Modulating Alcohol Effects on the Midface by Vitamin A Derivatives

Objectives: Vitamin A deficiency in the diet is a growing global health problem, a fact supported by the overwhelming evidence from clinical trials of the benefits of low-level vitamin A supplements. Vitamin A is also involved several times during embryogenesis and its metabolism can be impeded by alcohol. Maternal consumption of alcohol, a common teratogen, during unknown pregnancy can result in a spectrum of fetal anomalies, including Fetal Alcohol Syndrome, which characteristics include craniofacial dysmorphism and CNS defects. Although the amount and timing of alcohol intake are major determinants of severity, the lack of strict correlation suggests other important modulators. As alcohol is a competitive inhibitor of vitamin A metabolism, we hypothesized that an increase in dietary vitamin A levels would counteract the effects of alcohol on the fetus. To investigate this, we employed the chick model system and high-resolution tomographic imaging to quantify the impact of these supplements on the developing face. 

Methods:  Fertile eggs were incubated for 18hrs and Hanks-buffered saline solution(HBSS), ethanol(in HBSS), or retinoic acid(RA;in ethanol+HBSS) was injected directly into the yolk. Embryos were allowed to develop to either Hamburger & Hamilton stage 31(~day 7;n≥10 per condition) or HH41(~day 15;n≥12 per condition) and the heads were imaged via optical and X-ray-based tomography, respectively. 3D landmark coordinates were captured and analyzed by geometric morphometric tools(Principal Component Analysis;paired t-test,p≤0.05), and Euclidean Distance Matrix Analysis(SHAPE procedure;90% confidence interval(CI)). 

Results:  Chick embryos exposed to ethanol showed, as expected, significant changes (90% CI) involving the maxilla but not the mandible. Significantly, many of the midfacial changes were prevented by RA supplementation. 

Conclusions:  Alcohol-induced craniofacial changes in the chick were prevented by low-level supplementation with RA. Identification of dietary factors that counteract the effects of teratogens on midface dysmorphism could lead to recommendations for optimal nutrition prior to and during pregnancy. (Supported by UWSOD Alumni Association)