patterns Are Correlative and Exposure-Stage Dependent. PLoS ONE 7(8): e43067. doi:10.1371/journal.pone.0043067
Research reported in this publication was supported by the National Institute Of Alcohol Abuse and Alcoholism of the National Institutes of Health under Award Numbers AA011605 and AA017124. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Original article: http://www.eurekalert.org/pub_releases/2012-08/uonc-iss082212.php