Department of Radiology and Imaging Sciences, IU School of Medicine, Indianapolis, IN 46202, USA.
Alcohol. 2013 Aug;47(5):405-15. doi: 10.1016/j.alcohol.2013.04.005.
Craniofacial bone dysmorphology is an important but under-explored potential diagnostic feature of fetal alcohol spectrum disorders. This study used longitudinal MicroCT 3D imaging to examine the effect of prenatal alcohol exposure on craniofacial bone growth in a mouse model. C57BL/6J dams were divided into 3 groups: alcohol 4.2% v/v in PMI® liquid diet (ALC), 2 weeks prior to and during pregnancy from embryonic (E) days 7-E16; pair-fed controls (PF), isocalorically matched to the ALC group; chow controls (CHOW), given ad libitum chow and water. The MicroCT scans were performed on pups on postnatal days 7 (P7) and P21. The volumes of the neurocranium (volume encased by the frontal, parietal, and occipital bones) and the viscerocranium (volume encased by the mandible and nasal bone), along with total skull bone volume, head size, and head circumference were evaluated using general linear models and discriminant analyses. The pups in the alcohol-treated group, when compared to the chow-fed controls (ALC vs CHOW) and the isocaloric-fed controls (ALC vs PF), showed differences in head size and circumference at P7 and P21, the total skull volume and parietal bone volume at P7, and volume of all the tested bones except nasal at P21. There was a growth trend of ALC < CHOW and ALC < PF. While covarying for gender and head size or circumference, the treatment affected the total skull and mandible at P7 (ALC > CHOW), and the total skull, parietal bone, and occipital bone at P21 (ALC < CHOW, ALC < PF). While covarying for the P7 measures, the treatment affected only the 3 neurocranial bones at P21 (ALC < CHOW, ALC < PF). Discriminant analysis sensitively selected between ALC and CHOW (AUC = 0.967), between ALC and PF (AUC = 0.995), and between PF and CHOW (AUC = 0.805). These results supported our hypothesis that craniofacial bones might be a reliable and sensitive indicator for the diagnosis of prenatal alcohol exposure. Significantly, we found that the neurocranium (upper skull) was more sensitive to alcohol than the viscerocranium (face).
颅面骨畸形是胎儿酒精谱系障碍的一个重要但研究不足的潜在诊断特征。本研究使用纵向 MicroCT 3D 成像技术，在小鼠模型中研究了产前酒精暴露对颅面骨生长的影响。C57BL/6J 孕鼠分为 3 组：酒精 4.2% v/v 加入 PMI®液体饮食（ALC），在妊娠前 2 周和妊娠第 7 天至第 16 天（E）；配对喂养对照组（PF），热量与 ALC 组匹配；自由采食对照组（CHOW），给予自由采食的饲料和水。在产后第 7 天（P7）和第 21 天（P21）对幼鼠进行 MicroCT 扫描。使用通用线性模型和判别分析评估神经颅（由额骨、顶骨和枕骨包裹的体积）和内脏颅（由下颌骨和鼻骨包裹的体积）的体积、总颅骨体积、头大小和头围。与 Chow 喂养对照组（ALC 与 CHOW）和等热量喂养对照组（ALC 与 PF）相比，酒精处理组的幼鼠在 P7 和 P21 时头围和头围大小、P7 时总颅骨体积和顶骨体积以及除鼻骨外所有测试骨的体积均存在差异。存在 ALC < CHOW 和 ALC < PF 的生长趋势。在协变量性别和头围或头围的情况下，处理在 P7 时影响总颅骨和下颌骨（ALC > CHOW），在 P21 时影响总颅骨、顶骨和枕骨（ALC < CHOW，ALC < PF）。在协变量 P7 测量的情况下，处理仅在 P21 时影响 3 个神经颅骨（ALC < CHOW，ALC < PF）。判别分析敏感地区分了 ALC 和 CHOW（AUC = 0.967）、ALC 和 PF（AUC = 0.995）以及 PF 和 CHOW（AUC = 0.805）。这些结果支持我们的假设，即颅面骨可能是产前酒精暴露诊断的可靠和敏感指标。值得注意的是，我们发现神经颅（上颅骨）比内脏颅（面部）对酒精更敏感。
